CN101208306A - Pyrazole compounds and antidiabetes agents containing the same - Google Patents
Pyrazole compounds and antidiabetes agents containing the same Download PDFInfo
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- CN101208306A CN101208306A CNA2006800181941A CN200680018194A CN101208306A CN 101208306 A CN101208306 A CN 101208306A CN A2006800181941 A CNA2006800181941 A CN A2006800181941A CN 200680018194 A CN200680018194 A CN 200680018194A CN 101208306 A CN101208306 A CN 101208306A
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Abstract
A pyrazole compound represented by the general formula (I) or a salt thereof which has a hepatic glycogen phosphorylase inhibitory activity and therefore is useful as a therapeutic or prophylactic agent for diabetes or a pharmacologically salt thereof : wherein the ring Q represents an aryl group or an aromatic heterocyclic group; R<1> represents a hydrogen atom, a halogen atom, a C1-6 alkyl group or a C1-6 alkoxy group; R<2> represents a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group or an azide group; R<3> represents a halogen atom, a hydroxyl group, a C1-6 alkyl group, a halo-C1-6 alkyl group, a C1-6 alkoxy group, an azide group, an amino group, an acylamino group or a C1-6 alkylsulfonylamino group; R<4> and R<5> independently represent a hydrogen atom, a C1-6 alkyl group which may be substituted, a a C3-8 cycloalkyl group, a saturated heterocyclic group which may be substituted, an aryl group which may be substituted, a C7-14 aralkyl group, an aromatic heterocyclic group or the like.
Description
Technical field
The present invention relates to contain and have liver glycogen phosphorylase (liver glycogenphosphorylase) suppresses the treatment of diabetes or the prophylactic compositions of active pyrazole compound and pharmaceutically permissible carrier, have liver glycogen phosphorylase and suppress active new pyrazole compound, and by these treatment of diabetes or prophylactic compositions and other medicament (for example, remedy for hyperlipemia, the treatment of obesity or preventive, Remedies for diabetes, the diabetic complications therapeutical agent, therapeutic agent for hypertension) pharmaceutical composition that is combined to form.
Background technology
Diabetes are that a kind of shortage because of insulin action causes sugar (glucose), lipid, chronic disease that amino acid whose metabolic disturbance caused.Continuing to show hyperglycemia, glycosuria under the untreated situation.
Diabetes roughly are divided into type i diabetes (insulin-dependent diabetes; IDDM) and type ii diabetes (non-insulin-dependent diabetes mellitus (NIDDM); NIDDM), the principal character of described type i diabetes is the hypoinsulinism that causes because of insulin cell is destroyed, described insulin cell destroys because self produces antibody to pancreas islet causes, and described type ii diabetes is because the insulin resistance (resistance) in peripheral tissues such as the insulin secretion function obstacle of pancreas or muscle tissue and the liver causes.Insulin-dependent diabetes is easy to cause ketonemia, oxypathy disease owing to lost insulin secretion function, if do not treat, can cause diabetic coma.Diet or oral hypoglycemic do not have result of treatment, can only adopt Regular Insulin to treat.On the other hand, non-insulin-dependent diabetes mellitus (NIDDM) (NIDDM) though insulin action than standard state a little less than, the proneness that develops into ketonemia, oxypathy disease a little less than, Regular Insulin is not necessary to treatment.About 90-95% among the diabetic subject is the diabetes of non-insulin-dependent.
The diabetic subject can cause the complication such as tiny blood vessels obstruction in neurological disorder, retinopathy, the kidney etc. because hyperglycemia state continues for a long time, and then causes the fatal complication as coronary artery disease or cerebral apoplexy and so on.
At present, as the hypoglycemic agents that uses in order to treat hyperglycemia, insulin preparation, sulfonylurea agent are arranged usually (for example, Glyburide, tolbutamide), the biguanides medicine (for example, N1,N1-Dimethylbiguanide), the medicine that improves insulin resistance (for example, pioglitazone (pioglitazone)), alpha-glucosidase inhibitor (for example, acarbose).
Insulin preparation is the medicament that uses in insulin-dependent diabetes, can guarantee that blood sugar reduces, but they can only pass through drug administration by injection, and might cause hypoglycemia.
But sulfonylurea agent stimulating pancreas β cell promote the endogenous insulin secretion of pancreatic beta cell, and the time of insulin secretion and secretory volume and blood glucose value is irrelevant, depend on time of administration, dosage.Therefore, as side effect, occur owing to the long hypoglycemia that causes of drug treating time through regular meeting.In addition, Alimentary diseases such as poor appetite can appear.The sulfonylurea agent should be forbidden in the patient that serious ketosis or liver or renal tubal dysfunction are arranged.
Biguanide drug is stimulating pancreas β cell not, all can not cause hypoglycemia for healthy people and diabetic subject when it is individually dosed.As the mechanism of action, it is believed that the increase of the sugared usability that is based on the anaerobism glycolysis, to glycogenetic inhibition, to inhibition of the intestinal absorption of sugar etc.As side effect, be easy to generate more serious lactic acidosis disease.
As the medicine that improves insulin resistance (insulin sensitizer) tetrahydrothiazole derivates is arranged, but the tetrahydrothiazole derivates compound can not promote insulin secretion, it can strengthen the effect of Regular Insulin, activate insulin receptor kinase, promote the Sugar intake of peripheral tissues, improve the excessive generation of glycogen etc., but as side effect, can cause chylopoietic disease and oedema etc., in addition, can cause the reduction of erythrocyte number, hematocrite value, hemoglobin concentration and the rising of LDH, this is known.
Alpha-glucosidase inhibitor can postpone digestion, the absorption of carbohydrate class in digestive tube, rise thereby suppress postprandial blood sugar, but it can cause that side effects such as feeling of repletion, borborygmus, diarrhoea are (for example, with reference to non-patent literature 1.)。
As mentioned above, these medicines are owing to can produce some side effect or have invalid patient, and its use is carried out restriction, therefore wish to occur the new hypoglycemic agents of a kind of mechanism of action.
In recent years, the someone has reported NIDDM patient and healthy physiognomy ratio, and the sugar amount that is discharged by liver when going on a hunger strike has increase.Should discharge sugared phenomenon by liver and hint that existence can become the possibility of the target of NIDDM pharmacological agent.
When diabetes situation is in recent years judged, it is generally acknowledged the dysfunction of pancreatic beta cell and discharge excessive sugar very big relation is arranged (for example, with reference to non-patent literature 2 with the morbidity and the development thereof of diabetes by liver.)。The process that is discharged sugar by liver can be expressed as the decomposition of liver starch and this two lines sum of generation of sugar.Someone has reported that there is hyperfunction phenomenon (for example, with reference to non-patent literature 3,4) in the glycogenolysis system of liver under diabetic disease states.In addition, the somebody has reported that by suppressing the decomposition of liver starch healthy people's blood glucose value is (for example, with reference to non-patent literature 5 in the time of can reducing the stimulation of diabetic animal or hyperglycemic-glycogenolytic factor.)。Thus, it has been generally acknowledged that the decomposition of liver starch is hyperfunction relevant with glycosuria morbid state.
On the other hand, oneself knows that the decomposition of this glycogen can pass through liver glycogen phosphorylase catalysis, decomposes by making glycogen (n glucose unit) carry out peroxophosphoric acid, can produce glucose 1-phosphoric acid (G-1-P) and glycogen (n-1 glucose unit).
On this basis, the researchist pair has the Remedies for diabetes of the inhibiting new mechanism of liver glycogen phosphorylase of bigger relation to develop with this glycogenolysis.But, also do not appear at the gratifying medicine in active aspect at present.
In addition, know the liver glycogen phosphorylase inhibitor and produce effect, but in addition, the somebody has reported that it has various action effects as treatment of diabetes medicine or prophylactic agent.
For example, reported that having liver glycogen phosphorylase suppresses active compound and " can be used for treating diabetes, insulin resistance disease, diabetes nerve obstacle, diabetic nephropathy, diabetic retinopathy, cataract, hyperglycemia, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, atheroma arteriosclerosis, tissue ischemia disease, myocardial ischemia disease ".(for example, refer to Patent Document 1.)。
In addition, having liver glycogen phosphorylase, to suppress active compound be effective as the appetite stimulator therapeutical agent with at the therapeutical agent of obesity, in addition, the lipid content that reduces in the blood also is effective, for example, be of value to sick treatment or preventions such as lipidemia unusual (dyslipidemia), hyperglyceridemia, hyperlipidaemia, hyperlipoproteinemia, cardiovascular disease and vascular hypertension.(for example, referring to Patent Document 2).
In addition, reported that the liver glycogen phosphorylase inhibitor is to relating to the disease of glucose metabolism, for example, comprise that diabetes, especially secular complication (for example, retinopathy, neurological disorder, ephrosis and microangiopathy, macroangiopathic) are in the treatment of interior non-insulin-dependent diabetes mellitus (NIDDM) (NIDDM) or prevention effectively.(for example, refer to Patent Document 3.)。
In addition, in the mankind, glycogen phosphorylase is accredited as three kinds of isomer (isoforms), be liver isomer, muscle isomer and brain isomer, these isomer are three kinds of different gene products, they have the homogeny of the aminoacid sequence of 80-83%, in addition, glycogen phosphorylase also is present in the bacterium, and have liver glycogen phosphorylase suppress active compound can be used for the treatment or preventing infection disease, for example, the method for bacillary, fungoid, parasite or viral infection disease produces effect to the treatment and the prevention of above-mentioned infection disease.(for example, referring to Patent Document 4).
Therefore, the liver glycogen phosphorylase inhibitor also can expect to be used as effectively the therapeutical agent of insulin resistance disease, diabetes nerve obstacle, diabetic nephropathy, diabetic retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, atheroma arteriosclerosis, tissue ischemia disease, myocardial ischemia disease except as treatment of diabetes agent and the preventive thereof; Appetite stimulator therapeutical agent and at the therapeutical agent of obesity; Bacillary, fungoid, parasite or viral infection disease etc. are infected the therapeutical agent of disease.
May compare similar compounds with the present invention as liver glycogen phosphorylase inhibitor and structure at present, oneself knows following compound.
WO96/39384 (the flat 10-511687 communique of special table) discloses a kind of compound with indole structure of glycogen phosphorylase inhibitory activity.(referring to Patent Document 5).
(wherein, R
4Be phenylalkyl etc., R
5Be hydrogen atom etc., R
6Be alkoxy carbonyl etc., R
2Be hydrogen atom, R
1, R
10And R
11Be hydrogen atom, halogen atom etc. independently of one another, R
3Be hydrogen atom etc., A is-N=).
As concrete compound, for example, following compound is disclosed.
WO01/94300 A1 discloses the Acylphenylurea derivatives of the treatment effective following general formula of type ii diabetes (I) expression, their preparation method.(referring to Patent Document 6).
(in the above-mentioned general formula (I), A refers to phenyl, the naphthyl that can be replaced by various substituting groups, and R1 and R2 refer to hydrogen atom, alkyl etc., and R3, R4, R5 and R6 refer to hydrogen atom, alkyl etc., X refers to Sauerstoffatom or sulphur atom, and R7 refers to the alkyl that replaced by carboxyl, phenyl, heterocyclic radical etc. etc.)
WO02/096864 A1 discloses the Carboxylamide substituted-phenyl urea derivatives of the treatment effective following general formula of type ii diabetes (I) expression, their preparation method.(referring to Patent Document 7).
(in the above-mentioned general formula (I), A refers to phenyl, the naphthyl that can be replaced by various substituting groups, and R1 and R2 refer to hydrogen atom, halogen atom etc., R3, R4, R5 and R6 refer to hydrogen atom, halogen atom etc., R7 refers to hydrogen atom, alkyl etc., R8 refer to hydrogen atom, can substituted alkyl etc., R9 refers to halogen atom etc.)
WO03/015774 A1 has reported that the derivative shown in the following general formula (I) can be used for treating the disease that causes because of glucokinase (GLK) as type ii diabetes and so on.(referring to Patent Document 8).
(in the above-mentioned general formula (I), m is 0,1 or 2, and n is 0,1,2,3 or 4, and n+m＞0, R
1Be OH independently ,-(CH
2)
1-4OH ,-CH
3-aF
a, halogen, C
1-6Alkyl, phenyl can be by C
1-6The heterocycle that alkyl replaces etc., R
2Be-X-Y, X is selected from-O-Z-,-O-Z-O-Z-, and-C (O) O-Z-,-OC (O) Z-,-S-Z-, the connection base of direct combination etc., Z is direct combination, C
2-6Alkenylenes etc., Y are aryl-Z
1-, heteroaryl-Z
1-, C
1-6Alkyl etc., R
3Be can be by R
7The heterocyclic radical that replaces.)
And, in same document, as R
3Example with concrete compound of pyrazoles skeleton, embodiment GG 2 and 5 in put down in writing following compound.
In addition, same specification sheets has proposed the compound of following general formula (Ib) expression as substance invention.
(wherein, R
1Expression hydroxyl, hydroxyalkyl, fluorinated alkyl, halogen atom, alkoxyl group, alkyl etc., R
2Be-X-Y, X is-O-Z-etc., Y is-the Z1-aryl etc., R
2Do not comprise halogen atom or alkyl.In addition, m is 0,1 or 2, and n is 1,2, or 3, and n+m is 2 or 3.)
From the above, even m maximum just 2, phenyl can not replaced simultaneously by three halogen atoms.
WO03/084922 A1 discloses acyl group-4-carboxyl phenyl urea derivatives of representing as the useful following general formula of antidiabetic drug.(referring to Patent Document 9).
(wherein, R7, R8, R9, R10 are identical or different respectively and refer to hydrogen atom, halogen atom, alkoxyl group etc., R1, R2 refer to hydrogen atom, alkyl etc., R3 refers to hydrogen atom, halogen atom, phenoxy group etc., R4 refers to hydrogen atom, halogen atom, nitro, phenoxy group etc., R5 refers to hydrogen atom, halogen atom, phenoxy group, alkyl etc., and R6 refers to hydrogen atom, halogen atom, phenoxy group, alkyl etc.)
WO03/084923 A1 discloses the acyl group-3-carboxyl phenyl urea derivatives as useful following general formula (I) expression of antidiabetic drug.(referring to Patent Document 10).
(wherein, R7, R8, R9, R10 are identical or different respectively and refer to hydrogen atom, halogen atom, alkoxyl group etc., R1, R2 refer to hydrogen atom, alkyl etc., R3 refers to hydrogen atom, halogen atom, phenoxy group etc., R4 refers to hydrogen atom, halogen atom, nitro, phenoxy group etc., R5 refers to hydrogen atom, halogen atom, phenoxy group, alkyl etc., and R6 refers to hydrogen atom, halogen atom, phenoxy group, alkyl etc.)
WO03/104188 A1 discloses the N-benzoyl urea meat silicate derivative as useful following general formula (I) expression of antidiabetic drug.(referring to Patent Document 11).
(wherein, R7, R8, R9, R10 are identical or different respectively and refer to hydrogen atom, halogen atom, alkoxyl group etc., and R1, R2 refer to hydrogen atom, alkyl etc., and R3, R4, R5, R6 refer to hydrogen atom, halogen atom, alkyl etc., and R11 refers to-OR12 ,-N (R18) is (R19).)
WO2004/007455 A1 discloses the heterocyclic aryl substituted benzene formyl urea derivatives as useful following general formula (I) expression of type ii diabetes curative.(referring to Patent Document 12).
(wherein, R1, R2 refer to hydrogen atom, alkyl, amino etc., and R3, R4 refer to halogen atom, hydroxyl, alkyl, alkoxyl group etc., and R5 refers to hydrogen atom, halogen atom, hydroxyl, alkyl etc., A refers to hydrogen atom, halogen atom, alkyl, alkyl-carbonyl etc., and Het refers to the heterocyclic radical of triazole, tetrazolium, pyrazoles etc.)
WO2004/033416 A2 discloses the carboxyl alkoxyl group substituted acyl carboxyl urea derivatives as useful following general formula (I) expression of type ii diabetes curative.(referring to Patent Document 13).
(wherein, R1 refers to hydrogen atom, alkyl, phenyl etc., and R2 refers to hydrogen atom, alkyl, alkoxyl group etc., and R3 refers to hydrogen atom, halogen atom, alkoxyl group etc., and n refers to the integer of 1-8.)
WO2004/065356 A1 discloses the carbonylamino substituted acyl phenylurea derivative as useful following general formula (I) expression of type ii diabetes curative.(referring to Patent Document 14).
(wherein, R8, R9, R10, R11 refer to hydrogen atom, halogen atom, hydroxyl, nitro, alkoxyl group etc., R1, R2 refer to hydrogen atom, the alkyl that can replace, alkoxyl group etc., R3, R4, R5, R6 refer to hydrogen atom, halogen atom, nitro, phenoxy group, hydroxyl etc., and R7 refers to hydrogen atom, alkyl, cycloalkyl etc.)
In addition, also have several pieces of reports about pyrazole compound with amide substituents.
For example, WO2004/098589 A1 disclose following general formula (I) or (II) expression pyrazole compound 4-bromo-5-(2-chloro-benzoyl-amido)-1H-pyrazole-3-carboxamide derivative.
But these compounds relate to the bradykinin B that is used for the treatment of diseases associated with inflammation
1(bradykininB
1) receptor antagonist.(referring to Patent Document 15).
(wherein, Z ' refers to O, S or NH, and Q refers to N (R
4) (R
5), OH, alkyl etc., R
1Refer to hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic radical, substituted heterocyclic radical etc., R
2, R
3Refer to hydrogen atom, alkyl, substituted alkyl, aryl etc., R
4, R
5Refer to hydrogen atom, alkyl, substituted alkyl, alkoxyl group, cycloalkyl, substituted cycloalkyl, heterocyclic radical, substituted heterocyclic radical etc., X refers to hydrogen atom, halogen atom, alkyl etc.
In addition, as the concrete example of R1, in the 333rd page in this specification sheets, enumerated a plurality of substituting groups, for example, 2-chloro-phenyl-, 2-fluorophenyl, 2-hydroxy phenyl, 2-nitrophenyl etc. particularly, have been put down in writing 2,4 dichloro benzene base, 3,4,5-trifluorophenyl etc.But, according to the record of the 17th page in this specification sheets, preferred R
1Base is 2-chloro-phenyl-, 2-fluorophenyl, 2-(quinoline-8-yl) benzene-1-base or 2-((3-methylbenzene-1-base alkylsulfonyl (sulfanyl)) methyl) benzene-1-base; and about 2-chloro-4; 5-difluorophenyl, 4; 5-two fluoro-2-aminomethyl phenyls, 2; 4-two chloro-5-fluorophenyls etc. had not both had concrete record, did not point out their record yet.)
In the above-mentioned document, as the concrete example of derivative, embodiment discloses compound as described below.But, be the concrete compound of representative with the embodiment of wherein record, as apparent by its title " 4-bromo-5-(2-chloro-benzoyl-amido)-1H-pyrazole-3-carboxamide derivative ", its principal character is R
1Has the substituting group of forming by halogen atom or alkyl for the 2-chloro-phenyl-and on the pyrazoles ring.In addition, purposes also relates to different from described diabetes the useful bradykinin B of anti-inflammatory agent
1(bradykinin B
1) acceptor.
Embodiment 2
Embodiment 6
Embodiment 7
Embodiment 11
Embodiment 16
Embodiment 20
Embodiment 33
Embodiment 34
Embodiment 79
Embodiment 93
Embodiment 121
WO2004/098590 A1 discloses the bradykinin B that a kind of conduct is used for the treatment of diseases associated with inflammation
1(bradykinin B
1) the useful following general formula (I) of receptor antagonist or (II) pyrazole compound of expression.(referring to Patent Document 16).But; as apparent by its title " 4-bromo-5-(2-chloro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (1-(aminocarboxyl) ethyl-1-yl) amide derivatives "; it relates to concrete specific pyrazole compound, i.e. 4-bromo-5-(2-chloro-benzoyl-amido)-1H-pyrazole compound.
(wherein, Z refers to O, S, NH, and Q refers to following general formula.)
That is R,
1The aryl that refer to hydrogen atom, the alkyl that can replace, can replace etc., R
2, R
4Refer to hydrogen atom, the alkyl that can replace, R
3The aryl that refer to hydrogen atom, the alkyl that can replace, can replace etc., R
5, R
6Refer to hydrogen atom, amino acid side chain etc., R
7Finger-NR
bR
c,-OR
bDeng.
In addition, as the concrete example of said derivative, embodiment discloses compound as described below.
WO2004/099155 A2 discloses the bradykinin B that a kind of conduct is used for the treatment of diseases associated with inflammation
1(bradykinin B
1) the useful following general formula (I) of receptor antagonist or (II) substituted pyrazole compounds of expression.(referring to Patent Document 17).
(wherein, Z refers to O, S, NH, R
1Refer to hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl etc., R
2Refer to hydrogen atom, alkyl, substituted alkyl etc., R
3Refer to hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl etc., R
4Refer to aryl, substituted aryl, heteroaryl, substituted heteroaryl, R
5Refer to hydrogen atom, alkyl, substituted alkyl, the alkyl that X refers to hydrogen atom, can replace etc.)
In addition, as the concrete example of said derivative, embodiment discloses compound as described below.
Embodiment 2
Embodiment 6
Embodiment 7
Embodiment 14
WO2004/072060 A1 disclose a kind of to type ii diabetes treatment and prevent useful replacement 3-(benzoyl urea)-thiophene derivant (referring to Patent Document 18).
(wherein, R5 refers to F, Cl or Br, and R1 refers to hydrogen atom, F, Cl or Br, and R2 refers to hydrogen atom, F, Cl, Br, alkyl etc., and R3 refers to hydrogen atom, alkyl etc., and R4 refers to hydrogen atom, alkyl etc.)
WO2004/078743 A1 disclose a kind of to type ii diabetes treatment and prevent useful substituted 3-(benzoylureido) pyridyl-piperidines and-pyrrolidine carboxylic acid derivatives (referring to Patent Document 19).
(wherein, R1, R2 refer to hydrogen atom, F, Cl, and X refers to OH, NH
2, alkoxyl group etc., A, B, D, E refer to CH or N, m refers to 0,1 or 2.)
[non-patent literature 1] JOSLIN ' S DIABETES MELLITUS 13Th Edition, pp.521-522
[non-patent literature 2] Withers D.J., Endocrinology 141; Pp.1917-1921,2000
[non-patent literature 3] Tayek J.A., Am.J.Physiol.270; Pp.E709-E717,1996
[non-patent literature 4] Diraison F., Diabetologa 41; Pp.212-220,1998
[non-patent literature 5] William H.Martin, Proc.Natl.Acad.Sci.USA 95; Pp.1776-1781,1998, Judith L., Abstracts from the ADA 61st Scientific Session
[patent documentation 1] spy opens the 2004-002311 communique
[patent documentation 2] special table 2002-536410 communique
[patent documentation 3] special table 2002-515064 communique
[patent documentation 4] spy opens the 2001-247565 communique
[patent documentation 5] WO96/39384 (the flat 10-511687 communique of special table)
[patent documentation 6] WO01/94300A1
[patent documentation 7] WO02/096864A1
[patent documentation 8] WO03/015774A1
[patent documentation 9] WO03/084922A1
[patent documentation 10] WO03/084923A1
[patent documentation 11] WO03/104188A1
[patent documentation 12] WO2004/007455A1
[patent documentation 13] WO2004/033416A2
[patent documentation 14] WO2004/065356A1
[patent documentation 15] WO2004/098589A1
[patent documentation 16] WO2004/098590A1
[patent documentation 17] WO2004/099155A2
[patent documentation 18] WO2004/072060A1
[patent documentation 19] WO2004/078743A1
At present the target of the most remedy for diabetes that uses is these four kinds in pancreas (promotion insulin secretion), tip (improving the tolerance of Regular Insulin), small intestine (hindering sugar absorbs) and a Regular Insulin.But, in recent years, wish to develop a kind of remedy for diabetes based on new binding mode, and just noticeable based on exploitation to the remedy for diabetes of the inhibition of liver glycogen phosphorylase.But, aspect active, also do not meet the demands.In addition, can't be satisfactory for oral absorption and metabolic stability aspect.
Therefore, urgent wish to develop a kind of remedy for diabetes with in the past mutually specific activity stronger, be free from side effects the liver glycogen phosphorylase inhibitor of while oral absorption and metabolic stability excellence.
Summary of the invention
The purpose of this invention is to provide a kind of remedy for diabetes with in the past mutually specific activity stronger, be free from side effects and the liver glycogen phosphorylase inhibitor of oral absorption and metabolic stability excellence.
In addition, to provide a kind of be insulin resistance disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, atheroma arteriosclerosis, the tissue ischemia disease of effective constituent, the therapeutical agent of myocardial ischemia disease with the liver glycogen phosphorylase inhibitor to another purpose; Appetite stimulator therapeutical agent and at the therapeutical agent of obesity; Bacillary, fungoid, parasite or viral infection disease etc. are infected the therapeutical agent of disease.
The present invention is in view of above-mentioned problem, to have liver glycogen phosphorylase and suppress active useful remedy for diabetes and carried out wholwe-hearted research in order to explore, the pyrazole compound that found that following general formula (I) expression has strong liver glycogen phosphorylase inhibition activity, has so far finished the present invention.
More detailed theing contents are as follows stated shown in the 1-57.
1. treatment of diabetes or prophylactic compositions, it contains admissible salt and pharmaceutically permissible carrier on the pyrazole compound of following general formula (I) expression or its pharmacology.
[wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4And R
5Identical or different respectively, expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(6) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(7) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52。
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(8) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base (oxo) or sulfenyl (thioxo) replacement.
(9) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(10) C
7-14Aralkyl
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom
F3. cyano group
F4. hydroxyl
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(11) be selected from the C of identical or different more than one substituting group replacement that condenses the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent and these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6Identical or different-individual above the substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be that hydrogen atom, five yuan or hexavalent are monocyclic
Saturated heterocyclyl or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.
In addition, above-mentioned R
4And R
5(wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring can to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。]
2. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 1, it contains admissible salt and pharmaceutically permissible carrier on the pyrazole compound of following general formula (I) expression or its pharmacology.
[wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-4Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4Expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R4
11)(R4
11’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(6) C
3-8Cycloalkyl C
1-6Alkyl; Perhaps
(7) aryl;
R
5Expression
(1) can be selected from the C that the more than one substituting group of following group of B replaces
1-6Alkyl;
[group B]
B1. hydroxyl,
B2.C
1-6Alkoxyl group,
B3. -N(R
51)(R
51’)、
(wherein, R
51And R
51' identical or different, expression hydrogen atom or C
1-6Alkyl, R
51And R
51' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
And
B4.-CO-N(R
511)(R
511’)、
(wherein, R
511And R
511' identical or different, expression hydrogen atom or C
1-6Alkyl, R
511And R
511' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
(2) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(3) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(4) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52。
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(5) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53With
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.
(6) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(7) C
7-14Aralkyl
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom
F3. cyano group
F4. hydroxyl
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(8) C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6Alkyl or condensed the C that the aromatic heterocycle of formation replaces by these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The identical or different more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.In addition, above-mentioned R
4And R
5(wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring can to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。]
3. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 1, wherein pyrazole compound is the pyrazole compound of following general formula (II ') expression.
(wherein, R
1, R
2, R
3, R
4And R
5With above-mentioned 1 synonym.)
4. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 1, wherein pyrazole compound is the pyrazole compound of following general formula (II) expression.
(wherein, R
4And R
5With above-mentioned 1 synonym, R
1aExpression halogen atom or hydrogen atom, R
2aThe expression halogen atom, R
3aExpression halogen atom or C
1-6Alkyl.)
5. treatment of diabetes or prophylactic compositions, the wherein R of record in above-mentioned 4
1aExpression hydrogen atom or fluorine atom, R
2aExpression fluorine atom or chlorine atom, R
3aExpression chlorine atom or C
1-6Alkyl.
6. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 5, wherein pyrazole compound is the pyrazole compound of following general formula (III) expression.
(wherein, R
4And R
5With above-mentioned synonym.)
7. the treatment of diabetes of putting down in writing among the above-mentioned 2-6 or prophylactic compositions, wherein R
4Be to be selected from following group base.
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A ' replaces
1-6Alkyl;
[group A ']
A ' 1. hydroxyl,
A ' 2.C
1-4Alkoxyl group,
A’3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-4Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 4. phenyl,
A ' 5. five yuan or the monocyclic aromatic heterocycle of hexavalent,
A’6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-4Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 7. carboxyl and
A ' 8.C
1-4Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl; And
(6) C
3-8Cycloalkyl C
1-4Alkyl;
8. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5Be C
1-6Alkyl.
9. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5Be C
3-8Cycloalkyl (this C
3-8Cycloalkyl can be selected from hydroxyl, carboxyl or C
1-6The identical or different more than one substituting group of alkoxy carbonyl replaces).
10. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5Be C
3-8Cycloalkyl C
1-6Alkyl.
11. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5Be can be selected from acyl group and-CO-(Alk)
n-COOR
52(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n be 0 or the integer of 1-3) more than one substituting group five yuan or the monocyclic saturated heterocyclyl of hexavalent replacing.
12. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5It is the phenyl that can be selected from the more than one substituting group replacement of following group of D '.
[group D ']
D ' 1. can be by the C of carboxyl substituted
1-4Alkyl,
D’2.-CO-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-4Alkyl or C
1-4Alkyl sulphonyl.)
D’3.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-4Alkyl, C
1-4Alkyl-carbonyl oxygen base C
1-4Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-4Alkyl.)
And
D ' 4. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
13. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5Be C
7-14Aralkyl (this C
7-14The more than one substituting group that the aryl moiety of aralkyl can be selected from following group of F ' replaces).
[group F ']
F ' 1.C
1-6Alkyl,
F ' is halogen atom 2.
F ' is cyano group 3.
F ' is hydroxyl 4.
F ' 5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F ' is halo C 6.
1-6Alkyl,
F ' 7. carboxyl,
F ' 8.C
1-6Alkoxy carbonyl,
F’9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f '
1-6Alkyl.)
[group f ']
F ' 1. amino,
The 2. single C of f '
1-6Alkylamino,
F ' is two C 3.
1-6Alkylamino,
F ' is carboxyl 4.
F ' 5.C
1-6Alkoxy carbonyl,
F ' is hydroxyl 6.
And
F ' 7. has five yuan or the monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms.
F’10. -N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F’11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-4Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-4Alkyl.)
12. 5 yuan of F ' or the monocyclic aromatic heterocycle of hexavalent,
And
F ' 13. methylene radical dioxy bases or ethylidene dioxy base.
14. the treatment of diabetes of putting down in writing among the above-mentioned 2-7 or prophylactic compositions, wherein R
5The C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6(this aromatic heterocycle can be replaced by the more than one substituting group of following group of G ' alkyl.)
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' is amino 2.
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G’7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
15. the treatment of diabetes of putting down in writing among the above-mentioned 2-6 or prophylactic compositions, wherein R
4And R
5(this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。
16. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 2, wherein pyrazole compound is the pyrazole compound of following general formula (IV) expression.
(wherein, R
4With above-mentioned 2 synonyms, R
X1, R
X2, R
X3Respectively identical or different, the expression hydrogen atom or be selected from following group of F " substituting group, m represents 0 or the integer of 1-2.)
[group F "]
F " 1.C
1-6Alkyl,
F " 2. halogen atom
F " 3. cyano group
F " 4. hydroxyl
F " 5. can be selected from carboxyl and C
1-4The C that the more than one substituting group of alkoxy carbonyl replaces
1-4Alkoxyl group,
F " 6. halo C
1-6Alkyl,
F " 7. carboxyl,
F " 8.C
1-6Alkoxy carbonyl,
F”9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from following group of f " the C that replaces of more than one substituting group
1-6Alkyl.)
[group f "]
F " 1. amino,
F " 2. single C
1-6Alkylamino,
F " 3. two C
1-6Alkylamino,
F " 4. carboxyl
F " 5.C
1-6Alkoxy carbonyl,
F " 6. hydroxyl
And
F " 7. have five yuan or a monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms.
F”10. -N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F”11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-6Alkyl.)
F " 12. 5 yuan or the monocyclic aromatic heterocycle of hexavalent,
And
F " 13. methylene radical dioxy bases or ethylidene dioxy base.
17. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 2, wherein pyrazole compound is the pyrazole compound that following logical formula V is represented.
(wherein, R
4With above-mentioned 2 synonyms, ring Het represents five yuan or the monocyclic aromatic heterocycle of hexavalent, R
Y1, R
Y2, R
Y3Respectively identical or different, expression hydrogen atom or be selected from the substituting group of following group of G ', the integer of m ' expression 0 or 1 one 2.)
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' is amino 2.
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G’7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
18. the treatment of diabetes or the prophylactic compositions of record wherein encircle Het and represent pyridine ring, triazole ring or azoles ring in above-mentioned 17.
19. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 18, wherein pyrazole compound is the pyrazole compound of following general formula (VI) expression.
(wherein, R
4, R
Y1, R
Y2, R
Y3, m ' and above-mentioned synonym.)
20. the treatment of diabetes or the prophylactic compositions of record in above-mentioned 2, wherein admissible salt is selected from following group on pyrazole compound or its pharmacology.
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides 3/2 hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides L-(+)-tartrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl) acid amides dihydrochloride
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diethylamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-cyclohexyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenoxy group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two fluoro-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-trifluoromethyl-benzamide
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-the benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-tertiary butyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-dimethylamino-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-sec.-propyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-6-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-oxyethyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(pyridin-3-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1H-benzimidazolyl-2 radicals-ylmethyl)-acid amides dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-ritalin,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-methyl propionate
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-pair-(2-acetoxyl group ethyl)-amino-ethyl formamyl]-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-hydroxyl-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-{2-[(2-acetoxyl group ethyl)-(2-hydroxyethyl)-amino]-the ethylamino formyl radical }-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-benzimidazolyl-2 radicals-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzothiazole-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-pyrroles-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,4-dimethoxy-pyridine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (the 5-tertiary butyl-thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-2-phenyl-2H-[1,2,3] triazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(tert-butoxycarbonyl-amino)-methyl-pyridine-2-ylmethyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-methyl-2-(morpholine-4-yl)-thiazole-5-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides 3/2 hydrochloride 1/2 hydrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethoxy carbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibenzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (cyano group-phenyl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hydroxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl amide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid allyl group-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(1-methyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [(3,4-methylenedioxyphenyl base)-methyl]-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(4-hydroxyl-butyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibutyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid is two-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopentyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(3-methoxyl group-propyl group)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-oxyethyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-isopropoxy-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-propoxy--ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethyl-propyl group)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-tert-butoxycarbonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethanoyl-piperidin-4-yl)-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-methylsulfonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-ethoxalyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxalic acid-acyl group (oxalo)-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1,1-dioxy-six hydrogen-1 λ
6-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxygen-six hydrogen-1 λ
4-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid propyl group-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-formamyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-oxalic acid one acyl group-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-carboxyl ethanoyl-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(2-carboxypropanoyl)-piperidin-4-yl]-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclobutyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl methyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-carboxyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-ethoxy carbonyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1H-pyrazol-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridine-2-base-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-3-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-4-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid pyrazine-2-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-methyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-hydroxyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-methyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-hydroxyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two bromo-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethyl-2-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-ethyl-4-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ([2,2 '] dithio phenyl-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methoxyl group-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl- azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hexyl-4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-thiene-3-yl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-2-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-4-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-hexyl-2-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenyl-thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenoxy group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(pyridin-3-yl)-ethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (xenyl-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1R, 2S)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1S, 2R)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-2-pyridone-3-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-piperazine-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenylacetamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-styroyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroisoquinoline-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroquinoline-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid amyl group-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diphenyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridine-2-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (furans-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxycarbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-trifluoromethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-dimethylamino-ethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,6-dimethoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxycarbonyl methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-carboxyl methoxyl group-benzamide,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-difluoro benzoyl amino)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides,
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid sec.-propyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (ethoxy carbonyl-methyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (carboxyl-methyl)-phenyl-acid amides,
5-(2-chloro-4-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-oxygen-2-(piperidines-1-yl)-ethyl]-phenyl-acid amides,
5-(5-fluoro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-methoxyl group-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-ethyl)-phenyl-acid amides,
5-(2-fluoro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-2,6-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-3-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethylamino formyl radical methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isobutyl--phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxycarbonyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-ethoxy carbonyl-propyl group)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-carboxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-propyl group)-phenyl-acid amides,
5-(2-hydroxyl-4-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-hydroxy-5-methyl oxygen base-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-hydroxyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-phenyl-acid amides,
5-(2,5-dimethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-pyridine-2-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,6-two chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl-phenyl)-acid amides,
5-(2-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-6-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-pyridine-4-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(morpholine-4-base formamyl)-benzamide dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-acetic acid sodium salt,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-propionic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(morpholine-4-base formamyl)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[2-(morpholine-4-yl)-ethylamino formyl radical]-the pyridin-4-yl methyl }-the acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-base formamyl)-pyridin-4-yl methyl]-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides 1/2 vitriol
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-amino methyl-pyridine-2-ylmethyl)-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dimethanesulfonate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(morpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-diethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-2-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 5-methyl-pyrazine-2-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-methylpiperazine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-dimethylamino-piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(tetramethyleneimine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid carbamyl ylmethyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formamyl-phenyl)-methyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(4-methylamino formyl radical-phenyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formyl-dimethylamino-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(4H-[1,2,4] triazole-3-yl)-phenyl]-amide hydrochloride,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl] acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(N-hydroxyl carbamimidoyl)-phenyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-2,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2,2-dimethyl-propionyl oxygen base)-methoxycarbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[N-(methoxyl group-thiocarbonyl oxygen base)-carbamimidoyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-sulfo--4,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-4,5-dihydro-[1,2,4] thiadiazoles-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(cyclohexyl oxygen base-ketonic oxygen base)-ethoxy carbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-thiazol-2-yl)-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-cyano group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(toluene-4-sulfuryl amino)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-6-fluoro-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-4,5-two fluoro-benzamide hydrochloride salts,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (7-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-4H-quinazoline-3-yl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-2-methyl isophthalic acid, 4-dihydro-2H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(N-hydroxyl carbamimidoyl)-pyridin-4-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(5-oxygen-4,5-dihydro-[1,2,4] diazole-3-yl)-pyridin-4-yl methyl]-acid amides,
4-{[5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,6-two chloro-5-fluoro-pyridine-3-carbonylaminos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-benzo [b] thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-benzoyl-amido-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-phenyl acetyl amino-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-amino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methylsulfonyl amino-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-acetylamino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3,4,5-three chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(1H-tetrazolium-5-yl)-pyridin-4-yl methyl]-acid amides and
1H-pyrazoles-3,5-dicarboxylic acid 3-benzamide 5-[(2,4-two chloro-phenyl)-acid amides].
21. a medicine, it forms by the treatment of diabetes that will put down in writing among the above-mentioned 1-20 or prophylactic compositions and other Remedies for diabetes or preventive combination.
22. the medicine of record in above-mentioned 21, wherein other Remedies for diabetes or preventive are insulin preparation (injections), low molecule oral insulin agent, sulfonylurea receptor stimulant (SU agent), the non-sulfonylurea insulin secretion stimulators, the agent of potassium dependency ATP (KATP) access portal, the α alpha-glucosidase inhibitors, the αDian Fenmei inhibitor, insulin sensitivity enhancer, low molecule tGLP-1 receptor stimulant, the tGLP-1 peptide analogs, DPP IV (DPP-IV) inhibitor, glucagon receptor antagonist, glucocorticoid receptor antagonists, the biguanides agent, the SGLUT inhibitor, fructose-1,6-bisphosphatase (FBPase) inhibitor, Glycogen Synthase kinase 3 (GSK-3) inhibitor, phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, protein tyrosine phosphatase esterase IB (PTPase 1B) inhibitor, inositol monophosphate esterase (SHIP2) inhibitor that contains the SH2 zone, glycogen phosphorylase (GP) inhibitor, glucokinase activators, the GPR40 receptor stimulant, pyruvic dehydrogenase kinase (PDHK) inhibitor, glutamine: fructose-6-phosphate transaminase (GFAT) inhibitor, antioxidant; Nitric oxide scavengers, carnitine palmityl transferase 1 (camitine palmitoyltransferase, CPT-1) inhibitor, growth releasing factor (GHRF), triacylglycerol lipase (hormone-sensitive lipase) inhibitor, PPAR γ receptor stimulant, PPAR γ receptor antagonist, PPAR α/γ receptor stimulant, AMP-sensitization protein kinase (AMPK) activator, adiponectin receptor stimulant or β
3Adrenoceptor agonists.
23. the medicine of record in above-mentioned 21 or 22, wherein other Remedies for diabetes or preventive are Regular Insulin, tolbutamide, glyclopyramide, tsiklamid (acetohexamide), P-607, glybuzole, Glyburide, gliclazid, gsh, mitiglinide, repaglinide, nateglinide, voglibose, acarbose, miglitol, rosiglitazone maleate, Walaphage, U-72107A or Ziavetine.
24. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the above-mentioned 1-20 or prophylactic compositions and other diabetic complications therapeutical agent or preventive.
25. the medicine of record in above-mentioned 24, wherein other diabetic complications therapeutical agent or preventive are protein kinase β (PKC β) inhibitor, angiotensin II receptor antagonists, aldose reductase inhibitor, angiotensin-converting enzyme (ACE) inhibitor, saccharification final product (AGE) generation inhibitor, neuropathy remedies or diabetic nephropathy therapeutical agent.
26. the medicine of record in above-mentioned 24 or above-mentioned 25, wherein other diabetic complications therapeutical agent or preventive are epalrestat, mexiletine hydrochloride or hydrochloric acid imidapril.
27. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the above-mentioned 1-20 or prophylactic compositions and other remedy for hyperlipemia or preventive.
28. the medicine of record in above-mentioned 27, wherein other remedy for hyperlipemia is fibrate class medicament (a PPAR α receptor stimulant), the PPAR delta receptor agonist, microsomal triglyceride transfer protein (MTP) inhibitor, cholesteryl ester transfer protein (CETP) inhibitor, statin class medicament (HMG-CoA reductase inhibitor), anionite-exchange resin, probucol, nicotinic acid class medicament, plant sterol, apolipoproteins-A1 (Apo-A1) inductor, lipoprotein lipase (LPL) activator, the endodermis lipase inhibitor, ezetimibu, ibat inhibitor, inhibitor for squalene synthetic enzyme, the ACAT inhibitor, the lxr receptor agonist, the FXR receptor stimulant, FXR receptor antagonist or adenosine A 1 agonist.
29. the medicine of record in above-mentioned 27 or above-mentioned 28, wherein other remedy for hyperlipemia is clofibrate, bezafibrate, fenofibrate, lovastatin, Simvastatin, Pravastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin, Cerivastatin, Colestyramine, courage ammonium fat, tocopheryl nicotinate, nicomol, pentaerythritol tetranicotinate, stigmasterol or γ orizanol disappear.
30. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the above-mentioned 1-20 or prophylactic compositions and other anti-obesity therapeutical agent or preventive.
31. the medicine of record in above-mentioned 30, wherein other anti-obesity therapeutical agent or preventive are the leptin preparations; pancreatic lipase inhibitor; the norepinephrine serotonin reuptake inhibitors; the cannabinoid receptor antagonist; monoamine re-uptake inhibitor; diacylglycerol acyltransferase (DGAT) inhibitor; glucose dependency insulin secretion promotes polypeptide (GIP) receptor antagonist; the leptin receptor stimulant; bombasin receptor subtype 3 (BRS-3) agonist; the perilipin inhibitor; acetyl-CoA carboxylase 1 (ACC1) inhibitor; acetyl-CoA carboxylase 2 (ACC2) inhibitor; fatty acid synthase inhibitor; sn-1-acyl group-glycerol-3-phosphate acyltransferase (AGPAT) inhibitor; pancreatic phospholipase A2 (pPLA2) inhibitor; melanocortin (MC) receptor stimulant; neuropeptide Y 5 (NPY5) receptor antagonist; Uncoupling Proteins (UCP) inductor or activator; CPT1 (CPT-1) activator; CCK1 (CCKA) agonist; ciliary neurotrophic factor (CNTF); the CRF2 agonist; neuropeptide Y 2 (NPY2) receptor antagonist; neuropeptide tyrosine 4 (NPY4) receptor antagonist; the Thyroid Hormone Receptors beta-agonists; the growth hormone; the atp citrate lyase inhibitors; 5-HT6 antagonist or 5-HT2C agonist.
32. the medicine of record in above-mentioned 30 or above-mentioned 31, wherein other anti-obesity therapeutical agent or preventive are leptin, orlistat, sibutramine, rimonabant or Mazindol.
33. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the above-mentioned 1-20 or prophylactic compositions and other therapeutic agent for hypertension or preventive.
34. the medicine of record in above-mentioned 33, wherein other therapeutic agent for hypertension or preventive are thiazide diuretics, the similar diuretic(s) of thiazides, loop diuretic, K retentivity diuretic(s), Beta receptor blockers, α, Beta receptor blockers, alpha blocker, the central sympathetic inhibitor, tip sexual intercourse sense nerous sedative (Radix Rauvolfiae preparation), Ca antagonist (benzothiazepin class), Ca antagonist (dihydropyridines), vasodilator, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor antagonists, the nitric acid agent, endothelin ETA receptor antagonist, the endothelin-converting enzyme inhibitor; Neprilysin inhibitor, prostaglandin(PG); Prostanoid FP agonist, hypertension fibrinogen inhibitor, NOS3 express intensifying factor; Prostacyclin analogue, Phosphodiesterase V (PDE5A) inhibitor, prostacyclin analogue or aldosterone antagonist.
35. the medicine of record in above-mentioned 33 or above-mentioned 34, wherein other therapeutic agent for hypertension or preventive are Zestoretics, trichloromethiazide, the Wyovin Zestoretic, the sulphonamide chroman, indapamide, tripamide, chlortalidone, Mefrusal, furosemide, antisterone, triamterene, Target, the bisoprolol fumarate, the hydrochloric acid betaxolol, bevantolol hydrochloride, metoprolol tartrate, Acebutolol, Celiprolol Hydrochorid, nipradolol, N-696, nadolol, propranolol hydrochloride, the hydrochloric acid indenolol, carteolol hydrochloride, pindolol, pindolol continues releasing agent, Betriol (Boehringer,Ing.), penbutolol sulfate, bopindolol malonate, amosulalol hydrochloride, hydrochloric acid arotinolol, carvedilol, labetalol hydrochloride, urapidil, Vasocard, the methylsulfonic acid element, E-643, PRAZOSINI HYDROCHLORIDE, phentolamine mesilate, Tenso-Timelets, guanidine hydrochloride method is new, guanabenz acetate, methyldopa, serpentine, rescinnamine, Phenylsulfonic acid A Muluohe, Aranidipine, efonidipine, cilnidipineb, nicardipine hydrochloride, nisoldipine, nitrendipine, nifedipine, nifedipine continues releasing agent, nilvadipine, Bamidipine Hydrochloride, felodipine, KW-3049, CV-4093, Azelnidipine, diltiazem hydrochloride, hydrazine hydrochloride, hydrochloric acid todoralazine, budralazine, cadralazine, captopril, enalapril maleate, alacepril, delapril hydrochloride, Yipingshu, lisinopril, benazepril hydrochloride, the hydrochloric acid imidapril, hydrochloric acid tamocapril, quinapril hydrochloride, Trolapril, perindoprilerbumine, candesartan cilexetil, valsartan, telmisartan, olmesartan medoxomil, sodium nitroprusside, perhaps nitroglycerine.
36. admissible salt on the pyrazole compound of following general formula (I) expression or its pharmacology.
[wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4And R
5Identical or different respectively, expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(6) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(7) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52。
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(8) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
(9) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
(10) C
7-14Aralkyl
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, represent hydrogen atom or C respectively
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(11) be selected from the C of identical or different more than one substituting group replacement that condenses the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent and these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.In addition, above-mentioned R
4And R
5(this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring can to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。]
37. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 36, it is represented with following general formula (I).
[wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4Expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(6) C
3-8Cycloalkyl C
1-6Alkyl; Perhaps
(7) aryl;
R
5Expression
(1) can be selected from the C that the more than one substituting group of following group of B replaces
1-6Alkyl;
[group B]
B1. hydroxyl,
B2.C
1-6Alkoxyl group,
B3.-N(R
51)(R
51’)、
(wherein, R
51And R
51' identical or different, expression hydrogen atom or C
1-6Alkyl, R
51And R
51' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
And
B4.-CO-N(R
511)(R
511’)、
(wherein, R
511And R
511' identical or different, expression hydrogen atom or C
1-6Alkyl, R
511And R
511' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
(2) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(3) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(4) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52。
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(5) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
(6) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, this aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(7) C
7-14Aralkyl
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl,
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(8) C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6Alkyl or condensed the C that the aromatic heterocycle of formation replaces by these aromatic heterocycles and phenyl ring
1-6Alkyl;
(the more than one substituting group that this aromatic heterocycle can be selected from following group of G replaces.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino,
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.In addition, above-mentioned R
4And R
5(wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring can to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。]
38. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 36, it is represented with following general formula (II ').
(wherein, R
1, R
2, R
3, R
4And R
5With above-mentioned 36 synonyms.)
39. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 36, it is represented with following general formula (II).
(wherein, R
4And R
5With above-mentioned 36 synonyms, R
1aExpression halogen atom or hydrogen atom, R
2aThe expression halogen atom, R
3aExpression halogen atom or C
1-6Alkyl.)
40. admissible salt, wherein R on the pyrazole compound of putting down in writing in above-mentioned 39 or its pharmacology
1aExpression hydrogen atom or fluorine atom, R
2aExpression fluorine atom or chlorine atom, R
3aExpression chlorine atom or C
1-6Alkyl.
41. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 40, wherein pyrazole compound is the pyrazole compound of following general formula (III) expression.
(wherein, R
4And R
5With above-mentioned 37 synonyms.)
42. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-41 or its pharmacology
4Be to be selected from following group base.
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A ' replaces
1-6Alkyl;
[group A ']
A ' 1. hydroxyl,
A ' 2.C
1-4Alkoxyl group,
A’3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-4Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 4. phenyl,
A ' 5. five yuan or the monocyclic aromatic heterocycle of hexavalent,
A’6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-4Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 7. carboxyl and
A ' 8.C
1-4Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl; And
(6) C
3-8Cycloalkyl C
1-4Alkyl;
43. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5Be C
1-6Alkyl.
44. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5Be C
3-8Cycloalkyl (this C
3-8Cycloalkyl can be selected from hydroxyl, carboxyl or C
1-6The more than one substituting group of alkoxy carbonyl replaces).
45. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5Be C
3-8Cycloalkyl C
1-6Alkyl.
46. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5Be can be selected from acyl group and-CO-(Alk)
n-COOR
52(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n be 0 or the integer of 1-3) more than one substituting group five yuan or the monocyclic saturated heterocyclyl of hexavalent replacing.
47. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5It is the phenyl that can be selected from the more than one substituting group replacement of following group of D '.
[group D ']
D ' 1. can be by the C of carboxyl substituted
1-4Alkyl,
D’2.-CO-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-4Alkyl or C
1-4Alkyl sulphonyl.)
D’3.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-4Alkyl, C
1-4Alkyl-carbonyl oxygen base C
1-4Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-4Alkyl.)
And
D ' 4. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
48. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5Be C
7-14Aralkyl (this C
7-14The more than one substituting group that the aryl moiety of aralkyl can be selected from following group of F ' replaces.)
[group F ']
F ' 1.C
1-6Alkyl,
F ' 2. halogen atom,
F ' 3. cyano group,
F ' 4. hydroxyl,
F ' 5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F ' is halo C 6.
1-6Alkyl,
F ' 7. carboxyl,
F ' 8.C
1-6Alkoxy carbonyl,
F’9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f '
1-6Alkyl.)
[group f ']
F ' 1. amino,
The 2. single C of f '
1-6Alkylamino,
F ' is two C 3.
1-6Alkylamino,
F ' is carboxyl 4.
F ' 5.C
1-6Alkoxy carbonyl,
F ' is hydroxyl 6.
And
F ' 7. has five yuan or the monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms.
F’10. -N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F’11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-4Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-4Alkyl.)
12. 5 yuan of F ' or the monocyclic aromatic heterocycle of hexavalent,
And
F ' 13. methylene radical dioxy bases or ethylidene dioxy base.
49. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-42 or its pharmacology
5The C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6Alkyl (the more than one substituting group that this aromatic heterocycle can be selected from following group of G ' replaces).
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' is amino 2.
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G’7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
50. admissible salt, wherein R on the pyrazole compound of putting down in writing among the above-mentioned 37-41 or its pharmacology
5And R
4(this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring to form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)。
51. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 37, wherein pyrazole compound is the pyrazole compound of following general formula (IV) expression.
(wherein, R
4With above-mentioned 37 synonyms, R
X1, R
X2, R
X3Respectively identical or different, the expression hydrogen atom or be selected from following group of F " substituting group, m represents 0 or the integer of 1-2.)
[group F "]
F " 1.C
1-6Alkyl,
F " 2. halogen atom
F " 3. cyano group
F " 4. hydroxyl
F " 5. can be selected from carboxyl and C
1-4The C that the more than one substituting group of alkoxy carbonyl replaces
1-4Alkoxyl group,
F " 6. halo C
1-6Alkyl,
F " 7. carboxyl,
F " 8.C
1-6Alkoxy carbonyl,
F”9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from following group of f " the C that replaces of more than one substituting group
1-6Alkyl.)
[group f "]
F " 1. amino,
F " 2. single C
1-6Alkylamino,
F " 3. two C
1-6Alkylamino,
F " 4. carboxyl
F " 5.C
1-6Alkoxy carbonyl,
F " 6. hydroxyl
And
F " 7. have five yuan or a monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms.
F”10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F”，11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, represent hydrogen atom or C respectively
1-6Alkyl.)
F " 12. 5 yuan or the monocyclic aromatic heterocycle of hexavalent,
And
F " 13. methylene radical dioxy bases or ethylidene dioxy base.
52. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 37, wherein pyrazole compound is the pyrazole compound that following logical formula V is represented.
(wherein, R
4With above-mentioned synonym, ring Het represents five yuan or the monocyclic aromatic heterocycle of hexavalent, R
Y1, R
Y2, R
Y3Respectively identical or different, expression hydrogen atom or be selected from the substituting group of following group of G ', the integer of m ' expression 0 or 1-2.)
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' is amino 2.
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G’7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
53. admissible salt on the pyrazole compound of record or its pharmacology wherein encircles Her and represents pyridine ring, triazole ring or azoles ring in above-mentioned 52.
54. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 53, wherein pyrazole compound is the pyrazole compound of following general formula (VI) expression.
(wherein, R
4, R
Y1, R
Y2, R
Y3, m ' and above-mentioned synonym.)
55. admissible salt on the pyrazole compound of record or its pharmacology in above-mentioned 37, wherein admissible salt is selected from following group on pyrazole compound or its pharmacology.
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides 3/2 hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides-p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides L-(+)-tartrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl) acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diethylamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-cyclohexyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenoxy group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two fluoro-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-the benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-tertiary butyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-dimethylamino-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-sec.-propyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-6-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-oxyethyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(pyridin-3-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1H-benzimidazolyl-2 radicals-ylmethyl)-acid amides dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-ritalin,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-methyl propionate
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-pair-(2-acetoxyl group ethyl)-amino-ethyl formamyl]-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-hydroxyl-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-{2-[(2-acetoxyl group ethyl)-(2-hydroxyethyl)-amino]-the ethylamino formyl radical }-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-benzimidazolyl-2 radicals-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzothiazole-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-pyrroles-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,4-dimethoxy-pyridine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (the 5-tertiary butyl-thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-2-phenyl-2H-[1,2,3] triazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(tert-butoxycarbonyl-amino)-methyl-pyridine-2-ylmethyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-methyl-2-(morpholine-4-yl)-thiazole-5-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides 3/2 hydrochloride 1/2 hydrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethoxy carbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibenzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (cyano group-phenyl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hydroxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl amide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid allyl group-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(1-methyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [(3,4-methylenedioxyphenyl base)-methyl]-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(4-hydroxyl-butyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibutyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid is two-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopentyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(3-methoxyl group-propyl group)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-oxyethyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-isopropoxy-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-propoxy--ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethyl-propyl group)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-tert-butoxycarbonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethanoyl-piperidin-4-yl)-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-methylsulfonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-ethoxalyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxalic acid-acyl group-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1,1-dioxy-six hydrogen-1 λ
6-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxygen-six hydrogen-1 λ
4-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid propyl group-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-formamyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-oxalic acid one acyl group-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-carboxyl ethanoyl-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(2-carboxypropanoyl)-piperidin-4-yl]-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclobutyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl methyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-carboxyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-ethoxy carbonyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1H-pyrazol-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridine-2-base-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-3-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-4-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid pyrazine-2-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-methyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-hydroxyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-methyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-hydroxyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two bromo-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethyl-2-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-ethyl-4-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ([2,2 '] dithio phenyl-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methoxyl group-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl- azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hexyl-4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-thiene-3-yl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-2-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-4-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-hexyl-2-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenyl-thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenoxy group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(pyridin-3-yl)-ethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (xenyl-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1R, 2S)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1S, 2R)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-2-pyridone-3-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-piperazine-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid styroyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-styroyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroisoquinoline-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroquinoline-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid amyl group-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diphenyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridine-2-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (furans-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxycarbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-trifluoromethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-dimethylamino-ethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,6-dimethoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxycarbonyl methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-carboxyl methoxyl group-benzamide,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-difluoro benzoyl amino)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides,
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid sec.-propyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (ethoxy carbonyl-methyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (carboxyl-methyl)-phenyl-acid amides,
5-(2-chloro-4-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-oxygen-2-(piperidines-1-yl)-ethyl]-phenyl-acid amides,
5-(5-fluoro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-methoxyl group-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-ethyl)-phenyl-acid amides,
5-(2-fluoro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-2,6-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-3-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethylamino formyl radical methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isobutyl--phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxycarbonyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-ethoxy carbonyl-propyl group)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-carboxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-propyl group)-phenyl-acid amides,
5-(2-hydroxyl-4-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-hydroxy-5-methyl oxygen base-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-hydroxyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-phenyl-acid amides,
5-(2,5-dimethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-pyridine-2-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,6-two chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl-phenyl)-acid amides,
5-(2-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-6-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-pyridine-4-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(morpholine-4-base formamyl)-benzamide dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-acetic acid sodium salt,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-propionic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(morpholine-4-base formamyl)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[2-(morpholine-4-yl)-ethylamino formyl radical]-the pyridin-4-yl methyl }-the acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-base formamyl)-pyridin-4-yl methyl]-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides 1/2 vitriol
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-amino methyl-pyridine-2-ylmethyl)-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dimethanesulfonate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(morpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-diethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-2-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 5-methyl-pyrazine-2-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-methylpiperazine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-dimethylamino-piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(tetramethyleneimine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid carbamyl ylmethyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formamyl-phenyl)-methyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(4-methylamino formyl radical-phenyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formyl-dimethylamino-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(4H-[1,2,4] triazole-3-yl)-phenyl]-amide hydrochloride,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(N-hydroxyl carbamimidoyl)-phenyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-2,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2,2-dimethyl-propionyl oxygen base)-methoxycarbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[N-(methoxyl group-thiocarbonyl oxygen base)-carbamimidoyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-sulfo--4,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-4,5-dihydro-[1,2,4] thiadiazoles-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(cyclohexyl oxygen base-ketonic oxygen base)-ethoxy carbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-thiazol-2-yl)-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-cyano group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(toluene-4-sulfuryl amino)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-6-fluoro-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-4,5-two fluoro-benzamide hydrochloride salts,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (7-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-4H-quinazoline-3-yl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-2-methyl isophthalic acid, 4-dihydro-2H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(N-hydroxyl carbamimidoyl)-pyridin-4-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(5-oxygen-4,5-dihydro-[1,2,4] diazole-3-yl)-pyridin-4-yl methyl]-acid amides,
4-{[5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,6-two chloro-5-fluoro-pyridine-3-carbonylaminos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-benzo [b] thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-benzoyl-amido-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-phenyl acetyl amino-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-amino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methylsulfonyl amino-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-acetylamino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3,4,5-three chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(1H-tetrazolium-5-yl)-pyridin-4-yl methyl]-acid amides and
1H-pyrazoles-3,5-dicarboxylic acid 3-benzamide 5-[(2,4-two chloro-phenyl)-acid amides].
56. the therapeutical agent or the preventive of an insulin resistance disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, atheroma arteriosclerosis, tissue ischemia disease, myocardial ischemia disease, obesity or bacillary, fungoid, parasitic rerum natura or viral infection disease, it is an effective constituent with admissible salt on the pyrazole compound of any one record among the above-mentioned 36-55 or its pharmacology.
57. a medicine, it is by therapeutical agent or the preventive and the formation of other drug regimen of record in will above-mentioned 56.
The invention effect
Pyrazole compound of the present invention is compared with remedy for diabetes in the past, activity is stronger, be free from side effects, the liver glycogen phosphorylase restraining effect that has oral absorption and metabolic stability excellence simultaneously, not only very useful as new treatment of diabetes or prophylactic compositions, but also be expected to as the insulin resistance disease, diabetic neuropathy, diabetic nephropathy, the diabetic retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, the atheroma arteriosclerosis, tissue ischemia disease, the therapeutical agent of myocardial ischemia disease; Appetite stimulator therapeutical agent and at the therapeutical agent of obesity; The infection Remedies of bacillary, fungoid, parasitic rerum natura or viral infection disease etc. uses.
Embodiment
The pyrazoles skeleton of pyrazole compound of the present invention not only refers to following structures,
But also comprise isomer as described below.
Therefore, pyrazole compound of the present invention is not limited to the pyrazole compound of above-mentioned general formula (I) expression, also comprises pyrazole compound as described below (I ').
Each substituting group and each position of using in this specification sheets in addition, are defined as follows.
So-called " halogen atom " is fluorine, chlorine, bromine or iodine atom.Preferred fluorine atom or chlorine atom.
So-called " C
1-6Alkyl " be meant that carbon number is 1 to 6 a straight chain shape or a catenate alkyl; for example; methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, isopentyl, 2-methyl butyl, neo-pentyl, 1-ethyl propyl, hexyl, isohexyl, 4-methyl amyl, 3-methyl amyl, 2-methyl amyl, 1-methyl amyl, 3; 3-dimethylbutyl, 2; 2-dimethylbutyl, 1; 1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 1-ethyl-butyl, 2-ethyl-butyl.Preferred C
1-4Alkyl.
So-called " C
1-4Alkyl " be meant that carbon number is 1 to 4 a straight chain shape or a catenate alkyl, for example, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl.Preferable methyl.
So-called " C
2-6Thiazolinyl " be meant the carbon number with at least more than one pair key be 2 to 6 also can the ramose thiazolinyl; for example; vinyl, 1-propenyl, 2-propenyl, 1-butylene base, crotyl, 3-butenyl, 2-methyl isophthalic acid-propenyl, 1-pentenyl, pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-2-butene base, 1-hexenyl, 3-hexenyl, 2,4-hexadienyl, 5-hexenyl.Carbon numbers such as preferred vinyl, 1-propenyl, 2-propenyl, 1-butylene base be 2-4 also can ramose C
2-4Thiazolinyl, more preferably vinyl, propenyl.
So-called " C
2-6Alkynyl " be meant the carbon number with at least more than one ginseng key be 2 to 6 also can the ramose alkynyl; for example, ethynyl, 1-proyl, 2-propynyl, ethyl acetylene base, 2-butyne base, 3-butynyl, 1-pentynyl, valerylene base, 3-pentynyl, 4-pentynyl, 1-hexin base, 2-hexin base, 3-hexin base, 4-hexin base, 5-hexin base.Preferred carbon number be 2-4 also can the ramose ethynyl, C such as 1-proyl, 2-propynyl, ethyl acetylene base, 2-butyne base
2-4Alkynyl.
So-called " C
1-6Alkylidene group " be meant carbon number be 1 to 6 also can the ramose alkylidene group; for example; methylene radical, ethylidene, propylidene, butylidene, pentylidene, hexylidene etc., carbon numbers such as preferred methylene radical, ethylidene, propylidene, butylidene be 1-4 also can the ramose alkylidene group.
So-called " halo C
1-6Alkyl " be meant by more than one, preferred 1-6, preferred especially 1-3 the above-mentioned " C that above-mentioned " halogen atom " replaces
1-6Alkyl "; for example; trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, two brooethyls, fluoro methyl, 2; 2; 2-trifluoroethyl, 2,2,2-three chloroethyls, 2-bromotrifluoromethane, 2-chloroethyl, 2-fluoro ethyl, 2-iodine ethyl, 3-chloropropyl, 4-fluorine butyl, 6-iodine hexyl, 2; 2-two bromotrifluoromethanes, preferred carbon number 1-4 halo C
1-4Alkyl.
So-called " C
1-6Alkoxyl group " be meant its alkyl position be described definition can ramose " C
1-6Alkyl " carbon number be 1 to 6 alkoxyl group; for example; methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert.-butoxy, pentyloxy, isopentyloxy, 2-methyl butoxy, 1-ethyl propoxy-, 2-ethyl propoxy-, neopentyl oxygen, hexyloxy, 4-methyl pentyloxy, 3-methyl pentyloxy, 2-methyl pentyloxy, 3; 3-dimethyl butoxy, 2; 2-dimethyl butoxy, 1; 1-dimethyl butoxy, 1,2-dimethyl butoxy, 1,3-dimethyl butoxy, 2,3-dimethyl butoxy.Carbon numbers such as preferred methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy are 1 to 4 C
1-4Alkoxyl group.
So-called " by C
1-6The C that alkoxyl group replaces
1-6Alkyl " or " C
1-6Alkoxy C
1-6Alkyl " be meant by above-mentioned can ramose " C
1-6Alkoxyl group " the above-mentioned of replacement can ramose " C
1-6Alkyl "; for example, methoxymethyl; ethoxyl methyl; propoxy-methyl; isopropoxy methyl; butoxymethyl, the isobutoxy methyl, the sec-butoxy methyl, the tert.-butoxy methyl, the 2-methoxy ethyl, the 2-ethoxyethyl group, 2-propoxy-ethyl, 2-isopropoxy ethyl, the 2-butoxyethyl group, 2-isobutoxy ethyl, 2-sec-butoxy ethyl, 2-tert.-butoxy ethyl, the 1-methoxy ethyl, the 1-ethoxyethyl group, 1-propoxy-ethyl, 1-isopropoxy ethyl, the 1-butoxyethyl group, 1-isobutoxy ethyl, 1-sec-butoxy ethyl, 1-tert.-butoxy ethyl, the 3-isopropoxide propyl.Alkoxyl groups such as preferred methoxymethyl, ethoxyl methyl, 1-methoxy ethyl, 2-methoxy ethyl, 2-butoxyethyl group part and moieties carbon number are 1-4 C
1-4Alkoxy C
1-4Alkyl.
So-called " C
1-6Alkoxy carbonyl " be meant carbon number 1-6 above-mentioned definition can the ramose alkoxyl group combine the group that forms with carbonyl; for example; methoxycarbonyl; ethoxy carbonyl; propoxycarbonyl; isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl, the sec-butoxy carbonyl, tert-butoxycarbonyl, pentyloxy carbonyl, the isopentyloxy carbonyl, 2-methyl butoxy carbonyl, the neopentyl oxygen carbonyl, 1-ethyl propoxycarbonyl, hexyloxy carbonyl, 4-methyl pentyloxy carbonyl, 3-methyl pentyloxy carbonyl, 2-methyl pentyloxy carbonyl, 1-methyl pentyloxy carbonyl, 3,3-dimethyl butoxy carbonyl, 2,2-dimethyl butoxy carbonyl, 1,1-dimethyl butoxy carbonyl, 1,2-dimethyl butoxy carbonyl, 1,3-dimethyl butoxy carbonyl, 2,3-dimethyl butoxy carbonyl, 2-ethyl butoxy carbonyl etc.Alkoxyl group part carbon numbers such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl are the (C of 1-4
1-4Alkoxyl group) carbonyl.
So-called " C
1-6Alkoxy-carbonyl oxy " be meant above-mentioned definition can ramose " C
1-6Alkoxy carbonyl " combine the group that forms with Sauerstoffatom; for example; methoxycarbonyl oxygen base; ethoxy carbonyl oxygen base; propoxycarbonyl oxygen base; isopropoxy carbonyl oxygen base, butoxy carbonyl oxygen base, isobutoxy carbonyl oxygen base, sec-butoxy ketonic oxygen base, tert-butoxycarbonyl oxygen base, pentyloxy carbonyl oxygen base, isopentyloxy ketonic oxygen base, 2-methyl butoxy carbonyl oxygen base, neopentyl oxygen ketonic oxygen base, 1-ethyl propoxycarbonyl oxygen base, hexyloxy carbonyl oxygen base, 4-methyl pentyloxy ketonic oxygen base, 3-methyl pentyloxy ketonic oxygen base, 2-methyl pentyloxy ketonic oxygen base, 1-methyl pentyloxy ketonic oxygen base, 3,3-dimethyl butoxy ketonic oxygen base, 2,2-dimethyl butoxy ketonic oxygen base, 1,1-dimethyl butoxy ketonic oxygen base, 1,2-dimethyl butoxy ketonic oxygen base, 1,3-dimethyl butoxy ketonic oxygen base, 2,3-dimethyl butoxy ketonic oxygen base or 2-ethyl butoxy carbonyl oxygen base etc.Alkoxyl group part carbon numbers such as preferred methoxycarbonyl oxygen base, ethoxy carbonyl oxygen base, propoxycarbonyl oxygen base, isopropoxy carbonyl oxygen base, butoxy carbonyl oxygen base are the (C of 1-4
1-4Alkoxyl group) ketonic oxygen base.
So-called " C
1-6The alkyl-carbonyl oxygen base " being meant can the above-mentioned " C of ramose
1-6Alkyl " combine the alkyl-carbonyl oxygen base that forms with the ketonic oxygen base, for example, can enumerate acetoxyl group, propionyloxy, butyryl acyloxy, isobutyl acyloxy, penta acyloxy, isoamyl acyloxy, pivaloyl oxygen base, hexylyloxy etc.
So-called " C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl " by above-mentioned " C
1-6The alkyl-carbonyl oxygen base " " the C that replaces
1-6Alkyl ", preferably by C
1-4The C that the alkyl-carbonyl oxygen base replaces
1-4Alkyl.
What is called " can be by C
1-6The C that alkoxy carbonyl replaces
1-6Alkoxyl group " be meant unsubstituted C
1-6Alkoxyl group or by C
1-6The C that alkoxy carbonyl replaces
1-6Alkoxyl group, so-called by C
1-6The C that alkoxy carbonyl replaces
1-6Alkoxyl group refers to by " the C of above-mentioned definition
1-6Alkoxy carbonyl " " the C that replaces
1-6Alkoxyl group ".Preferred unsubstituted C
1-4Alkoxyl group or by C
1-4The C that alkoxy carbonyl replaces
1-4Alkoxyl group.
So-called " methylene radical dioxy base ", " ethylidene dioxy base " refer to respectively-O-CH
2-O-,-O-C
2H
4-O-.
What so-called " acyl group " was meant that saturated or undersaturated alkyl combines formation with carbonyl can ramose C
2-7Aliphatic acyl radical or aromatic acyl.As aliphatic acyl radical, can enumerate for example ethanoyl, propionyl, butyryl radicals, isobutyryl, pentanoyl, isovaleryl, pivaloyl group, caproyl, acryl, methacryloyl, crotonoyl etc.In addition, as aromatic acyl, can enumerate the halogenated aryl carbonyl, 2,4 of the aryl carbonyl, 2-benzoyl bromide, 4-chlorobenzene formacyl and so on of benzoyl, α-naphthoyl base, β-naphthoyl base and so on, the C of 6-trimethylbenzoyl, 4-toluyl and so on
1-6The C of alkylated aryl carbonyl, 4-methoxybenzoyl base and so on
1-6The C of the nitration aryl carbonyl of alkoxylate aryl carbonyl, 4-nitro benzoyl, 2-nitro benzoyl and so on, 2-(methoxycarbonyl) benzoyl and so on
1-6The arylation aryl carbonyl of alkoxy carbonyl aryl carbonyl, 4-phenyl benzoyl and so on etc.
So-called " C
1-6Alkylamino " be meant following " single C
1-6Alkylamino " or " two C
1-6Alkylamino ".Preferred carbon number is the " C of 1-4
1-4Alkylamino ".
So-called " single C
1-6Alkylamino " be meant by 1 " C of above-mentioned definition
1-6Alkyl " amino that replaces; for example; methylamino; ethylamino; propyl group amino; sec.-propyl amino, butyl amino, isobutylamino, sec-butyl amino, tertiary butyl amino, amyl group amino, isopentyl amino, 2-methyl butyl amino, neo-pentyl amino, 1-ethyl propyl amino, hexyl amino, isohexyl amino, 4-methyl amyl amino, 3-methyl amyl amino, 2-methyl amyl amino, 1-methyl amyl amino, 3,3-dimethylbutyl amino, 2,2-dimethylbutyl amino, 1,1-dimethylbutyl amino, 1,2-dimethylbutyl amino, 1,3-dimethylbutyl amino, 2, list-C such as 3-dimethylbutyl amino or 2-ethyl-butyl amino
1-6Alkylamino.Preferable methyl amino, ethylamino, propyl group amino, sec.-propyl amino, butyl amino, isobutylamino etc. are by 1 C
1-4List-C that alkyl replaces
1-4Alkylamino.
So-called " two C
1-6Alkylamino " be meant by two identical or different " C of above-mentioned definition
1-6Alkyl " amino that replaces, for example two C of dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropyl amino, dibutylamino, diamyl amino or dihexyl amino and so on
1-6Alkylamino.Preferred dimethylamino, diethylamino etc. are by 2 C
1-4Two C that alkyl replaces
1-4Alkylamino.
So-called " amido " is meant the amino that is replaced by above-mentioned " acyl group ", for example the carbon number of acetylamino, propionyl amino, butyryl radicals amino, isobutyryl amino, pentanoyl amino, isovaleryl amino, pivaloyl amino, caproyl amino, acryl amino, methacryloyl amino, crotonoyl amino and so on be 2 to 7 can ramose lower aliphatic amido or the aromatic series amido of benzoyl-amido and so on.
So-called " C
1-6Alkoxycarbonyl amino " be meant by " the C of above-mentioned definition
1-6Alkoxy carbonyl " amino that replaces, for example, methoxycarbonyl amino, ethoxy carbonyl amino, propoxycarbonyl amino, isopropoxy carbonyl amino etc.(C such as preferred methoxycarbonyl amino, ethoxy carbonyl amino, propoxycarbonyl amino
1-4Alkoxyl group) carbonylamino.
So-called " formamyl " narrow sense ground refers to-CONH
2, broadly refer to-CONH
2, " list-C
1-6Alkyl-carbamoyl ", " two-C
1-6Alkyl-carbamoyl ", " ammonia diaryl base formyl radical " or " N-C
1-6Alkyl-N-aryl-amino-carbonyl ".
So-called " list-C
1-6Alkyl-carbamoyl " be meant 1 above-mentioned " C
1-6Alkyl " combine the group that forms with formamyl; for example, list-C such as methylamino formyl radical, ethylamino formyl radical, propyl group formamyl, sec.-propyl formamyl, butyl formamyl, isobutylamino formyl radical, sec-butyl formamyl, tertiary butyl formamyl, amyl group formamyl, isopentyl formamyl, 2-methyl butyl formamyl, neo-pentyl formamyl, 1-ethyl propyl formamyl, hexyl formamyl
1-6Alkyl-carbamoyl, alkyl such as preferable methyl formamyl, ethylamino formyl radical, propyl group formamyl, sec.-propyl formamyl, butyl formamyl are the list-C of the alkyl of carbon number 1-4
1-4Alkyl-carbamoyl.
So-called " two-C
1-6Alkyl-carbamoyl " be meant two identical or different above-mentioned " C
1-6Alkyl " combine the group that forms, for example two C such as formyl-dimethylamino, diethylamino formyl radical, N-ethyl-N-methylamino formyl radical, dipropyl formamyl, dibutylamino formyl radical, diamyl formamyl, dihexyl formamyl with formamyl
1-6Alkyl-carbamoyl.Alkyl such as preferred formyl-dimethylamino, diethylamino formyl radical are two-C of the alkyl of carbon number 1-4
1-4Alkyl-carbamoyl.
So-called " N-C
1-6Alkyl-N-aryl-amino-carbonyl " be meant on the nitrogen-atoms of formamyl in conjunction with " aryl " and above-mentioned " C
1-6Alkyl " group that forms; for example; N-methyl-N-phenyl amino formyl radical; N-ethyl-N-phenyl amino formyl radical; N-phenyl-N-propyl group formamyl; N-sec.-propyl-N-phenyl amino formyl radical; N-butyl-N-phenyl amino formyl radical; N-amyl group-N-phenyl amino formyl radical; N-hexyl-N-phenyl amino formyl radical; N-methyl-N-naphthyl formamyl; N-ethyl-N-naphthyl formamyl; N-naphthyl-N-propyl group formamyl; N-sec.-propyl-N-naphthyl formamyl; N-butyl-N-naphthyl formamyl; N-naphthyl-N-amyl group formamyl; N-hexyl-N-naphthyl formamyl, preferred N-methyl-N-phenyl amino formyl radical; N-ethyl-moieties such as N-phenyl amino formyl radical are that alkyl and the aryl of carbon number 1-4 is the N-C of phenyl
1-4Alkyl-N-phenyl amino formyl radical.
So-called " C
1-6Alkyl sulphonyl " be meant described " C
1-6Alkyl " combine the group that forms with alkylsulfonyl; methyl sulphonyl for example; ethylsulfonyl; sulfonyl propyl base; sec.-propyl alkylsulfonyl; butyl alkylsulfonyl; the isobutyl-alkylsulfonyl; the sec-butyl alkylsulfonyl; tertiary butyl alkylsulfonyl; the amyl group alkylsulfonyl; the isopentyl alkylsulfonyl; 2-methyl butyl alkylsulfonyl; the neo-pentyl alkylsulfonyl; 1-ethyl propyl alkylsulfonyl; the hexyl alkylsulfonyl; the isohexyl alkylsulfonyl; 4-methyl amyl alkylsulfonyl; 3-methyl amyl alkylsulfonyl; 2-methyl amyl alkylsulfonyl; 1-methyl amyl alkylsulfonyl; 3; 3-dimethylbutyl alkylsulfonyl; 2; 2-dimethylbutyl alkylsulfonyl; 1; 1-dimethylbutyl alkylsulfonyl; 1; 2-dimethylbutyl alkylsulfonyl; 1; 3-dimethylbutyl alkylsulfonyl; 2, C such as 3-dimethylbutyl alkylsulfonyl or 2-ethyl-butyl alkylsulfonyl
1-6Alkyl sulphonyl.Moieties such as preferable methyl alkylsulfonyl, ethylsulfonyl, sulfonyl propyl base, sec.-propyl alkylsulfonyl, butyl alkylsulfonyl are the C of the alkyl of carbon number 1-4
1-4Alkyl sulphonyl.More preferably methyl sulphonyl.
So-called " C
1-6Alkyl sulfonyl-amino " be meant described " C
1-6Alkyl sulphonyl " with the amino group that combine formation; methyl sulphonyl amino for example; ethylsulfonyl amino; sulfonyl propyl base amino; sec.-propyl sulfuryl amino; butyl sulfuryl amino; the isobutyl-sulfuryl amino; the sec-butyl sulfuryl amino; tertiary butyl sulfuryl amino; the amyl group sulfuryl amino; the isopentyl sulfuryl amino; 2-methyl butyl sulfuryl amino; the neo-pentyl sulfuryl amino; 1-ethyl propyl sulfuryl amino; the hexyl sulfuryl amino; the isohexyl sulfuryl amino; 4-methyl amyl sulfuryl amino; 3-methyl amyl sulfuryl amino; 2-methyl amyl sulfuryl amino; 1-methyl amyl sulfuryl amino; 3; 3-dimethylbutyl sulfuryl amino; 2; 2-dimethylbutyl sulfuryl amino; 1; 1-dimethylbutyl sulfuryl amino; 1; 2-dimethylbutyl sulfuryl amino; 1; 3-dimethylbutyl sulfuryl amino; 2, C such as 3-dimethylbutyl sulfuryl amino or 2-ethyl-butyl sulfuryl amino
1-6Alkyl sulfonyl-amino.Moieties such as preferable methyl sulfuryl amino, ethylsulfonyl amino, sulfonyl propyl base amino, sec.-propyl sulfuryl amino, butyl sulfuryl amino are the C of the alkyl of carbon number 1-4
1-4Alkyl sulfonyl-amino.
So-called " C
3-8Cycloalkyl " be meant that carbon number is 3 to 8, the individual saturated cyclic alkyls of preferred 3-6, also can be the C that in ring, contains 1 or 2 two key
3-8Cycloalkenyl group.As " saturated C
3-8Cycloalkyl " example, can enumerate cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group.In addition, " C here
3-8Cycloalkenyl group " refer to that carbon number is 3 to 8 s', preferred 5-7 a cycloalkenyl group, be in ring, contain at least one, the cycloalkenyl group of preferred 1 or 2 two key.Specifically, be cyclopropenyl radical, cyclobutene base, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 2,4-cyclohexadiene-1-base, 2,5-cyclohexadiene-1-base, cycloheptenyl, cyclooctene base etc.
So-called " C
3-8Cycloalkyl C
1-6Alkyl " be meant by described " C
3-8Cycloalkyl " above-mentioned " C that replaced
1-6Alkyl ", for example cyclopropyl methyl, cyclopropyl ethyl, cyclopentyl-methyl, cyclopentyl ethyl, cyclohexyl methyl, cyclohexyl ethyl.Moieties such as preferred cyclopropyl methyl, cyclopropyl ethyl, cyclopentyl-methyl, cyclopentyl ethyl, cyclohexyl methyl are the " C of carbon number 1-4 alkyl
3-8Cycloalkyl C
1-4Alkyl ".
So-called " C
3-8Cycloalkyl oxy " be meant " C of above-mentioned definition
3-8Cycloalkyl " combine the base that forms with Sauerstoffatom, for example, ring propoxy-, cyclobutoxy group, cyclopentyloxy, cyclohexyloxy, ring oxygen in heptan base, ring octyloxy.Cycloalkyl moieties such as preferred ring propoxy-, cyclobutoxy group, cyclopentyloxy, cyclohexyloxy are the C of the cycloalkyl of carbon number 3-6
3-6Cycloalkyl oxy.
So-called " C
3-8Cycloalkyl oxy ketonic oxygen base " be meant " C of above-mentioned definition
3-8Cycloalkyl oxy " combine the base that forms with the ketonic oxygen base, for example, ring propoxycarbonyl oxygen base, cyclobutoxy group ketonic oxygen base, cyclopentyloxy ketonic oxygen base, cyclohexyloxy carbonyl oxygen base, ring oxygen base ketonic oxygen base in heptan, ring carbonyl octyloxy oxygen base.Cycloalkyl moieties such as preferred ring propoxycarbonyl oxygen base, cyclobutoxy group ketonic oxygen base, cyclopentyloxy ketonic oxygen base, cyclohexyloxy carbonyl oxygen base are the C of the cycloalkyl of carbon number 3-6
3-6Cycloalkyl oxy ketonic oxygen base.
So-called " C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl " be meant by above-mentioned " C
3-8Cycloalkyl oxy ketonic oxygen base " " the C that replaced
1-6Alkyl ", preferred cycloalkyl moiety is the C of the cycloalkyl of carbon number 3-6
3-6Cycloalkyl oxy ketonic oxygen base and moieties are " C
1-4Alkyl " cycloalkyl oxy ketonic oxygen base alkyl.
So-called " aryl " is meant the aromatic hydrocarbyl of carbon number 6-14, for example, and phenyl, naphthyl, anthryl, indenyl, Azulene base, fluorenyl, phenanthryl etc.This aryl also can be fractional saturation sometimes.As the aryl of fractional saturation, can enumerate for example dihydro indenyl, tetralyl etc.Preferred C
6-10Aryl, more preferably phenyl or naphthyl, most preferably phenyl.
As " Q " in the formula (I) preferred phenyl.
So-called " aralkyl " can be 1 or 2 and above-mentioned " C of the aryl of carbon number 6-14
1-6Alkyl " in conjunction with the group that forms; for example benzyl, naphthyl methyl, indenyl methyl, phenanthryl methyl, anthryl methyl, diphenyl methyl, styroyl, naphthyl ethyl, phenyl propyl, naphthyl propyl group, phenyl butyl, naphthyl butyl, phenylpentyl, naphthyl amyl group or phenyl hexyl, aryl such as preferred benzyl, naphthyl methyl, diphenyl methyl or styroyl are that phenyl and alkyl are C
1-4The aralkyl of alkyl, more preferably benzyl or styroyl, especially preferably benzyl.
So-called " aryloxy " goes up the group that forms in conjunction with Sauerstoffatom in above-mentioned definition " aryl ", for example, and phenoxy group, naphthyloxy etc.Preferred phenoxy group.
So-called " aryl sulfonyl " expression above-mentioned " aryl " combines the base that forms with alkylsulfonyl, for example, and C such as phenyl sulfonyl, indenyl alkylsulfonyl, naphthyl alkylsulfonyl, phenanthryl alkylsulfonyl, anthryl alkylsulfonyl, fluorenyl alkylsulfonyl
6-14Aryl sulfonyl, preferred C
6-10Aryl combines the C that forms with alkylsulfonyl
6-10Aryl sulfonyl, more preferably phenyl sulfonyl or naphthyl alkylsulfonyl, most preferably phenyl sulfonyl.
What is called " can be by C
1-6The aryl sulfonyl that alkyl replaces " refer to above-mentioned " aryl sulfonyl " aryl by more than 1, preferred 1-3 above-mentioned " C
1-6Alkyl ", preferred " C
1-4Alkyl " group that replaces, for example, p-toluenesulfonyl.
So-called " arlysulfonylamino " refers to above-mentioned " aryl sulfonyl " and the amino base that forms that combines; for example, C such as phenyl sulfonyl amino, indenyl sulfuryl amino, naphthyl sulfuryl amino, phenanthryl sulfuryl amino, anthryl sulfuryl amino, fluorenyl sulfuryl amino
6-14Arlysulfonylamino, preferred C
6-10Arlysulfonylamino, more preferably phenyl sulfonyl amino or naphthyl sulfuryl amino, most preferably phenyl sulfonyl amino.
So-called " phenyl that can be replaced by halogen atom " refers to by phenyl more than 1, that preferred 1-3 the identical or different halogen atom that is selected from fluorine atom, chlorine atom, bromine atoms and iodine atom has replaced.
What is called " can be by halo C
1-6The phenyl that alkyl replaces " refer to by above-mentioned " halo C identical or different more than 1
1-6Alkyl " phenyl that replaces.
So-called " heterocyclic radical " is meant, as the atom that constitutes ring, except carbon atom, has 1 to 4 the identical or different heteroatoms that is selected from Sauerstoffatom, nitrogen-atoms or the sulphur atom, the number that constitutes the atom of ring is 3-14, the individual unsaturated ring of saturated rings, part, the aromatic series cyclic group of preferred 5-7, the ring that constitutes them both can be a monocycle, also can be condensed ring.
So-called " monocyclic saturated heterocyclyl " refers to heterocyclic radical saturated or can fractional saturation, for example, pyrrolidyl, tetrahydrofuran base, tetrahydro-thienyl, imidazolidyl, pyrazolidyl, 1,3-dioxolanyl, 1,3-oxygen thia penta ring (oxathiolane) Ji, oxazolidinyl, thiazolidyl, piperidyl, piperazinyl, THP trtrahydropyranyl, tetrahydro thiapyran base, two alkyl, morpholinyl, thio-morpholinyl, 2-oxo-pyrrolidine base, 2-oxo-piperidine base, 4-oxo-piperidine base, 2,6-dioxopiperidine base etc.Five yuan of preferred pyrrolidyl, piperidyl and morpholinyls etc. are to the hexavalent saturated heterocyclyl.
So-called " five yuan or the monocyclic saturated heterocyclyl of hexavalent " is meant five yuan or hexavalent heterocyclic radical among above-mentioned " monocyclic saturated heterocyclyl ".Constitute the heterocycle of such heterocyclic radical, promptly " five yuan or the monocyclic saturated heterocyclic of hexavalent " is tetrahydrofuran (THF), 1 for example, five-membered ring, tetrahydropyranss, 1 such as 3-dioxolane, tetramethylene sulfide, tetramethyleneimine, pyrazolidine, imidazolidine, 4-two alkane, thiane, 1, hexavalent heterocycles such as 4-two thiane, piperidines, piperazine, morpholine.This heterocyclic radical also can partly have two keys.
So-called " contain 1-4 and be selected from sulphur atom; the heteroatomic quinary heterocyclic radical of Sauerstoffatom and nitrogen-atoms " is furyl for example, thienyl, pyrryl, pyrazolyl, imidazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, the di azoly, triazolyl, tetrazyl, 5-membered aromatic family heterocyclic radicals such as thiadiazolyl group, example as the monocyclic heterocycles base of saturated or fractional saturation, can enumerate tetrahydrofuran (THF)-2-base, tetrahydrofuran (THF)-3-base, imidazolidine-1-base, imidazolidine-2-base, imidazolidine-4-base, tetramethyleneimine-1-base, tetramethyleneimine-2-base, tetramethyleneimine-3-base, 1,3- azoles alkane-3-base, isothiazolidine-2-base, 1,3-thiazolidine-3-base, 1,2-pyrazolidine-2-base, 1,2-pyrazolidine-1-base etc.
So-called " five yuan or the monocyclic saturated heterocyclyl of hexavalent with at least one nitrogen-atoms " is meant to have at least one nitrogen-atoms, can also have 1-3 heteroatomic five yuan or the monocyclic saturated heterocyclyl of hexavalent being selected from nitrogen-atoms, sulphur atom and Sauerstoffatom in addition.The heterocycle that constitutes five yuan heterocyclic radical is for example tetramethyleneimine, pyrazolidine, imidazolidine, azoles alkane, thiazolidine etc., and the heterocycle that constitutes the hexavalent heterocyclic radical is for example piperidines, piperazine, morpholine, diazine etc.Saturated heterocyclic also can partly have two keys.
So-called " monocyclic aromatic heterocycle " is for example pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, 1,3,5-triazinyl, pyrryl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl group etc.Be preferably five yuan or hexavalent aromatic heterocycle.
" saturated heterocyclic " in so-called " can form saturated heterocyclic with adjacent nitrogen-atoms " refers to, for example, as the atom that constitutes ring, except carbon atom, also contain at least one nitrogen-atoms, and can contain 1-2 be selected from Sauerstoffatom, sulphur atom and nitrogen-atoms heteroatomic five yuan to the heptatomic nitrogen heterocyclic ring, for example tetramethyleneimine, imidazolidine, pyrazolidine, piperidines, piperazine, morpholine, thiomorpholine etc.
So-called " saturated heterocyclyl can form condensed ring with the phenyl ring condensation " is meant, for example, above-mentioned " monocyclic saturated heterocyclyl " can form condensed ring with the phenyl ring condensation, for example indolinyl, iso-dihydro-indole-group, 2,3-dihydro benzo furyl, benzothiazolyl, chromanyl (chromanyl).
So-called " aromatic heterocycle " refers to, as the atom that constitutes ring, except carbon atom, have 1 to 4 the identical or different heteroatoms that is selected from Sauerstoffatom, nitrogen-atoms or the sulphur atom, the number that constitutes the atom of ring is 3-14, preferred 5-7, more preferably 5-6 aromatic series cyclic group or its condensed ring radical.These aromatic heterocycles can be replaced by oxygen base more than 1 or sulfenyl.So-called aromatic heterocycles that these are replaced by oxygen base or sulfenyl are meant the aromatic heterocycle that replaced by hydroxyl or thiol group and as their heterocyclic radical with oxygen base or sulfenyl of keto-enol tautomerism body.Example as aromatic heterocycle, be not limited to following group, can enumerate pyridyl, pyridazinyl, imidazolyl, pyrimidyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl (quinolyl), isoquinolyl, tetrazyl, furyl, thienyl, different azoles base, thiazolyl, azoles base, isothiazolyl, pyrryl, quinolyl (quinolinyl), isoquinolyl, indyl, benzimidazolyl-, benzofuryl, cinnolinyl, indazolyl, indolizine base (indolizinyl), phthalazinyl, pyridazinyl, triazinyl, pseudoindoyl, purine radicals (purinyl), the di azoly, thiazolyl, thiadiazolyl group, the furazan base, benzo furazan base, benzothienyl, the benzotriazole base, benzothiazolyl, the benzoxazol base, quinazolyl, quinoline quinoline base, naphthyridinyl (naphthylizinyl), the dihydroquinoline base, furopyridinyl, pyrrolo-pyrimidine radicals, and azaindolyl.
So-called " five yuan or hexavalent aromatic heterocycle " refers to, as the atom that constitutes ring, except carbon atom, have 1 to 4 the identical or different heteroatoms that is selected from Sauerstoffatom, nitrogen-atoms or the sulphur atom, the number that constitutes the atom of ring is 5-6 aromatic series cyclic group or its condensed ring radical.For example, pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, 1,2, the 4-triazolyl, 1,2, the 3-triazolyl, tetrazyl, 1,3,4- di azoly, 1,2,4- di azoly, 1,3, the 4-thiadiazolyl group, 1,2, the 4-thiadiazolyl group, the furazan base, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, 1,3, the 5-triazinyl, imidazolinyl, pyrazolinyl, azoles quinoline base (2- azoles quinoline base, 3- azoles quinoline base, 4- azoles quinoline base), different azoles quinoline base, thiazolinyl, the isothiazoline base, pyranyl, 2-oxo pyranyl, 2-oxygen-2,5-dihydrofuran base.Preferred pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, pyridyl, 2-oxygen-2,5-dihydrofuran base.
So-called " five yuan or the hexavalent aromatic heterocycle that can be replaced by oxygen base or sulfenyl " be meant above-mentioned five yuan or hexavalent aromatic heterocycle can by the identical or different oxygen base more than 1 (=O) or the sulfenyl (=aromatic heterocycle that S) replaces.So-called these five yuan of being replaced by oxygen base or sulfenyl or hexavalent aromatic heterocycle are meant five yuan of being replaced by hydroxyl or thiol group or hexavalent aromatic heterocycle and as their heterocyclic radical with oxygen base or sulfenyl of keto-enol tautomerism body.
What is called " can be by carboxyl or C
1-6Five yuan or hexavalent aromatic heterocycle that alkoxy carbonyl replaces " being meant can be by carboxyl more than 1 or above-mentioned " C
1-6Alkoxy carbonyl " above-mentioned " five yuan or the hexavalent aromatic heterocycle " that replace.
So-called " aromatic heterocycle both can be that monocycle also can be a condensed ring " is meant that mix carbocylic radical or other heterocyclic radical of monocyclic aromatic heterocycle or monocyclic aromatic heterocycle and the aromatic series such as phenyl ring more than 1 condenses the group of formation.
So-called " monocyclic aromatic heterocycle or condense the aromatic heterocycle of formation with phenyl ring " refers to for example thienyl, furyl, pyrryl, imidazolyl, pyrazolyl, isothiazolyl, different azoles base, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, " monocyclic aromatic heterocycles " such as azoles bases, perhaps benzofuryl, isobenzofuran-base, benzo [b] thienyl, indyl, pseudoindoyl, the 1H-indazolyl, benzimidazolyl-benzoxazolyl, benzothiazolyl, 1H-benzotriazole base, quinolyl, isoquinolyl, cinnolinyl, quinazolyl, quinoxalinyl, phthalazinyl etc. and phenyl ring condense the aromatic heterocycle of formation.
So-called " condense the C that the aromatic heterocycle of formation replaces by monocyclic aromatic heterocycle or with phenyl ring
1-6Alkyl " refer to " C that replaced by " the monocyclic aromatic heterocycle or condense the aromatic heterocycle of formation with phenyl ring " of above-mentioned definition
1-6Alkyl ".Preferably by the " C of " monocyclic aromatic heterocycle " replacement
1-6Alkyl ".
As " condensed heterocycle base ", can enumerate indyl (for example, 4-indyl, 7-indyl etc.), pseudoindoyl, 1,3-dihydro-1,3-dioxy pseudoindoyl, benzofuryl (for example, 4-benzofuryl, 7-benzofuryl etc.), indazolyl, isobenzofuran-base, benzothienyl (for example, 4-benzothienyl, 7-benzothienyl etc.), benzoxazol base (4-benzoxazol base, 7-benzoxazol base etc.), benzimidazolyl-(for example, 4-benzimidazolyl-, 7-benzimidazolyl-etc.), benzothiazolyl (for example, 4-benzothiazolyl, 7-benzothiazolyl etc.), indolizine base, quinolyl, isoquinolyl, 1,2-dihydro-2-oxoquinoline base, quinazolyl, quinoline quinoline base, cinnolinyl, phthalazinyl, quinolizinyl, purine radicals, pteridyl, indolinyl, iso-dihydro-indole-group, 5,6,7,8-tetrahydric quinoline group, 1,2,3,4-tetrahydric quinoline group, 2-oxo-1,2,3,4-tetrahydric quinoline group, benzo [1,3] dioxolyl (dioxolyl), 3,4-methylene radical dioxo pyridyl, 4,5-ethylene oxo-pyrimidine base, chromenyl, chromanyl, different chromanyl etc.
So-called " can be replaced by the substituting group more than 1 " is meant and can be replaced by above substituting group by identical or different 1, refer to that preferably individual by 1-6, preferred especially 1-3 identical or different substituting group replaces.In addition, even without the substituent quantity of special record, it in fact also is meant " can be replaced by the substituting group more than 1 ".So-called " identical or different " is meant that among a plurality of substituting groups, all substituting groups are identical, and the situation that perhaps all substituting groups differ from one another perhaps refers among the substituting group more than 3,2 situations that substituting group is identical.
Below, preferred base in the above-mentioned general formula (I) etc. is narrated, but compound of the present invention is not limited to this.
" aryl " among the ring Q is preferably C
6-10Aryl, more preferably phenyl or naphthyl, most preferably phenyl.
" aromatic heterocycle " among the ring Q is preferably " containing 1-4 heteroatomic five yuan or hexavalent aromatic heterocycle that is selected from sulphur atom, Sauerstoffatom and nitrogen-atoms ", more preferably thienyl or pyridyl.
As ring Q, be preferably phenyl or pyridyl, be preferably phenyl especially.
R
1Be preferably hydrogen atom, halogen atom, C
1-4Alkyl or C
1-4Alkoxyl group, more preferably hydrogen atom or halogen atom are preferably hydrogen atom, fluorine atom or chlorine atom especially, and more preferably hydrogen atom or fluorine atom most preferably are fluorine atom.
R
2Be preferably halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group or azido-, more preferably halogen atom is preferably fluorine atom or chlorine atom, more preferably fluorine atom especially.
R
3Be preferably halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-4Alkyl, C
1-4Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino, more preferably halogen atom or C
1-4Alkyl is preferably fluorine atom, chlorine atom or methyl especially, more preferably chlorine atom or methyl.
Substituting group (R as ring Q
1, R
2And R
3) R preferably
1For being positioned at 5 hydrogen atom, fluorine atom or chlorine atom, more preferably fluorine atom or hydrogen atom, R
2For being positioned at 4 fluorine atom or chlorine atom, more preferably fluorine atom, R
3For being positioned at 2 chlorine atom or methyl, preferred chlorine atom.
Be substituted basic R
1, R
2And R
3The ring Q that replaces is preferably base as described below,
More preferably following 2-chloro-4, the 5-difluorophenyl.
R
4Be preferably and be selected from following 1 '-7 ' base.
1 '. hydrogen atom,
2 ' .C
1-6Alkyl or be selected from the C that the substituting group of following group of A ' replaces
1-6Alkyl;
[group A ']
A ' 1. hydroxyl,
A ' 2.C
1-4Alkoxyl group (C wherein
1-4Alkoxyl group is for example methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, is preferably methoxyl group, oxyethyl group, propoxy-or isopropoxy especially.)；
A ' 3.-N (R
41) (R
41') (wherein, R
41And R
41' identical or different, preferably represent hydrogen atom, C
1-4Alkyl or R
41And R
41' with five yuan or the monocyclic saturated heterocyclic of hexavalent that adjacent nitrogen-atoms forms, preferred-N (R
41) (R
41') be amino, methylamino, ethylamino, dimethylamino, diethylamino, piperidyl, morpholino base, pyrrolidyl, piperazinyl, more preferably amino, methylamino, ethylamino, dimethylamino, diethylamino, piperidyl, morpholino base, pyrrolidyl or piperazinyl.)；
A ' is phenyl or naphthyl (preferred phenyl 4..)；
A ' is five yuan or hexavalent aromatic heterocycle (preferred pyridyl 5..)；
A ' 6.-CO-N (R
411) (R
411') (for example ,-CONH
2, list-C
1-4Alkyl-carbamoyl, two-C
1-4Alkyl-carbamoyl, N-C
1-4Alkyl N-aryl-amino-carbonyl, formyl-dimethylamino, diethylamino formyl radical, morpholino carbonyl, pyrrolidyl carbonyl, piperazinyl carbonyl, preferable methyl formamyl, ethylamino formyl radical, formyl-dimethylamino or diethylamino formyl radical.)
A ' 7. carboxyl and
A ' 8.C
1-4Alkoxy carbonyl (for example, methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl, preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl or isopropoxy carbonyl.)；
3 ' .C
2-4Thiazolinyl (for example, vinyl, 1-propenyl, 2-propenyl, 1-butylene base, crotyl, 3-butenyl, 2-methyl isophthalic acid-propenyl, preferred vinyl, 1-propenyl or 2-propenyl);
4 ' .C
2-4Alkynyl (for example, ethynyl, 1-proyl, 2-propynyl, ethyl acetylene base, preferred ethynyl, 1-proyl, 2-propynyl.)；
5 ' .C
3-6Cycloalkyl (more specifically, is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.)；
6 ' .C
3-6Cycloalkyl C
1-4Alkyl (preferred cyclopropyl methyl, cyclopropyl ethyl, cyclobutylmethyl, cyclobutyl ethyl, cyclopentyl-methyl, cyclopentyl ethyl, cyclohexyl methyl, cyclohexyl ethyl.)；
7 '. aryl (for example, phenyl, naphthyl, preferred phenyl.)；
R
5Be preferably and be selected from following 1 '-8 ' group.
1 ' .C
1-6Alkyl or be selected from the C that the substituting group of following group of B ' replaces
1-6Alkyl (more preferably C
1-6Alkyl.)；
[group B ']
B ' is hydroxyl 1.;
B ' 2.C
1-4Alkoxyl group (for example, C such as methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy
1-4Alkoxyl group.)；
B ' 3.-N (R
51) (R
51') (R
51And R
51' identical or different, preferably represent hydrogen atom, C
1-4Alkyl or R
51And R
51' saturated heterocyclic that forms with adjacent nitrogen-atoms, for example, amino, methylamino, ethylamino, dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropyl amino, piperidyl, morpholino base, pyrrolidyl, piperazinyl, more preferably amino, methylamino, ethylamino, dimethylamino, diethylamino.)
And
B ' 4.-CO-N (R
51) (R
51') (R
51And R
51' same as described above.Particularly; be methylamino formyl radical, ethylamino formyl radical, formyl-dimethylamino, diethylamino formyl radical, morpholino carbonyl, pyrrolidyl carbonyl, piperazinyl carbonyl etc., preferable methyl formamyl, ethylamino formyl radical, formyl-dimethylamino or diethylamino formyl radical.)；
2 ' .C
3-8(for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group are preferably the C that is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl to cycloalkyl
3-6Cycloalkyl.)；
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-4Alkoxy carbonyl (preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl or isopropoxy carbonyl) replaces, and in addition, also can condense with pyridine ring and forms group as described below.)
3 '. by C
3-8The C of cycloalkyl substituted
1-6Alkyl is (preferably by C
3-6The C of cycloalkyl substituted
1-4Alkyl is especially preferably by C
3-6The C of cycloalkyl substituted
1-2Alkyl.Particularly, can enumerate cyclopropyl methyl, cyclopropyl ethyl, cyclobutylmethyl, cyclobutyl ethyl, cyclopentyl-methyl, cyclopentyl ethyl, cyclohexyl methyl, cyclohexyl ethyl etc.)；
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be selected from hydroxyl, carboxyl and C
1-6Alkoxy carbonyl (C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl
1-4Alkoxy carbonyl) substituting group replaces.)
4 '. can be selected from that the more than one substituting group of following group of C ' replaces five yuan or the monocyclic saturated heterocyclyl of hexavalent are (wherein, preferred five yuan or the monocyclic saturated heterocyclyl of hexavalent are pyrrolidyls for example, tetrahydrofuran base, tetrahydro-thienyl, imidazolidyl, pyrazolidyl, 1, the 3-dioxolanyl, 1,3-oxygen thia penta cyclic group oxazolidinyl, thiazolidyl, piperidyl, piperazinyl, THP trtrahydropyranyl, tetrahydro thiapyran base, two alkyl, morpholinyl, thio-morpholinyl, 2-oxo-pyrrolidine base, 2-oxo-piperidine base, 4-oxo-piperidine base, 2,6-dioxopiperidine base, more preferably pyrrolidyl, piperidyl, morpholinyl etc.Most preferably be hexa-atomic saturated heterocyclyl as described below.)；
[group C ']
C ' 1.C
1-6Alkyl (C such as preferable methyl, ethyl, propyl group, sec.-propyl, butyl
1-4Alkyl.)；
C ' is acyl group (for example, ethanoyl, propionyl, butyryl radicals, benzoyl, preferred ethanoyl, propionyl or butyryl radicals) 2.;
C ' 3.C
1-6Alkyl sulphonyl (for example, methyl sulphonyl, ethylsulfonyl, sulfonyl propyl base, sec.-propyl alkylsulfonyl, butyl alkylsulfonyl, preferable methyl alkylsulfonyl or ethylsulfonyl.)；
C ' is carboxyl 4.;
C ' 5.C
1-6Alkoxy carbonyl (C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl
1-4Alkoxy carbonyl.)；
And
C ' 6.-CO-(Alk)
n-COOR
52, (preferred R
52Be hydrogen atom or C
1-4Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-2.)
5 '. aryl or be selected from the aryl of more than of following group of D ', preferred 1-3 substituting group replacement (wherein, aryl is for example phenyl, naphthyl, is preferably phenyl.)；
[group D ']
D ' is hydroxyl 1.;
D ' 2.C
1-6Alkoxyl group (C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl
1-4Alkoxy carbonyl.)；
D ' is cyano group 3.;
D ' 4.C
1-6Alkyl (C such as preferable methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl
1-4Alkyl.)；
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-4The more than one substituting group of alkoxy carbonyl (for example, methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl) replaces.)；
D ' 5.-N (R
53) (R
53') (R wherein
53And R
53' be preferably hydrogen atom, C
1-4Alkyl, C
1-4Alkyl sulphonyl particularly, can be enumerated amino, methylamino, ethylamino, dimethylamino, diethylamino, methyl sulphonyl amino, ethylsulfonyl amino.)；
D ' 6.-CO-N (R
53) (R
53') (R wherein
53And R
53' be preferably hydrogen atom, C
1-4Alkyl, C
1-4Alkyl sulphonyl; particularly; can enumerate formamyl, formyl-dimethylamino, diethylamino formyl radical, preferable methyl formamyl, ethylamino formyl radical, formyl-dimethylamino, diethylamino formyl radical, methyl sulphonyl formamyl.)；
D ' 7.-COOR
54(wherein, R
54Be hydrogen atom, C
1-4Alkyl (for example, methyl, ethyl, propyl group, sec.-propyl, butyl etc.), C
1-4Alkyl-carbonyl oxygen base C
1-4Alkyl (for example, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, propyl group ketonic oxygen ylmethyl etc.) or C
3-6Cycloalkyl oxy ketonic oxygen base C
1-4Alkyl (for example, cyclohexyl oxygen base ketonic oxygen ylmethyl, cyclohexyl oxygen base ketonic oxygen base ethyl etc.).Preferred especially R
54Be hydrogen atom, C
1-4Alkyl.)；
D ' 8.-C (NH (OH))=N-R
55(wherein, R
55Be preferably hydrogen atom or C
1-6Alkyl sulphonyl (for example, methyl sulphonyl etc.)。)；
9. five yuan or the monocyclic saturated heterocyclyl of hexavalent be (for example for D ', pyrrolidyl, tetrahydrofuran base, tetrahydro-thienyl, imidazolidyl, pyrazolidyl, 1, the 3-dioxolanyl, 1,3-oxygen thia penta cyclic group oxazolidinyl, thiazolidyl, piperidyl, piperazinyl, THP trtrahydropyranyl, tetrahydro thiapyran base, two alkyl, morpholinyl, thio-morpholinyl, 2-oxo-pyrrolidine base, 2-oxo-piperidine base, 4-oxo-piperidine base, 2,6-dioxopiperidine base preferably has at least-pyrrolidyl of individual nitrogen-atoms, piperidyl, five yuan of morpholinyls etc. or hexavalent saturated heterocyclyl.Hexa-atomic saturated heterocyclyl more preferably as described below.)、
And
Five yuan of 10. can be replaced by oxygen base or sulfenyl of D ' or the monocyclic aromatic heterocycle of hexavalent are (for example, pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, 1,2, the 4-triazolyl, 1,2, the 3-triazolyl, tetrazyl, 1,3,4- di azoly, 1,2,4- di azoly, 1,3, the 4-thiadiazolyl group, 1,2, the 4-thiadiazolyl group, the furazan base, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, 1,3, the 5-triazinyl, imidazolinyl, pyrazolinyl, azoles quinoline base (2- azoles quinoline base, 3- azoles quinoline base, 4- azoles quinoline base), different azoles quinoline base, thiazolinyl, the isothiazoline base, pyranyl, 2-oxo pyranyl, 2-oxygen-2,5-dihydrofuran base, preferred pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, pyridyl, 2-oxygen-2,5-dihydrofuran base, the heterocyclic radical as described below five yuan that more preferably has at least two nitrogen-atoms
Heterocyclic radical more preferably as described below five yuan.)；
Above-mentioned substituent group D ' among the 1-D ' 10, particularly preferably be the substituting group that is selected from D ' 4, D ' 6, D ' 7 and D ' 10.Unsubstituted phenyl is preferably as R
5
6 '. can be selected from carboxyl and C
1-6Five yuan of replacing of the substituting group of alkoxy carbonyl or hexavalent monocycle or condense the aromatic heterocycle (C wherein of formation with phenyl ring
1-6Alkoxy carbonyl is preferably C such as methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl
1-4Alkoxy carbonyl.Aromatic heterocycle is a pyrryl for example, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, 1,2, the 4-triazolyl, 1,2, the 3-triazolyl, tetrazyl, 1,3,4- di azoly, 1,2,4- di azoly, 1,3, the 4-thiadiazolyl group, 1,2, the 4-thiadiazolyl group, the furazan base, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, 1,3, the 5-triazinyl, imidazolinyl, pyrazolinyl, azoles quinoline base (2- azoles quinoline base, 3- azoles quinoline base, 4- azoles quinoline base), different azoles quinoline base, thiazolinyl, the isothiazoline base, pyranyl, 2-oxo pyranyl, 2-oxygen-2,5-dihydrofuran base, preferred pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, pyridyl, 2-oxygen-2,5-dihydrofuran base, preferred pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, 1,2, the 4-triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, thiazolinyl, isothiazoline base or pyranyl.)；
Particularly preferred five yuan or hexavalent aromatic heterocycle are following heterocyclic radicals.
7 ' .C
7-14Aralkyl (for example, the C that replaced by aromatic hydrocarbyl such as benzyl or styroyl
1-4Alkyl, for example, benzyl, naphthyl methyl, indenyl methyl, phenanthryl methyl, anthryl methyl, diphenyl methyl, styroyl, naphthyl ethyl, phenyl propyl, naphthyl propyl group, phenyl butyl, naphthyl butyl, preferred benzyl, naphthyl methyl, diphenyl methyl or styroyl, more preferably benzyl or styroyl.)；
(this C
7-14The moieties of aralkyl can not replace, and one or two substituting group that perhaps also can be selected from following group of E ' replaces.Preferred alkyl partly is unsubstituted.In addition, this C
7-14The aryl moiety of aralkyl also can be selected from more than 1 of following group of F ', preferred 1-3 substituting group replaces.)
[group E ']
The C that E ' 1. can be replaced by hydroxyl
1-4Alkyl (for example, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, methylol, hydroxyethyl.)；
E ' is cyano group 2.;
E ' is carboxyl 3.;
E ' 4.C
1-6Alkoxy carbonyl ((C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl, sec-butoxy carbonyl, tert-butoxycarbonyl
1-6Alkoxyl group) carbonyl.)；
And
E ' is phenyl 5..
[group F ']
F ' 1.C
1-6Alkyl (C such as preferable methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl
1-4Alkyl.)；
F ' is halogen atom, (for example, fluorine atom, chlorine atom, bromine atoms or iodine atom, preferred fluorine atom or chlorine atom 2..)；
F ' is cyano group 3.;
F ' is hydroxyl 4.;
F ' 5.C
1-6Alkoxyl group, by the C of carboxyl substituted
1-6Alkoxyl group or by C
1-6The C that alkoxy carbonyl replaces
1-6Alkoxyl group (wherein, C
1-6Alkoxyl group is preferably C such as methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy
1-4Alkoxyl group is by C
1-6The C that alkoxy carbonyl replaces
1-6Preferred C in the alkoxyl group
1-6Alkoxy carbonyl is C such as methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl
1-4Alkoxy carbonyl.)；
F ' is halo C 6.
1-6Alkyl, (for example, trifluoromethyl, fluoro methyl, 2,2,2-trifluoroethyl, the preferred equivalent C of trifluoromethyl
1-4Alkyl.)；
F ' is carboxyl 7.;
F ' 8.C
1-6Alkoxy carbonyl (C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl, sec-butoxy carbonyl
1-4Alkoxy carbonyl.)；
F ' 9.-CO-N (R
56a) (R
56a') (wherein, R
56aAnd R
56a' identical or different, be the C that five yuan of hydrogen atom, the piperidyl with at least one nitrogen-atoms, morpholino base, pyrrolidyl, piperazinyls etc. or the monocyclic saturated heterocyclyl of hexavalent or the more than one substituting group that is selected from following group of F ' replace
1-6Alkyl.Saturated heterocyclyl is preferably hexavalent saturated heterocyclyl as described below.
In addition, this C
1-6Alkyl is C such as methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl
1-4Alkyl.)；
[group F ']
F ' is amino 1.;
The 2. single C of F '
1-6Alkylamino, (for example, methylamino, ethylamino, propyl group amino, sec.-propyl amino, butyl amino, isobutylamino, sec-butyl amino, tertiary butyl amino, amyl group amino, isopentyl amino, 2-methyl butyl amino, neo-pentyl amino, 1-ethyl propyl amino, hexyl amino, isohexyl amino, 4-methyl amyl amino, 3-methyl amyl amino, 2-methyl amyl amino, 1-methyl amyl amino, 3,3-dimethylbutyl amino, 2,2-dimethylbutyl amino, 1,1-dimethylbutyl amino, 1,2-dimethylbutyl amino, 1,3-dimethylbutyl amino, 2,3-dimethylbutyl amino or 2-ethyl-butyl amino, preferred list-C
1-4Alkylamino.)；
F ' is two C 3.
1-6Alkylamino, (for example, dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropyl amino, dibutylamino, diamyl amino, dihexyl amino, preferred two C
1-4Alkylamino.)；
F ' is carboxyl 4.
F ' 5.C
1-6Alkoxy carbonyl, (C such as preferred methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, isobutoxy carbonyl
1-4Alkoxy carbonyl.)；
F ' is hydroxyl 6.;
And
F ' 7. has five yuan or the monocyclic saturated heterocyclyl of hexavalent (for example, piperidyl, morpholino base, pyrrolidyl, piperazinyl of at least one nitrogen-atoms.)。
F ' 10.-N (R
56b) (R
56b') (wherein, R
56bAnd R
56b' identical or different, be hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.This C
1-6Alkyl is preferably C such as methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl
1-4Alkyl.The aralkyl that the so-called identical or different more than one substituting group that can be selected from imino-and halogen atom replaces is (imino--halogenation phenyl) methyl for example.What is called can be by C
1-6The aryl sulfonyl that alkyl replaces is a p-toluenesulfonyl for example.Single C
1-6Alkyl-carbamoyl or two C
1-6C in the alkyl-carbamoyl
1-6Alkyl is preferably C
1-4Alkyl.)；
F ' 11.-N=CR
57(N (R
58) (R
58')) (R
57Be preferably hydrogen atom or C
1-4Alkyl, R
58And R
58' identical or different, preferably hydrogen atom or C
1-4Alkyl.)；
12. 5 yuan of F ' or the monocyclic aromatic heterocycle of the hexavalent (base that preferably following formula is represented.)；
F ' 13. is constituting C
7-14Bonded methylene radical dioxy base on adjacent two carbon atoms of the phenyl ring of aralkyl (for example, benzyl or styroyl);
8 '. be selected from the C of identical or different more than one substituting group replacement that condenses the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent and these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, five yuan or the monocyclic aromatic heterocycle of hexavalent are pyrryl for example, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, 1,2, the 4-triazolyl, 1,2, the 3-triazolyl, tetrazyl, 1,3,4- di azoly, 1,2,4- di azoly, 1,3, the 4-thiadiazolyl group, 1,2, the 4-thiadiazolyl group, the furazan base, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, 1,3, the 5-triazinyl, imidazolinyl, pyrazolinyl, azoles quinoline base (2- azoles quinoline base, 3- azoles quinoline base, 4- azoles quinoline base), different azoles quinoline base, thiazolinyl, the isothiazoline base, pyranyl, 2-oxo pyranyl, 2-oxygen-2,5-dihydrofuran base, preferred pyrryl, furyl, thienyl, imidazolyl, pyrazolyl, azoles base, different azoles base, thiazolyl, isothiazolyl, pyridyl, 2-oxygen-2,5-dihydrofuran base, in addition, to condense the aromatic heterocycle of formation be benzofuryl for example for these aromatic heterocycles and phenyl ring, isobenzofuran-base, benzo [b] thienyl, indyl, pseudoindoyl, the 1H-indazolyl, benzimidazolyl-benzoxazolyl, benzothiazolyl, 1H-benzotriazole base, quinolyl, isoquinolyl, cinnolinyl, quinazolyl, quinoxalinyl, phthalazinyl.
More preferably C
1-6Moieties is C such as methyl, ethyl, propyl group
1-4Alkyl, and aromatic heterocycle is a heterocyclic radical as described below.
These aromatic heterocycles are not particularly limited, preferred especially pyridyl, azoles base, triazolyl.
In addition, this aromatic heterocycle or condense the substituting group that aromatic heterocycle can be selected from more than 1 of following group of G ', preferred 1-3 and replace.)；
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl, (preferred C
1-4Alkyl.)；
[group g ']
G ' is halogen atom, (for example, fluorine atom, chlorine atom, preferred fluorine atom 1..)；
G ' is amino 2.;
The 3. single C of g '
1-6Alkylamino, (single C such as preferable methyl amino, ethylamino, propyl group amino
1-4Alkylamino.)；
G ' is two C 4.
1-6Alkylamino, (two C such as preferred dimethylamino, diethylamino
1-4Alkylamino.)；
G ' 5.C
1-6Alkoxycarbonyl amino, (for example, methoxycarbonyl amino, ethoxy carbonyl amino, propoxycarbonyl amino, isopropoxy carbonyl amino etc., preferred (C
1-4Alkoxyl group) carbonylamino.)；
And
G ' is oxyimino 6.;
G ' is halogen atom, (for example, fluorine atom, chlorine atom, preferred fluorine atom 2..)；
The C that G ' 3. can be replaced by halogen atom
1-6The alkoxyl group, (C that preference such as trifluoro ethoxy etc. are replaced by an above fluorine atom or chlorine atom
1-4Alkoxyl group.)；
G ' is aryloxy, (preferred phenoxy group 4..)；
G ' is cyano group 5.;
G’6.-N(R
59a)(R
59a’)
(wherein, R
59aAnd R
59a' identical or different, preferably hydrogen atom or C
1-4Alkyl, R
59aAnd R
59a' with five yuan or the monocyclic saturated heterocyclyl of hexavalent that adjacent nitrogen-atoms forms, preferred pyrrolidyl, imidazolidyl, pyrazolidyl, piperazinyl, piperidyl, morpholino base, thiomorpholine are for base.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-4Alkylamino and two C
1-4The more than one substituting group of alkylamino replaces.)；
G’7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, monocyclic saturated heterocyclyl such as form with adjacent nitrogen-atoms five yuan or hexavalent pyrrolidyl, imidazolidyl, pyrazolidyl, piperidyl, piperazinyl, morpholino base, thiomorpholine Dai Ji or the C that can be replaced by this heterocyclic radical
1-4Alkyl.)；
G ' is aryl, (for example, preferred phenyl 8..)；
And
Five yuan of 9. can be replaced by oxygen base or sulfenyl of G ' or the monocyclic aromatic heterocycle of hexavalent (pyridyl for example, pyridazinyl, imidazolyl, pyrimidyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl, isoquinolyl, tetrazyl, furyl, thienyl, different azoles base, thiazolyl, azoles base, isothiazolyl, pyrryl, indyl, benzimidazolyl-, benzofuryl, cinnolinyl, indazolyl, the indolizine base, phthalazinyl, pyridazinyl, triazinyl, pseudoindoyl, purine radicals, the di azoly, thiazolyl, thiadiazolyl group, the furazan base, benzo furazan base, benzothienyl, the benzotriazole base, benzothiazolyl, the benzoxazol base, quinazolyl, quinoline quinoline base, naphthyridinyl, the dihydroquinoline base, benzofuryl, furopyridinyl, pyrrolo-pyrimidine radicals, and azaindolyl
Be preferably as follows described aromatic heterocycle.)
In addition, above-mentioned R
4And R
5Can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms:
(wherein, should " saturated heterocyclic " can have two keys in the part, can also condense the formation fused rings with phenyl ring.For example, saturated heterocyclyl such as pyrrolidyl, imidazolidyl, pyrazolidyl, piperidyl, piperazinyl, morpholino base, thiomorpholine Dai Ji or these saturated heterocyclyls and phenyl ring condense 4H-quinazolyl of formation etc.Be preferably the base of representing with following formula.
In addition, these saturated heterocyclyls can be selected from halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, carboxyl and C
1-4The more than one substituting group of alkoxy carbonyl replaces.)
The preferred concrete example of The compounds of this invention (I) as described later among the embodiment put down in writing.Particularly preferred pyrazole compound is the compound that for example is selected from following compound, but is not limited to this.
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides 3/2 hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides L-(+)-tartrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl) acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diethylamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-cyclohexyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenoxy group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two fluoro-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-trifluoromethyl-benzamide
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-the benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-tertiary butyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-dimethylamino-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-sec.-propyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-6-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-oxyethyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(pyridin-3-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1H-benzimidazolyl-2 radicals-ylmethyl)-acid amides dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-ritalin,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-methyl propionate
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-pair-(2-acetoxyl group ethyl)-amino-ethyl formamyl]-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-hydroxyl-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-{2-[(2-acetoxyl group ethyl)-(2-hydroxyethyl)-amino]-the ethylamino formyl radical }-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-benzimidazolyl-2 radicals-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzothiazole-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-pyrroles-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,4-dimethoxy-pyridine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (the 5-tertiary butyl-thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-2-phenyl-2H-[1,2,3] triazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(tert-butoxycarbonyl-amino)-methyl-pyridine-2-ylmethyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-methyl-2-(morpholine-4-yl)-thiazole-5-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides 3/2 hydrochloride 1/2 hydrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethoxy carbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibenzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (cyano group-phenyl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hydroxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl amide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid allyl group-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(1-methyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [(3,4-methylenedioxyphenyl base)-methyl]-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(4-hydroxyl-butyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibutyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid is two-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopentyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(3-methoxyl group-propyl group)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-oxyethyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-isopropoxy-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-propoxy--ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethyl-propyl group)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-tert-butoxycarbonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethanoyl-piperidin-4-yl)-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-methylsulfonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-ethoxalyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxalic acid one acyl group-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1,1-dioxy-six hydrogen-1 λ
6-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxygen-six hydrogen-1 λ
4-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid propyl group-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-formamyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-oxalic acid one acyl group-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-carboxyl ethanoyl-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(2-carboxypropanoyl)-piperidin-4-yl]-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclobutyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl methyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-carboxyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-ethoxy carbonyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1H-pyrazol-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridine-2-base-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-3-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-4-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid pyrazine-2-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-methyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-hydroxyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-methyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-hydroxyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two bromo-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethyl-2-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-ethyl-4-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ([2,2 '] dithio phenyl-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methoxyl group-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl- azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hexyl-4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-thiene-3-yl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-2-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-4-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-hexyl-2-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenyl-thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenoxy group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(pyridin-3-yl)-ethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (xenyl-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1R, 2S)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1S, 2R)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-2-pyridone-3-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-piperazine-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid styroyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-styroyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroisoquinoline-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroquinoline-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid amyl group-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diphenyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridine-2-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (furans-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxycarbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-trifluoromethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-dimethylamino-ethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,6-dimethoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxycarbonyl methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-carboxyl methoxyl group-benzamide,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-difluoro benzoyl amino)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides,
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid sec.-propyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (ethoxy carbonyl-methyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (carboxyl-methyl)-phenyl-acid amides,
5-(2-chloro-4-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-oxygen-2-(piperidines-1-yl)-ethyl]-phenyl-acid amides,
5-(5-fluoro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-methoxyl group-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-ethyl)-phenyl-acid amides,
5-(2-fluoro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-2,6-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-3-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethylamino formyl radical methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isobutyl--phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxycarbonyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-ethoxy carbonyl-propyl group)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-carboxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-propyl group)-phenyl-acid amides,
5-(2-hydroxyl-4-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-hydroxy-5-methyl oxygen base-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-hydroxyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-phenyl-acid amides,
5-(2,5-dimethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-pyridine-2-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,6-two chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl-phenyl)-acid amides,
5-(2-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-6-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-pyridine-4-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(morpholine-4-base formamyl)-benzamide dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-acetic acid sodium salt,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-propionic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(morpholine-4-base formamyl)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[2-(morpholine-4-yl)-ethylamino formyl radical]-the pyridin-4-yl methyl }-the acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-base formamyl)-pyridin-4-yl methyl]-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides 1/2 vitriol
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-amino methyl-pyridine-2-ylmethyl)-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dimethanesulfonate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(morpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-diethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-2-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 5-methyl-pyrazine-2-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-methylpiperazine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-dimethylamino-piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(tetramethyleneimine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ 6-thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid carbamyl ylmethyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formamyl-phenyl)-methyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(4-methylamino formyl radical-phenyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formyl-dimethylamino-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(4H-[1,2,4] triazole-3-yl)-phenyl]-amide hydrochloride,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(N-hydroxyl carbamimidoyl)-phenyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-2,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2,2-dimethyl-propionyl oxygen base)-methoxycarbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[N-(methoxyl group-thiocarbonyl oxygen base)-carbamimidoyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-sulfo--4,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-4,5-dihydro-[1,2,4] thiadiazoles-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(cyclohexyl oxygen base-ketonic oxygen base)-ethoxy carbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-thiazol-2-yl)-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-cyano group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(toluene-4-sulfuryl amino)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-6-fluoro-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-4,5-two fluoro-benzamide hydrochloride salts,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (7-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-4H-quinazoline-3-yl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-2-methyl isophthalic acid, 4-dihydro-2H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(N-hydroxyl carbamimidoyl)-pyridin-4-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(5-oxygen-4,5-dihydro-[1,2,4] diazole-3-yl)-pyridin-4-yl methyl]-acid amides,
4-{[5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,6-two chloro-5-fluoro-pyridine-3-carbonylaminos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-benzo [b] thiophene e-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-benzoyl-amido-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-phenyl acetyl amino-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-amino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methylsulfonyl amino-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-acetylamino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3,4,5-three chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(1H-tetrazolium-5-yl)-pyridin-4-yl methyl]-acid amides and
1H-pyrazoles-3,5-dicarboxylic acid 3-benzamide 5-[(2,4-two chloro-phenyl)-acid amides].
So-called " admissible salt on its pharmacology " so long as with the salifiable material of pyrazole compound shape with general formula of the present invention (I) structure just can be any salt, for example, can enumerate following salt.Can enumerate halogen acid salts such as hydrochloride, hydrobromate, hydriodate; Inorganic acid salts such as nitrate, perchlorate, vitriol, phosphoric acid salt; Lower alkane sulfonate such as mesylate, fluoroform sulphonate, esilate; Arylsulphonate such as benzene sulfonate, tosilate; Organic carboxylates such as acetate, malate, fumarate, succinate, Citrate trianion, ascorbate salt, tartrate, oxalate, maleate; And amino acid salts such as glycinate, lysine salt, arginic acid salt, ornithine salt, glutaminate, aspartate etc.In addition, can enumerate an alkali metal salts such as sodium salt, sylvite, lithium salts; Alkali earth metal salt such as calcium salt, magnesium salts; Metal-salts such as aluminium salt; Inorganic salt such as ammonium salt; Tert-Octylamine salt, dibenzyl amine salt, alkylbenzyldimethylasaltsum saltsum, glucosamine salt, phenylglycocoll alkyl ester salt, ethylenediamine salt, N-methylglucosamine (glucamine) salt, guanidinesalt, diethyl amine salt, triethylamine salt, dicyclohexyl amine salt, N, amine salt such as organic salt such as N '-dibenzyl ethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl styroyl amine salt, piperazine salt, tetramethyl ammonium salt, three (methylol) aminomethane salt; Can there be various isomer in the compound of general formula of the present invention (I) expression, for example, and optical isomer, steric isomer, geometrical isomer, tautomer etc.Scope of the present invention comprises isomer that these are all and composition thereof.
Can with the method that oneself knows, derive its ester or other derivative, its prodrug (prodrugs) and metabolite by pyrazole derivatives with general formula of the present invention (I).
In addition, can there be various solvates (for example, hydrate) in admissible salt on The compounds of this invention or its pharmacology.Scope of the present invention comprises these solvates.
" prodrug " described in the present invention is to have the base that can carry out chemistry or metabolism decomposition, decomposes by hydrolysis or solubilizing agent, perhaps shows the derivative of the The compounds of this invention (I) of pharmaceutical active under physiological condition by decomposition.For example, can enumerate hydroxyl with respect to compound ,-CO-alkyl ,-the COO-alkyl ,-the CONH-alkyl ,-the CO-thiazolinyl ,-the COO-thiazolinyl ,-the CONH-thiazolinyl ,-the CO-aryl ,-the COO-aryl ,-the CONH-aryl ,-the CO-heterocycle ,-the COO-heterocycle ,-the CONH-heterocycle (this alkyl, thiazolinyl, aryl, heterocycle can by halogen atom, alkyl, hydroxyl, alkoxyl group, carboxyl, amino, amino acid ,-PO
3H
2,-SO
3H ,-OPO
3H
2,-OSO
3Replacements such as H.) ,-CO-polyoxyethylene glycol residue ,-COO-polyoxyethylene glycol residue ,-CO-polyalkylene glycol monoalkyl ether residue ,-COO-polyalkylene glycol monoalkyl ether residue or-PO
3H
2Deng the material that replaces formation, and with respect to the amino of compound ,-CO-alkyl ,-the COO-alkyl ,-the CO-thiazolinyl ,-the COO-thiazolinyl ,-the COO-aryl ,-the CO-aryl ,-the CO-heterocycle ,-the COO-heterocycle (this alkyl, thiazolinyl, aryl, heterocycle can by halogen atom, alkyl, hydroxyl, alkoxyl group, carboxyl, amino, amino acid ,-PO
3H
2,-SO
3H ,-OPO
3H
2,-OSO
3Replacements such as H.) ,-CO-polyoxyethylene glycol residue ,-COO-polyoxyethylene glycol residue ,-CO-polyalkylene glycol monoalkyl ether residue ,-COO-polyalkylene glycol monoalkyl ether residue or-PO
3H
2Deng the material that replaces formation, perhaps with respect to the carboxyl of compound, alkoxyl group, aryloxy (this alkoxyl group, aryloxy can by halogen atom, alkyl, hydroxyl, alkoxyl group, carboxyl, amino, amino acid ,-PO
3H
2,-SO
3H ,-OPO
3H
2,-OSO
3Replacements such as H.), polyoxyethylene glycol residue or polyalkylene glycol monoalkyl ether residue etc. replace the material of formation.
Pyrazole compound of the present invention or its salt, its ester or other derivative, its prodrug and metabolite or hydrate, solvate can be with after pharmaceutically permissible carrier mix, as solid preparations such as tablet, capsule, granular preparation, powder formulations, perhaps as aqueous preparations such as syrup, injections, per os or parenteral admin.
In this specification sheets so-called " pharmaceutical composition " be meant as pyrazole compound or its pharmaceutically permissible salt, its ester or other derivative, its prodrug and metabolite or hydrate, the solvate of effective constituent be used to make vehicle, lubricant, the wedding agent of solid preparation or be used to make aqueous preparation solvent, dissolving auxiliary, hang the uniform mixture of the third compositions such as floating agent, isotonic agent (isotonizingagent), buffer reagent.
No matter administration is the oral administration that utilizes tablet, pill, capsule, granular preparation, powder formulation, liquid preparation etc., still utilize intravenous injection, intramuscular injection etc. injection, suppository, can through skin with which kind of mode of the parenteral admin of preparation etc.As this parenteral admin, can enumerate in intravenously, intramuscular, subcutaneous, the tissue, nasal cavity, intracutaneous, point are instilled into, in the brain, in the internal rectum, anus, intraperitoneal administration etc.
As " being used for peroral administration solids composition " of the present invention, can use tablet, powder formulation, granular preparation etc.In this kind solids composition, more than one active substance quilt and at least a inert excipients, for example mixing such as lactose, N.F,USP MANNITOL, glucose, hydroxypropylcellulose, Microcrystalline Cellulose, starch, Polyvinylpyrolidone (PVP), aluminum magnesium silicate.Composition also can contain inert excipient additive in addition, for example the stabilization agent of lubricant, disintegrating agent, antioxidant and so on, dissolution aids etc. according to well-established law.As required, also tablet or the pill film with sugar-coat such as sucrose, gelatin, hydroxypropylcellulose, Vltra tears, hydroxypropyl methyl cellulose phthalate, macrogol, titanium dioxide, talcum or gastric solubility or enteric solubility can be covered.
" be used for peroral administration liquid composition " and contain pharmaceutically permissible emulsion, liquor, suspension agent, syrup, elixir (elixirs) etc., contain the inert solvent of general use, for example pure water, ethanol.Said composition can also contain auxiliary, sweeting agent, correctives, perfume compound, the preservatives of solubilizing agent, wetting agent, outstanding floating agent and so on except the inert solvent.
As " injection that is used for parenteral admin ", can be by (for example polysorbate 80 with a certain amount of effective constituent and dispersion agent, polyoxyethylene hardened castor oil 60, polyoxyethylene glycol, carboxymethyl cellulose, sodiun alginate etc.), preservatives (methyl p-Hydroxybenzoate for example, propyl para-hydroxybenzoate, benzylalcohol, butylene-chlorohydrin, phenol etc.), isotonic agent (sodium-chlor for example, glycerine, D-N.F,USP MANNITOL, the D-Sorbitol Powder, glucose etc.) etc. dissolving together,, suspend or be emulsifiable in aqueous solvent (distilled water for injection for example, physiological saline, Ringer's solution etc.) or oil-based solvent (sweet oil for example, sesame oil, Oleum Gossypii semen, corn wet goods vegetables oil, propylene glycol etc.) etc. make in.At this moment, also can be as required, use additives such as dissolving auxiliary (for example sodium salicylate, sodium acetate etc.), stablizer (for example human serum protein etc.), soothing agent (soothing agent, for example benzylalcohol etc.).Can also contain antioxidant, tinting material etc. or other additive as required.
As " pharmaceutically permissible carrier ", can enumerate as preparation material and habitual various organic or inorganic carrier substance, in solid preparation, can suitably cooperate vehicle, lubricant, wedding agent, disintegrating agent etc., in addition, in aqueous preparation, can suitably cooperate solvent, dissolving auxiliary, outstanding floating agent, isotonic agent, buffer reagent, soothing agent etc.In addition, as required, also can use preparation additives such as sanitas, antioxidant, tinting material, sweeting agent, sorbent material, gelating agent according to well-established law.
As the suitable example of " vehicle ", can enumerate for example lactose, W-Gum, white sugar, D-N.F,USP MANNITOL, D-Sorbitol Powder, starch, dextrin, crystal fibre element, low degree of substitution hydroxypropyl cellulose, Xylo-Mucine, gum arabic, glucose, silicon-dioxide etc.
As the suitable example of " antioxidant ", for example can enumerate sulphite, xitix etc.
As " disintegrating agent ", for example can use carboxymethyl cellulose, calcium carboxymethylcellulose, carboxymethylstach sodium, crosslinked sodium cellulose glycolate (crosscarmellose sodium), polyvinylpolypyrrolidone (crosspovidone), low degree of substitution hydroxypropyl cellulose, hydroxypropylated starch etc.
As " wedding agent ", for example can enumerate hydroxypropylcellulose, Vltra tears, Polyvinylpyrolidone (PVP), crystal fibre element, white sugar, gum arabic powder etc.Preferred hydroxypropylcellulose of wedding agent or Polyvinylpyrolidone (PVP).
As the suitable example of " lubricant ", for example can enumerate Magnesium Stearate, calcium stearate, talcum, colloidal silica etc.
As the suitable example of " isotonic agent ", for example can enumerate glucose, D-Sorbitol Powder, sodium-chlor, glycerine, D-N.F,USP MANNITOL etc.
As " pH adjusts agent ", can enumerate Citrate trianion, phosphoric acid salt, carbonate, tartrate, fumarate, acetate, amino acid salts etc.
As the suitable example of " dissolving auxiliary ", for example can enumerate polyoxyethylene glycol, propylene glycol, D-N.F,USP MANNITOL, peruscabin, ethanol, Trisaminomethane, cholesterol, trolamine, yellow soda ash, Trisodium Citrate etc.
As the suitable example of " solvent ", for example can use water for injection, ethanol, propylene glycol, polyoxyethylene glycol (macrogol), sesame oil, Semen Maydis oil, olive wet goods.
Suitable example as " outstanding floating agent " for example can example illustrate hydrophilic macromolecules such as polyvinyl alcohol, Polyvinylpyrolidone (PVP), Xylo-Mucine, methylcellulose gum, Walocel MT 20.000PV, Natvosol, hydroxypropylcellulose etc.
As the suitable example of " tensio-active agent ", for example can enumerate Sodium Lauryl Sulphate BP/USP, lauryl alanine, Yelkin TTS (lecithin), benzalkonium chloride (benzalkonium chloride), benzethonium chloride (benzethonium chloride), Zerol etc.
As the suitable example of " soothing agent ", for example can enumerate benzylalcohol etc.
As the suitable example of " buffer reagent ", for example can enumerate the damping fluid of phosphoric acid salt, acetate, carbonate, Citrate trianion etc. etc.
As the suitable example of " preservatives ", for example can enumerate parabens, butylene-chlorohydrin, benzylalcohol, styroyl alcohol, dehydroacetic acid (DHA), Sorbic Acid etc.
When the present invention is used as the treatment of diabetes agent, can be in whole body or part, per os or parenteral admin.Dosage is according to the difference of age, body weight, symptom, result of treatment etc. and difference, and everyone the 1 time amount of being grown up usually is the scope of 10mg-1g, administration in 1 day 1 time～for several times.
The compounds of this invention (I) can mix suitable dilution agent, dispersion agent, sorbent material, solvating agent etc., so that be formed for peroral administration solids composition and liquid composition, perhaps is used for the preparations such as injection of parenteral admin.
In addition, The compounds of this invention (I) can be used for the treatment of or prevent human diabetes, can certainly be used for the treatment of or prevent the animal except the mankind, for example mammiferous diabetes.
The compounds of this invention (I) can be used in the usual way that medical aspect usually adopts, and is used in combination with other medicament of 1 dose or multi-agent.Can have with the medicament of The compounds of this invention (I) and usefulness multiple, preferred especially remedy for hyperlipemia, Remedies for diabetes.Here, so-called is the also usefulness of medicament and other more than one medicaments of effective constituent with being meant with The compounds of this invention (I) also, is not particularly limited.Other medicament can be to have and be the identical drug effect of medicament of effective constituent, the medicine of the mechanism of action with The compounds of this invention (I), also can be to have different drug effects, the medicine of the mechanism of action.These medicaments can perhaps also can be used as the mixture administration respectively as independent preparation administration.As required, also these preparations can be combined to form test kit.In addition, for delivery time, also be not particularly limited, can be with the administration simultaneously of two kinds of preparations, time administration also can stagger.
Compound of the present invention, pharmaceutical composition or medicament can with other pharmaceutical composition or medicament (below, be also referred to as and with medicament) and use.
Pharmaceutical composition of the present invention or medicament and and the delivery time of with medicament without limits, can be with these medicines with respect to the administration object, administration simultaneously also can separate the time difference administration.And the dosage of with medicament is as long as abide by the dosage of using clinically, can be according to suitably selections such as age of administration object, administration object and body weight, symptom, administration time, agent shape, medication, combinations.And the form of medication of with medicament is not particularly limited, during administration with pharmaceutical composition of the present invention or medicament and and the with medicament combination get final product.
As and with medicament, can enumerate
(1) treatment of hyperlipidaemia or preventive,
(2) treatment of obesity or preventive,
(3) treatment of diabetes or preventive,
(4) treatment of diabetic complications or preventive,
(5) treatment of vascular hypertension or preventive,
Medicament and the The compounds of this invention of 1-3 can be used in combination.
As " treatment of hyperlipidaemia or preventive ", can for example enumerate
(1) fibrates class medicament (PPAR α receptor stimulant),
(2) the PPAR delta receptor agonist,
(3) microsomal triglyceride transfer protein (MTP) inhibitor,
(4) cholesteryl ester transfer protein (CETP) inhibitor,
(5) statins class medicament (HMG-CoA reductase inhibitor),
(6) anionite-exchange resin,
(7) probucol,
(8) nicotinic acid class medicament,
(9) plant sterol,
(10) apolipoproteins-A1 (Apo-A1) inductor,
(11) lipoprotein lipase (LPL) activator,
(12) the endodermis lipase inhibitor,
(13)ezetimibu、
(14) ibat inhibitor,
(15) inhibitor for squalene synthetic enzyme,
(16) the ACAT inhibitor,
(17) the lxr receptor agonist,
(18) the FXR receptor stimulant,
(19) the FXR receptor antagonist,
(20) adenosine A 1 agonist,
Particularly, can enumerate clofibrate, bezafibrate, fenofibrate, lovastatin (lovastatin), Simvastatin (simvastatin), Pravastatin (pravastatin), fluvastatin (fluvastatin), atorvastatin (atorvastatin), pitavastatin, rosuvastatin, Cerivastatin (cerivastatin), Colestyramine, the courage ammonium fat (colestimide) that disappears, tocopheryl nicotinate, nicomol, pentaerythritol tetranicotinate, stigmasterol (soysterol) or γ orizanol etc.
As " treatment of obesity or preventive ", can for example enumerate
(1) the leptin preparation,
(2) pancreatic lipase inhibitor,
(3) the norepinephrine serotonin reuptake inhibitors,
(4) the cannabinoid receptor antagonist,
(5) monoamine re-uptake inhibitor,
(6) triglyceride acyltransferase (DGAT) inhibitor,
(7) glucose dependency insulin secretion promote polypeptide (GIP) receptor antagonist,
(8) the leptin receptor stimulant,
(9) bombasin receptor subtype 3 (BRS-3) agonist,
(10) the perilipin inhibitor,
(11) acetyl-CoA carboxylase 1 (ACC1) inhibitor,
(12) acetyl-CoA carboxylase 2 (ACC2) inhibitor,
(13) Fatty acid synthetase (fatty acid synthase) inhibitor,
(14) sn-1-acyl group-glycerol-3-phosphate acyltransferase (AGPAT) inhibitor,
(15) pancreatic phospholipase A2 (pPLA2) inhibitor,
(16) melanocortin (MC) receptor stimulant,
(17) neuropeptide Y 5 (NPY5) receptor antagonist,
(18) Uncoupling Proteins (UCP) inductor or activator,
(19) CPT1 (CPT-1) activator,
(20) CCK1 (CCKA) agonist,
(21) ciliary neurotrophic factor (CNTF),
(22) the CRF2 agonist,
(23) neuropeptide Y 2 (NPY2) receptor antagonist,
(24) neuropeptide tyrosine 4 (NPY4) receptor antagonist,
(25) the Thyroid Hormone Receptors beta-agonists,
(26) the growth hormone,
(27) the atp citrate lyase inhibitors,
(28) the 5-HT6 antagonist,
(29) 5-HT2C agonist,
Particularly, can enumerate leptin, orlistat (orlistat), sibutramine (sibutramine), rimonabant or Mazindol etc.
As " treatment of diabetes or preventive ", can for example enumerate
(1) insulin preparation (injection),
(2) low molecule oral insulin agent,
(3) sulfonylurea receptor stimulant (SU agent),
(4) the non-sulfonylurea insulin secretion stimulators,
(5) potassium dependency ATP (KATP) access portal agent,
(6) the α alpha-glucosidase inhibitors,
(7) the αDian Fenmei inhibitor,
(8) insulin sensitivity enhancer,
(9) low molecule tGLP-1 receptor stimulant,
(10) the tGLP-1 peptide analogs,
(11) DPP IV (DPP-IV) inhibitor,
(12) glucagon receptor antagonist,
(13) glucocorticoid receptor antagonists,
(14) biguanides agent,
(15) the SGLUT inhibitor,
(16) fructose-1,6-bisphosphatase (FBPase) inhibitor,
(17) Glycogen Synthase kinase 3 (GSK-3) inhibitor,
(18) phosphoenolpyruvate carboxykinase (PEPCK) inhibitor,
(19) protein tyrosine phosphatase esterase 1B (protein tyrosine phosphatase1B, PTPase 1B) inhibitor,
(20) contain the SH2 zone inositol monophosphate esterase (SHIP2) inhibitor,
(21) glycogen phosphorylase (GP) inhibitor,
(22) glucokinase activators,
(23) the GPR40 receptor stimulant,
(24) pyruvic dehydrogenase kinase (PDHK) inhibitor,
(25) glutamine: fructose-6-phosphate transaminase (GFAT) inhibitor,
(26) antioxidant; Nitric oxide scavengers,
(27) carnitine palmityl transferase 1 (CPT-1) inhibitor,
(28) growth releasing factor (GHRF),
(29) triacylglycerol lipase (hormone-sensitive lipase) inhibitor,
(30) PPAR γ receptor stimulant,
(31) PPAR γ receptor antagonist,
(32) PPAR α/γ receptor stimulant,
(33) AMP-sensitization protein kinase (AMPK) activator,
(34) the adiponectin receptor stimulant,
(35) β
3Adrenoceptor agonists,
Particularly, can enumerate Regular Insulin, tolbutamide, glyclopyramide, tsiklamid (acetohexamide), P-607, glybuzole, Glyburide, gliclazid, gsh, mitiglinide, repaglinide (repaglinide), nateglinide, voglibose (voglibose), acarbose, miglitol (miglitol), rosiglitazone maleate (rosiglitazone maleate), Walaphage, U-72107A (pioglitazone hydrochloride) or Ziavetine etc.
As " treatment of diabetic complications or preventive ", can for example enumerate
(1) protein kinase β (PKC β) inhibitor,
(2) angiotensin II receptor antagonists,
(3) aldose reductase inhibitor,
(4) angiotensin-converting enzyme (ACE) inhibitor,
(5) saccharification final product (AGE) produce inhibitor,
(6) neuropathy remedies,
(7) diabetic nephropathy therapeutical agent,
Particularly, can enumerate epalrestat (epalrestat, Kinedak), mexiletine hydrochloride and hydrochloric acid imidapril (imidapril hydrochloride) etc.
As " treatment of vascular hypertension or preventive ", can for example enumerate
(1) thiazide diuretic,
(2) the similar diuretic(s) of thiazides,
(3) loop diuretic,
(4) K retentivity diuretic(s),
(5) Beta receptor blockers,
(6) α, Beta receptor blockers,
(7) alpha blocker,
(8) the central sympathetic inhibitor,
(9) tip sexual intercourse sense nerous sedative (Radix Rauvolfiae preparation),
(10) Ca antagonist (benzothiazepin class),
(11) Ca antagonist (dihydropyridines),
(12) vasodilator,
(13) angiotensin-converting enzyme (ACE) inhibitor,
(14) angiotensin II receptor antagonists,
(15) nitric acid agent,
(16) endothelin ETA receptor antagonist,
(17) endothelin-converting enzyme inhibitor neprilysin inhibitor,
(18) prostaglandin(PG); Prostanoid FP agonist,
(19) hypertension fibrinogen inhibitor,
(20) NOS3 expresses intensifying factor; The prostacyclin analogue,
(21) Phosphodiesterase V (PDE5A) inhibitor,
(22) the prostacyclin analogue,
(23) aldosterone antagonist,
Particularly, can enumerate Zestoretic, trichloromethiazide, the Wyovin Zestoretic, the sulphonamide chroman, indapamide, tripamide, chlortalidone, Mefrusal, furosemide, antisterone, triamterene, Target, bisoprolol fumarate (bisoprolol fumarate), the hydrochloric acid betaxolol, bevantolol hydrochloride, metoprolol tartrate, Acebutolol, Celiprolol Hydrochorid (celiprolol hydrochloride), nipradolol (nipradilol), N-696 (tilisololhydrochloride), nadolol, propranolol hydrochloride, hydrochloric acid indenolol (indenololhydrochloride), carteolol hydrochloride (carteolol hydrochloride), pindolol, pindolol continues releasing agent, Betriol (Boehringer,Ing.), penbutolol sulfate (penbutolol sulfate, penbutolol sulfate), bopindolol malonate, amosulalol hydrochloride (amosulalolhydrochloride), arotinolol hydrochloride, carvedilol (carvedilol), labetalol hydrochloride, urapidil, Vasocard, the methylsulfonic acid element, E-643, PRAZOSINI HYDROCHLORIDE, phentolamine mesilate (phentolamine mesilate), Tenso-Timelets (clonidinehydrochloride), guanidine hydrochloride method new (guanfacine hydrochloride), guanabenz acetate (guanabenz acetate), methyldopa, serpentine, rescinnamine, Phenylsulfonic acid A Muluohe (amlodipine besylate), Aranidipine (aranidipine), efonidipine (efonidipinehydrochloride), cilnidipineb (cilnidipine), nicardipine hydrochloride (nicardipinehydrochloride), nisoldipine (nisoldipine), nitrendipine, nifedipine, nifedipine continues releasing agent, nilvadipine (nilvadipine), Bamidipine Hydrochloride (barnidipinehydrochloride), felodipine (felodipine), KW-3049 (benidipinehydrochloride), CV-4093 (manidipine hydrochloride), Azelnidipine (azelnidipine), diltiazem hydrochloride, hydrazine hydrochloride, todoralazine hydrochloride, budralazine, cadralazine (cadralazine), captopril, enalapril maleate (enalapril maleate), alacepril (alacepril), delapril hydrochloride (delapril hydrochloride), Yipingshu (cilazapril), lisinopril (lisinopril), benazepril hydrochloride (benazeprilhydrochloride), hydrochloric acid imidapril (imidapril hydrochloride), tamocaprilhydrochloride, quinapril hydrochloride (quinapril hydrochloride), Trolapril (trandolapril), perindopril erbumine, candesartan cilexetil, valsartan (valsartan), telmisartan (telmisartan), olmesartan medoxomil, sodium nitroprusside (sodium nitroprusside), and nitroglycerine (nitroglycerine) etc.
Below, the preparation method of the pyrazole compound of compound (1) expression is described, but preparation method of the present invention is not limited to this.As long as the usage quantity of the solvent that each operation is used can stirred reaction mixture, be not particularly limited.In addition, in each operation, reaction can be implemented according to the method for carrying out usually, can be with ordinary method, for example recrystallization, redeposition or be customarily used in organic compound segregation purified method usually, for example adsorpting column chromatogram method, partition column chromatography, ion exchange chromatography, utilize the method appropriate combination of gel-filtration to emanate, refining.Below, the preparation method who relates to the compound that general formula of the present invention represents is specifically described, still, much less the present invention is not limited to these preparation methods.Therefore, The compounds of this invention can ((C-1～C-6) be prepared also can perhaps be prepared with reference to these preparation methods according to embodiment described later for A-1～A-3), B or C according to following preparation method A.During the preparation The compounds of this invention, reaction sequence can appropriate change.Get final product according to thinking that rational operation is reacted.In addition, if desired, can carry out due care, deprotection.If desired, can suitably carry out the reaction in addition of each operation.For the carrying out that promotes to react, can suitably utilize illustrative reagent reagent in addition.
Following preparation section flow process is representative preparation method's a example, but preparation method of the present invention is not particularly limited to following method.The compound that is obtained by each operation can be emanated and makes with extra care with ordinary method, still, can not emanate refining sometimes and carries out next operation.
Preparation method A (preparation method A-1～A-3):
Preparation method A is as follows.Each symbol in the reaction formula and above-mentioned synonym.Below identical.
The 1st operation; The preparation of compound (A2)
By nitro with compound (A1), in solvent, in the presence of catalyzer, be amino with hydrogen reduction, can obtain compound (A2).
As the solvent that uses in the reaction, can enumerate for example alcoholic solvent such as methyl alcohol, ethanol; Ether solvents such as two alkane, tetrahydrofuran (THF); Esters solvents such as vinyl acetic monomer; N, dinethylformamide isopolarity solvent; Water etc., they can be used alone or as a mixture.
As the catalyzer that uses in the reaction, can enumerate for example palladium catalyst such as palladium black, palladium-carbon; How to draw nickel catalyzator such as nickel; Platinum such as platinum oxide, platinum oxide-carbon class catalyzer etc.(reference M.Hudlicky, Reductions in Organic Chemistry, Wiley-Interscience, NewYork, 1984.)
Temperature of reaction is about 0-100 ℃, preferred about 0 ℃ to room temperature.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
In addition, instead the hydrogen of hydrogen can be enumerated for example formic acid, ammonium formiate, tetrahydrobenzene, hydrazine etc. with body.(reference M.Hudlicky, Reductions in Organic Chemistry, Wiley-Interscience, New York, 1984.)
In addition, as other the method for reducing of nitro, can enumerate the reaction that for example utilizes zinc/hydrochloric acid, tin protochloride, sodium bisulfite, titanous chloride etc.(reference M.Hudlicky, Reductionsin Organic Chemistry, Wiley-Interscience, New York, 1984.)
The 2nd operation; The preparation of compound (A5)
By compound (A3) is made into compound (A4) according to common acyl chlorides synthetic method, utilize it with the amino of compound (A2) in solvent, in the presence of alkali, carry out acidylate, can obtain compound (A5).
As the reagent that uses in the acyl chlorides building-up reactions, can enumerate for example oxalyl chloride, thionyl chloride, phosphorus pentachloride etc.
In addition, can be as required, add and be used to promote the N that reacts, dinethylformamide.
In addition, if desired, can be with reaction solvent for example diethyl ether, tetrahydrofuran (THF), two alkane, 1,2-glycol dimethyl ether, diglyme ether solvents such as (diglyme); Varsols such as benzene, toluene, hexane, dimethylbenzene; Methylene dichloride, chloroform, tetracol phenixin, 1, halogenated hydrocarbon solvents such as 2-ethylene dichloride; Esters solvents such as vinyl acetic monomer, ritalin, N-BUTYL ACETATE etc. use separately or mix and use.
Temperature of reaction is-20 ℃ to 120 ℃ approximately, preferred about 0 ℃ to 80 ℃.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
As the solvent that acylation reaction is used, can enumerate for example diethyl ether, tetrahydrofuran (THF), two alkane, 1, ether solvents such as 2-glycol dimethyl ether, diglyme; Varsols such as benzene, toluene, hexane, dimethylbenzene; Methylene dichloride, chloroform, tetracol phenixin, 1, halogenated hydrocarbon solvents such as 2-ethylene dichloride; Esters solvents such as vinyl acetic monomer, ritalin, N-BUTYL ACETATE; Acetone, N,N-dimethylacetamide, dimethyl sulfoxide (DMSO) isopolarity solvent; Water etc., they can use or mix use separately.
As the alkali that uses in the reaction, can enumerate for example organic bases such as triethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine; Inorganic bases such as lithium hydroxide, sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus.
Temperature of reaction is about 0 ℃ to 120 ℃, preferred about 0 ℃ to 95 ℃.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
In addition, also can form reaction, directly make the combination of compound (A3) and compound (A2) and acquisition compound (A5) according to the amido linkage except that record here.
As operable method, can enumerate and for example utilize mixed anhydride method, acid azide method, DCC method, EDC method, EDC-HOBt method, EDC-HOSu method, other the liquid phase synthesizing method of active ester method, CDI method etc.; Peptide solid-phase synthesis etc.
(DCC:1,3-dicyclohexyl carbodiimide)
(EDC:1-ethyl-3-(3 '-dimethylaminopropyl) carbodiimide)
(HOBt:1-hydroxybenzotriazole)
(HOSu:1-N-Hydroxysuccinimide)
(CDI:1,1 '-carbonyl dimidazoles)
The 3rd operation; The preparation of compound (A6)
By with the ester group of compound (A5) in solvent, under common hydrolysising condition, form carboxylic acid, can obtain compound (A6).
As the solvent that uses in the reaction, can enumerate for example alcoholic solvent such as methyl alcohol, ethanol; Ether solvents such as two alkane, tetrahydrofuran (THF); Ketones solvents such as acetone; N, dinethylformamide, dimethyl sulfoxide (DMSO) isopolarity solvent; Water etc., they can be used alone or as a mixture.
As the alkali that uses, can enumerate for example alkali metal hydroxide such as sodium hydroxide, potassium hydroxide; Alkaline-earth metal oxyhydroxide such as hydrated barta etc.
Temperature of reaction is about 0-100 ℃, preferred about 0 ℃ to room temperature.Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
The 4th operation to the 8 operations; The preparation of compound (I)
To the 4th operation to the 8 operations, its summary has been described below.
The compound of general formula (I) expression can be by following method preparation, that is, and and the compound that the carboxyl of compound (A6) is carried out sensitization formation, for example, imidazolide (compound (A7); The the 4th, the 5th operation of preparation method A-1) isoreactivity amides; HOBt ester (compound (A8); The the 6th, the 7th operation of preparation method A-2), after HOSu ester isoreactivity ester class etc. emanates, form amido linkage with compound (A9) and prepare as amine.
In addition, can above-mentioned active carbonyl compound not emanated yet, directly utilize common amido linkage to form reaction by compound (A6), for example, based on mixed anhydride method, acid azide method, DCC method, EDC method, EDC-HOBt method, EDC-HOSu method, other the liquid phase synthesizing method of active ester method, CDI method etc.; Peptide solid-phase synthesis etc. and form amido linkage as the compound (A9) of amine and prepare (the 8th operation of following preparation method A-3).
(reference E.Gross., The Peptides, Academic Press, 1981.)
Preparation method A-1; Preparation method via the compound (I) of compound (A7)
The 4th operation: the preparation of compound (A7)
By compound (A6) is reacted with CDI, can obtain compound (A7) in solvent.
As the solvent that uses in the reaction, for example can enumerate ether solvents such as tetrahydrofuran (THF); Halogenated hydrocarbon solvents such as chloroform; Varsols such as toluene; N, dinethylformamide isopolarity solvent, they can be used alone or as a mixture.
Temperature of reaction is about 0-100 ℃, and preferred room temperature is to about 80 ℃.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
In addition, if for example use its similar compound, 1,1 '-carbonyl two (glyoxal ethyline) etc. replaces CDI, can obtain corresponding active amide class.
In addition, utilize other active amide building-up reactions, also can obtain compound (A7) or corresponding active amide class.
The 5th operation: by compound (A7) preparation compound (I)
By making compound (A7) in solvent,, can obtain the compound of general formula (I) expression with compound (A9) reaction as amine.
As the solvent that uses in the reaction, for example can enumerate ether solvents such as tetrahydrofuran (THF); Esters solvents such as vinyl acetic monomer; Halogenated hydrocarbon solvents such as chloroform; Varsols such as toluene; N, dinethylformamide isopolarity solvent etc., they can be used alone or as a mixture.
Temperature of reaction is about 0-100 ℃, be preferably about 0 ℃ to room temperature.Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
Preparation method A-2; Preparation method via the compound (I) of compound (A8)
The 6th operation: by compound (A6) preparation compound (A8)
By make compound (A6) in solvent in the presence of condensing agent, with the HOBt condensation, can obtain compound (A8) as the active ester class.
As condensing agent, can enumerate for example Carbodiimides such as EDC, DCC; Haloformate classes such as chloro ethyl formate etc.
As the solvent that uses in the reaction, for example can enumerate ether solvents such as tetrahydrofuran (THF); Esters solvents such as vinyl acetic monomer; Halogenated hydrocarbon solvents such as chloroform; Varsols such as toluene; N, dinethylformamide isopolarity solvent; Water etc., they can be used alone or as a mixture.
Temperature of reaction is about 0-100 ℃, be preferably about 0 ℃ to room temperature.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
In addition, if N-hydroxyl acid imides such as application examples such as HOSu replace HOBt, can obtain corresponding active ester class.
The 7th operation: by compound (A8) preparation compound (I)
By making compound (A8) in solvent,, can obtain the compound of general formula (I) expression with compound (A9) reaction as amine.
As the solvent that uses in the reaction, for example can enumerate ether solvents such as tetrahydrofuran (THF); Esters solvents such as vinyl acetic monomer; Halogenated hydrocarbon solvents such as chloroform; Varsols such as toluene; N, dinethylformamide isopolarity solvent; Water etc., they can be used alone or as a mixture.
Temperature of reaction is about 0-100 ℃, be preferably about 0 ℃ to room temperature.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
Preparation method A-3; The method that directly prepares compound (I) by compound (A6)
The 8th operation: by compound (A6) preparation compound (I)
The compound of general formula (I) expression can utilize common amido linkage to form reaction by compound (A6), for example mixed anhydride method, acid azide method, DCC method, EDC method, EDC-HOB method, other the liquid phase synthesizing method of active ester method, CDI method etc.; Peptide solid-phase synthesis etc. form amido linkage with suitable amine and prepare.
As the solvent that uses in the reaction, for example can enumerate ether solvents such as tetrahydrofuran (THF); Esters solvents such as vinyl acetic monomer; Halogenated hydrocarbon solvents such as chloroform; Varsols such as toluene; N, dinethylformamide isopolarity solvent; Water etc., they can be used alone or as a mixture.
Temperature of reaction is about 0-100 ℃, be preferably about 0 ℃ to room temperature.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
Preparation method B:
Preparation method B is as follows.Each symbol in the formula is same as described above.Below identical.
The 1st operation: the preparation of compound (B2)
With the acyl chlorides building-up reactions of the 2nd operation of preparation method A in the same manner, can obtain compound (B2) by compound (B1).
The 2nd operation: the preparation of compound (B4)
By making compound (B2) in solvent, in the presence of alkali,, can obtain compound (B4) as required with compound (B3) reaction.
As the solvent that uses in the reaction, can enumerate for example diethyl ether, tetrahydrofuran (THF), two alkane, 1, ether solvents such as 2-glycol dimethyl ether, diglyme; Varsols such as benzene, toluene, hexane, dimethylbenzene; Methylene dichloride, chloroform, tetracol phenixin, 1, halogenated hydrocarbon solvents such as 2-ethylene dichloride; Esters solvents such as vinyl acetic monomer, ritalin, N-BUTYL ACETATE; Acetone, N, dinethylformamide isopolarity solvent; Water etc., they can use or mix use separately.
As the alkali that uses in the reaction, can enumerate for example organic bases such as triethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine; Inorganic bases such as lithium hydroxide, sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus.
Temperature of reaction is about 0 ℃ to 120 ℃, preferred about 0 ℃ to 60 ℃.
Reaction times is about 10 minutes to 48 hours, preferred about 30 minutes to 24 hours.
The 3rd operation: the preparation of compound (B6)
With the 1st operation of preparation method A in the same manner, by with the nitro of compound (B4) in solvent, in the presence of catalyzer, use hydrogen reduction, can obtain compound (B6).
The 4th operation: by compound (B6) preparation compound (I)
With the 2nd operation of preparation method A in the same manner, by with the amino of compound (B6) in solvent, in the presence of alkali, utilize compound (A4) to carry out acidylate, can obtain the compound of general formula (I) expression.
Preparation method C: the preparation method of the salt of pyrazole compound
Preparation method C-1:
With the compound dissolution of general formula (I) expression in solvent orange 2 A, to wherein adding acid or alkali (itself or solution).It is left standstill and leaches the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
Preparation method C-2:
With the compound dissolution of general formula (I) expression in solvent orange 2 A, to wherein adding acid or alkali (itself or solution).It is concentrated and leaves standstill.Leach the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
Preparation method C-3:
With the compound dissolution of general formula (I) expression in solvent orange 2 A, to wherein adding acid or alkali (itself or solution).To wherein adding solvent B and leaving standstill.Leach the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
Preparation method C-4:
The compound of general formula (I) expression is suspended in the solvent orange 2 A, forms solution to wherein adding acid or alkali (itself or solution).It is left standstill and leaches the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
Preparation method C-5:
The compound of general formula (I) expression is suspended in the solvent orange 2 A, forms solution to wherein adding acid or alkali (itself or solution).It is concentrated and leaves standstill.Leach the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
Preparation method C-6:
The compound of general formula (I) expression is suspended in the solvent orange 2 A, forms solution to wherein adding acid or alkali (itself or solution).To wherein adding solvent B and leaving standstill.Leach the solid of separating out, thereby can obtain the salt of the compound of general formula (I) expression.
In addition, by will (the two acid salt dissolving of the preparation of C-1～C-6) or be suspended in above-mentioned solvent orange 2 A and leave standstill also can obtain an acid salt according to above-mentioned preparation method C.As two acid salt, can enumerate for example dihydrochloride, dimethanesulfonate etc., as an acid salt, can enumerate for example a hydrochloride, a mesylate etc.
In addition, among above-mentioned preparation method C-1～C-6,, can enumerate for example alcoholic solvents such as methyl alcohol, ethanol, propyl alcohol as " solvent orange 2 A " that use; Diethyl ether, tetrahydrofuran (THF), two alkane, 1, ether solvents such as 2-glycol dimethyl ether, diglyme; Varsols such as benzene, toluene, hexane, dimethylbenzene; Methylene dichloride, chloroform, tetracol phenixin, 1, halogenated hydrocarbon solvents such as 2-ethylene dichloride; Esters solvents such as vinyl acetic monomer, ritalin, N-BUTYL ACETATE; Acetone, N,N-dimethylacetamide, dimethyl sulfoxide (DMSO) isopolarity solvent; Water etc.
" solvent B " as using can enumerate for example diethyl ether, tetrahydrofuran (THF), two alkane, 1, ether solvents such as 2-glycol dimethyl ether, diglyme; Varsols such as benzene, toluene, hexane, dimethylbenzene; Methylene dichloride, chloroform, tetracol phenixin, 1, halogenated hydrocarbon solvents such as 2-ethylene dichloride; Esters solvents such as vinyl acetic monomer, ritalin, N-BUTYL ACETATE etc.
As " acid " used, can enumerate for example sulfonic acid classes such as carboxylic-acids such as inorganic acids such as hydrochloric acid, Hydrogen bromide, sulfuric acid, oxysuccinic acid, citric acid, oxalic acid, methylsulfonic acid, Phenylsulfonic acid, tosic acid.Preferred hydrochloric acid, tosic acid.As " alkali " that uses, can enumerate for example inorganic base and solution thereof such as sodium hydroxide, sodium hydride, potassium hydroxide, lime carbonate; Organic amine such as thanomin, triethylamine etc.Preferred aqueous sodium hydroxide solution.
Embodiment
Below, the present invention will be described in detail by enumerating embodiment, but the present invention is not limited by these embodiment.
Reference example 1:5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid
Imidazolide and 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzene
And triazol-1-yl)-preparation of ester;
(operation 1) 2-chloro-4, the preparation of 5-difluoro benzoyl chloride;
At 2-chloro-4, in toluene (250ml) solution of 5-difluoro-benzoic acid (508.20g), add N, dinethylformamide (0.2ml), be heated to 65 ℃ after, thionyl chloride (230ml).After stirring 3 hours under 120 ℃, reaction solution is under reduced pressure concentrated, the residue that obtains is carried out underpressure distillation (bp 51-64 ℃ (130-140Pa)), obtain oily matter title compound (534.45g).
The preparation of (operation 2) 5-nitro-3-pyrazole carboxylic acid ethyl ester;
In ethanol (3L) solution of 5-nitro-3-pyrazole carboxylic acid (310.24g), add methylsulfonic acid (143ml), stir a night down at 94 ℃.Reaction solution is under reduced pressure concentrated, in the residue that obtains, add entry (1.5L) then, then under the ice bath cooling, add wet chemical (making salt of wormwood 153.07g be dissolved in water 750ml modulates).Leach the solid of separating out, obtain white crystals title compound (343.09g).
The preparation of (operation 3) 5-amino-3-pyrazole carboxylic acid ethyl ester;
In the tetrahydrofuran (THF) (1.5L) of 5-nitro-3-pyrazole carboxylic acid ethyl ester (331.48g) and vinyl acetic monomer (1.5L) solution, add 7.5% palladium-carbon (30.036g), under hydrogen atmosphere, at room temperature stir a night.After leaching catalyzer, filtrate is under reduced pressure concentrated and with vinyl acetic monomer-hexane the solid that obtains is carried out recrystallization, acquisition white crystals title compound (265.38g).
(operation 4) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid, ethyl ester
Preparation;
In tetrahydrofuran (THF) (1.33L) solution of 5-amino-3-pyrazole carboxylic acid ethyl ester (265.38g), add pyridine (153ml).Under ice bath cooling, drip the 2-chloro-4 that the operation 1 by reference example 1 obtains in this solution, 5-difluoro benzoyl chloride (362.00g) at room temperature stirred 2 hours.Reaction mixture is under reduced pressure concentrated, carry out recrystallization with 2-propyl alcohol-water then, obtain white crystals title compound (538.85g).
The preparation of (operation 5) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid;
In the alcohol suspension (1L) of 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid, ethyl ester (568.22g), add entry (1L), then under the ice bath cooling, drip 4N aqueous sodium hydroxide solution (500ml).At room temperature stirred 3 days.Reaction mixture is splashed in 3N hydrochloric acid (1.2L) under the ice bath cooling.In the suspension that obtains, add entry (2L), after at room temperature stirring, leach the solid of separating out, under reduced pressure under 110 ℃, carry out drying, obtain white crystals title compound (504.71g).
(operation 6) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzo
Triazol-1-yl)-preparation of ester;
At the N of 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4.88g), in dinethylformamide (70ml) solution, add I-hydroxybenzotriazole-hydrate (2.73g), then add EDC hydrochloride (3.42g).At room temperature stirred 24 hours, then in reaction solution with adding entry 120ml in about 2 hours several times.Leach the solid of separating out, obtain yellow solid title compound (5.84g).
H NMR(400MHz，DMSO-d
6)
δ：13.52(3H，br s)，11.25(2H，s)，8.01-7.82(4H，m)，7.75-7.71(1H，m)，7.60-7.54(1H，m)，7.45-7.41(1H，m)，7.04(1H，s).
(operation 7) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid
The preparation of imidazolide;
1, in tetrahydrofuran (THF) (1.3L) suspension of 1 '-carbonyl dimidazoles (64.65g) at tetrahydrofuran (THF) (700ml) solution of 55 ℃ of following Dropwise 5s-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (100.05g).After stirring 1 hour under 73 ℃, in reaction mixture, add vinyl acetic monomer (500ml), under reduced pressure concentrate.In residue, add in the suspension of vinyl acetic monomer (1L) and hexane (2L) formation, under the ice bath cooling, add cold water (1L) and also stirred 10 minutes.Leach the solid of separating out, obtain white crystal title compound (110.42g).
1H NMR(400MHz，DMSO-d
6)
δ：13.97(1H，br s)，11.66(1H，br s)，8.76(1H，s)，8.05-7.87(3H，m)，7.18(1H，s)，6.90(1H，s).
The preparation of reference example 2:3-amino methyl-2-isopropoxy-pyridine
The preparation of (operation 1) 2-isopropoxy-niacinamide
In 2-propyl alcohol (45ml) solution of 2-chloro-nicotinamide (1.50g), add 60% sodium hydride (640mg).Stirred 2 days down at 100 ℃, then reaction solution is injected water (50ml), (80ml) extracts with vinyl acetic monomer.Organic layer is washed with 1N hydrochloric acid, carry out drying with anhydrous sodium sulphate after, concentrate.The residue that obtains is made with extra care with silica gel column chromatography (hexane-vinyl acetic monomer, 5: 1 → 2: 1), obtained clear crystal title compound (1.64g).
The preparation of (operation 2) 2-isopropoxy-cigarette nitrile (nicotinonitrile)
In chloroform (16ml) solution of 2-isopropoxy-niacinamide (1.64g), add triethylamine (2.8ml), then under the ice bath cooling, drip trichoroacetic chloride (1.1ml).After at room temperature stirring a night, in reaction solution, add saturated sodium bicarbonate aqueous solution and stirred 30 minutes.Organic layer is washed with saturated aqueous common salt, carry out drying with anhydrous sodium sulphate after, under reduced pressure concentrate, obtain brown oil title compound (1.37g).
The preparation of (operation 3) 3-amino methyl-2-isopropoxy-pyridine
In methyl alcohol (25ml) solution of 2-isopropoxy-cigarette nitrile (1.37g), add concentrated hydrochloric acid (2.1ml) and 7.5% palladium-carbon (780mg), under hydrogen atmosphere, at room temperature stirred 18 hours.Leach catalyzer, then filtrate is under reduced pressure concentrated the oily matter that obtains and be dissolved in water, wash with vinyl acetic monomer.After making water layer be alkalescence, extract with chloroform.It is refining with silica gel column chromatography (chloroform-methanol, 8: 1) organic layer to be concentrated the residue that obtains, and obtains brown oil title compound (545mg).
Below, according to above-mentioned preparation method A-1, prepare following compound.
[embodiment 1-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl first
Base)-preparation of acid amides
5-(the 2-chloro-4 that obtains in operation 7 by reference example 1; 5-two fluoro-benzoyl-amidos)-N of 1H-pyrazoles-3-carboxylic acid imidazolide (6.00g); in dinethylformamide (50ml) suspension, under the ice bath cooling, add 3-picolyl amine (1.72ml).At room temperature stir a night, in reaction mixture, add the aqueous solution (25ml), saturated sodium bicarbonate aqueous solution (50ml) then.Leach the solid of separating out, obtain white solid title compound (4.49g).
[embodiment 1-1-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl first
Base)-preparation of acid amides dihydrochloride
In methyl alcohol (10ml) suspension of the 5-that obtains by embodiment 1-1 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides (1.05g), add 4N hydrochloric acid-vinyl acetic monomer (1.8ml).It is about 5ml that reaction mixture is under reduced pressure concentrated up to residue, leaches the solid of separating out then, obtains white crystals title compound (1.13g).
[embodiment 1-1-2]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl first
Base)-preparation of amide hydrochloride
In methyl alcohol (15ml) suspension of the 5-that obtains by embodiment 1-1 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides (700mg), add 4N hydrochloric acid-vinyl acetic monomer (1.5ml).Reaction mixture is under reduced pressure concentrated, in residue, add methyl alcohol (7.5ml), stirred 8 hours down at 80 ℃.After being cooled to room temperature, leach solid, obtain white crystals title compound (638mg).
[embodiment 1-2]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles
-5-ylmethyl)-preparation of acid amides
The preparation of (operation 1) 5-chloromethyl-4-methyl- azoles;
In chloroform (10ml) solution of 5-hydroxymethyl-4-methyl- azoles (1.01g), add triethylamine (1.4ml).In this solution, under the ice bath cooling, add methylsulfonyl chloride (0.83ml), at room temperature stir a night.In reaction solution, add saturated sodium bicarbonate aqueous solution, stir after 30 minutes, separate organic layer.With organic layer saturated common salt water washing, use anhydrous sodium sulfate drying, under reduced pressure concentrate then, obtain brown oil title compound (955mg).
The preparation of (operation 2) 5-amino methyl-4-methyl- azoles;
In two alkane (20ml) solution of 5-chloromethyl-4-methyl- azoles (955mg), add 28% ammoniacal liquor (100ml), at room temperature stir a night.Reaction mixture is under reduced pressure concentrated, add 8N potassium hydroxide aqueous solution (20ml), with tetrahydrofuran (THF) (20ml) extraction organism.With the organic layer anhydrous sodium sulfate drying, under reduced pressure concentrate then, obtain brown oil title compound (502mg).
(reference Synth.Commun., 22 (13), 1939-1948,1992.)
(operation 3) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-first
Base- azoles-5-ylmethyl)-preparation of acid amides
5-(the 2-chloro-4 that obtains in operation 7 by reference example 1; 5-two fluoro-benzoyl-amidos)-N of 1H-pyrazoles-3-carboxylic acid imidazolide (2.00g); add 5-amino methyl-4-methyl- azoles (502mg) in dinethylformamide (6ml) suspension, at room temperature stir a night.In reaction mixture, add saturated sodium bicarbonate aqueous solution (30ml), then add entry (30ml).Leach the solid of separating out, obtain white solid title compound (1.11g).
[embodiment 1-2-1a]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles
-5-ylmethyl)-preparation of acid amides 3/2 hydrochloride
In methyl alcohol (2ml) suspension of the 5-that obtains by embodiment 1-2 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides (200mg), add 4N hydrochloric acid-vinyl acetic monomer (0.15ml).In reaction mixture, add vinyl acetic monomer, leach the solid of separating out, obtain white solid title compound (53mg).
[embodiment 1-2-1b]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles
-5-ylmethyl)-preparation of acid amides tosilate
Ethanol (1.9ml) solution that in acetone (8ml) solution of 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides (828mg), under 55 ℃, add tosic acid-hydrate salt (380mg).After 2 hours, reaction solution is cooled to room temperature and stirred 2 hours, leach the crystallization of separating out, obtain white solid title compound (1.052g).
[embodiment 1-2-1c]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles
-5-ylmethyl)-preparation of acid amides L-(+)-tartrate
At 5-(2-chloro-4; 5-two fluoro-benzoyl-amidos)-and add L-(+)-tartrate (45mg) in acetone (1.1ml) solution of 1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides (100mg), this reaction mixture was at room temperature stirred one day.Leach the solid of separating out, obtain white solid title compound (70mg).
[embodiment 1-2-2]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2, the 4-dimethyl-
azoles-5-ylmethyl)-preparation of acid amides tosilate
(operation 1) 2, the preparation of 4-dimethyl- azoles-5-carboxylic acid, ethyl ester;
In 2-chloroacetyl acetacetic ester (22.91g), add ethanamide (17.01g), stirred 28 hours down at 120 ℃.In reaction mixture, add entry (75ml) and ethanol (7.5ml), after the ice bath cooling, leach the solid of separating out, obtain brown solid title compound (10.82g).
(operation 2) 2, the preparation of 4-dimethyl-5-hydroxymethyl- azoles;
In tetrahydrofuran (THF) (30ml) suspension of lithium aluminum hydride (1.82g), under the ice bath cooling, drip 2, tetrahydrofuran (THF) (30ml) solution of 4-dimethyl- azoles-5-carboxylic acid, ethyl ester (7.845g).Stir after 1 hour 30 minutes, in reaction mixture, add entry (1.8ml), 15% aqueous sodium hydroxide solution (1.8ml), water (5.4ml) successively, at room temperature stir.Behind anhydrous sodium sulfate drying, under reduced pressure concentrate, obtain yellow oily title compound (5.539g).
(operation 3) 5-chloromethyl-2, the preparation of 4-dimethyl- triazole hydrochloride;
2, in chloroform (50ml) solution of 4-dimethyl-5-hydroxymethyl- azoles (5.539g), under the ice bath cooling, thionyl chloride (4.2ml).At room temperature stirred 3 hours, and then reaction mixture was under reduced pressure concentrated, obtain brown solid title compound (6.626g).
(operation 4) 5-azido methyl-2, the preparation of 4-dimethyl- azoles;
At 5-chloromethyl-2, the N of 4-dimethyl- triazole hydrochloride (6.626g) adds triethylamine (6ml) in dinethylformamide (18ml) solution, then adds the 20% Lithium Azide aqueous solution (10ml), stirs 6 hours down at 60 ℃.Add vinyl acetic monomer (100ml) in reaction mixture, water, saturated aqueous common salt wash successively, carry out drying with anhydrous sodium sulphate, under reduced pressure concentrate then, obtain brown oil title compound (4.31g).
(operation 5) 5-amino methyl-2, the preparation of 4-dimethyl- azoles dihydrochloride;
At 5-azido methyl-2, in tetrahydrofuran (THF) (45ml) solution of 4-dimethyl- azoles (4.31g),, then add entry (1.2ml) at 50 ℃ of tetrahydrofuran (THF) (25ml) solution that add triphenylphosphine (8.27g) down, stir whole night.Reaction mixture is under reduced pressure concentrated, in residue, add diethyl ether (50ml) then, leach the solid of separating out.After filtrate under reduced pressure concentrated, be dissolved in the vinyl acetic monomer (20ml), will add the solid that 4N hydrochloric acid-vinyl acetic monomer (15ml) separates out and leach acquisition yellow solid title compound (5.30g).
(operation 6) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4
-dimethyl- azoles-5-ylmethyl)-preparation of acid amides
At 5-amino methyl-2; the N of 4-dimethyl- azoles dihydrochloride (772mg); in dinethylformamide (3ml) solution; under the ice bath cooling; 5-(the 2-chloro-4 that adds triethylamine (1.14ml) and obtain by the operation 7 of reference example 1; 5-two fluoro-benzoyl-amidos)-and 1H-pyrazoles-3-carboxylic acid imidazolide (1.37g), at room temperature stir a night.In reaction mixture, add entry (24ml), leach the solid of separating out, obtain white solid title compound (1.47g).
(operation 7) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4
-dimethyl- azoles-5-ylmethyl)-preparation of acid amides tosilate
In 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides (1.00g), add 1-propyl alcohol (6ml), carry out reflux.In this solution, add 1-propyl alcohol (0.5ml) solution of tosic acid-hydrate (466mg), under refluxing, stirred 30 minutes, be cooled to room temperature then and stir a night.Leach the crystal of separating out, obtain colourless crystallization title compound (1.36g).
[embodiment 1-3]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2, the 4-dimethyl-
The pyridin-3-yl methyl)-preparation of acid amides
(operation 1) 3-carboxyl methyl-2, the preparation of 4-lutidine;
2, in tetrahydrofuran (THF) (30ml) solution of 4-lutidine-3-carboxylic acid, ethyl ester (3.00g), under the ice bath cooling, slowly add lithium aluminum hydride (1.21g).Stir after 2 hours, in reaction mixture, add entry (1.2ml), 15% aqueous sodium hydroxide solution (1.2ml), water (3.6ml) successively, at room temperature stir.Tell organic layer, behind anhydrous sodium sulfate drying, under reduced pressure concentrate, obtain white crystals title compound (2.26g).
(operation 2) 3-chloromethyl-2, the preparation of 4-lutidine;
At 3-hydroxymethyl-2, in chloroform (30ml) solution of 4-lutidine (3.00g), under the ice bath cooling, thionyl chloride (2.8ml).At room temperature stirred 1 hour 30 minutes, and in reaction mixture, under the ice bath cooling, added saturated sodium bicarbonate aqueous solution (60ml) then.Organic layer is washed with saturated aqueous common salt, use anhydrous sodium sulfate drying, under reduced pressure concentrate then, obtain brown oil title compound (3.45g).
(operation 3) 3-azido methyl-2, the preparation of 4-lutidine;
At 3-chloromethyl-2, the N of 4-lutidine (3.45g) in dinethylformamide (15ml) solution, adds the 20% Lithium Azide aqueous solution (5.5ml), stirs a night down at 60 ℃.Add vinyl acetic monomer (100ml) in reaction mixture, water, saturated aqueous common salt wash successively, use anhydrous sodium sulfate drying, under reduced pressure concentrate then, obtain brown oil title compound (3.18g).
(operation 4) 3-amino methyl-2, the preparation of 4-lutidine;
At 3-azido methyl-2, add platinum oxide-carbon (613mg) in ethanol (45ml) solution of 4-lutidine (3.18g), under 4 atmospheric hydrogen atmosphere gases, at room temperature stirred 30 minutes.Leach catalyzer, then filtrate is under reduced pressure concentrated, obtain brown oil title compound (2.53g).
(operation 5) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4
-dimethyl-pyridin-3-yl methyl)-preparation of acid amides
At 3-amino methyl-2; the N of 4-lutidine (2.53g) in dinethylformamide (15ml) solution, adds 5-(the 2-chloro-4 that the operation 7 by reference example 1 obtains; 5-two fluoro-benzoyl-amidos)-and 1H-pyrazoles-3-carboxylic acid imidazolide (6.21g), at room temperature stir a night.In reaction mixture, add entry (50ml), then add 10% potassium hydroxide aqueous solution (15ml), leach the solid of separating out, obtain white solid title compound (7.02g).
[embodiment 1-3-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2, the 4-dimethyl-
The pyridin-3-yl methyl)-preparation of acid amides dihydrochloride
In methyl alcohol (1ml) solution of the 5-that obtains by embodiment 1-3 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-acid amides (120mg), add 4N hydrochloric acid-vinyl acetic monomer (0.2ml).In reaction mixture, add vinyl acetic monomer, leach the solid of separating out, obtain white solid title compound (135mg).
Prepare the compound of embodiment 1-4 to embodiment 1-167 in the same manner with the foregoing description 1-1 to embodiment 1-3-1.The structural formula of these compounds and NMR data are shown in following table 1-24.
Table 1
Table 2
Table 3
Table 4
Table 5
Table 6
Table 7
Table 8
Table 9
Table 10
Table 11
Table 12
Table 13
Table 14
Table 15
Table 16
Table 17
Table 18
Table 19
Table 20
Table 21
Table 22
Table 23
Table 24
Below, according to above-mentioned preparation method A-2, the compound that preparation is following.
[embodiment 2-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridine-
The 3-ylmethyl)-preparation of acid amides
5-(the 2-chloro-4 that obtains in operation 6 by reference example; 5-two fluoro-benzoyl-amidos)-N of 1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (2.15g); in dinethylformamide (11ml) solution; add commercially available 3-amino methyl-6-chloro-pyridine (0.77g), at room temperature stirred 3 hours.In reaction mixture, drip water 10ml, leach the solid of separating out then, obtain title compound (2.10g).
[embodiment 2-1-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridine-
The 3-ylmethyl)-preparation of acid amides dihydrochloride
In methyl alcohol (10ml)-tetrahydrofuran (THF) (10ml) solution of the 5-that obtains by embodiment 2-1 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides (1.16g), add 4N hydrochloric acid-vinyl acetic monomer solution (1.7ml) and leave standstill.Leach the solid of separating out, obtain title compound (1.07g).
[embodiment 2-2]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4]
Triazole-3-ylmethyl)-preparation of acid amides
With embodiment 2-1 in the same manner; by 5-(2-chloro-4; 5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (160mg) and according to document (Bioorganic Med.Chem.Lett.; 4; 2441; 1994.) preparation (4H-[1,2,4] triazole-3-ylmethyl)-amine (42mg) acquisition title compound (50mg).
[embodiment 2-2-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4]
Triazole-3-ylmethyl)-preparation of acid amides dihydrochloride
With embodiment 2-1-1 in the same manner, obtain title compound (30mg) by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides (37mg).
[embodiment 2-3]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinoline
Azoles quinoline-3-yl)-preparation of acid amides
With embodiment 2-1 in the same manner; by 5-(2-chloro-4; 5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (210mg) and according to document (J.HeterocyclicChem.; 12; 883 1975.) Zhi Bei 5-fluoro-3,4-dihydro-chinazoline (150mg) obtains title compound (155mg).
[embodiment 2-3-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinoline
Azoles quinoline-3-yl)-preparation of acid amides dihydrochloride
With embodiment 2-1-1 in the same manner, obtain title compound (23mg) by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides (48mg).
[embodiment 2-4]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4, the 6-dimethyl-
The pyridin-3-yl methyl)-preparation of acid amides
(operation 1) 3-amino methyl-4, the preparation of 6-dimethyl-pyridine;
According to document (Tetrahedron, 22,3417,1996.), by 2-chloro-3-cyano group-4,6-dimethyl-pyridine (2.00g) preparation 3-cyano group-4,6-dimethyl-pyridine (1.23g).
In addition, according to document (J.Heterocyclic Chem., 30,473,1993.), by 3-cyano group-4,6-dimethyl-pyridine prepares title compound (436mg).
(operation 2) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6
-dimethyl-pyridin-3-yl methyl)-preparation of acid amides
With embodiment 2-1 in the same manner; by 5-(2-chloro-4; 5-two fluoro-benzoyl-amidos)-and 1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (140mg) and the 3-amino methyl-4 that obtains by operation 1,6-dimethyl-pyridine (70mg) obtains title compound (110mg).
[embodiment 2-4-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4, the 6-dimethyl-
The pyridin-3-yl methyl)-preparation of acid amides dihydrochloride
At 5-(2-chloro-4; 5-two fluoro-benzoyl-amidos)-add 4N hydrochloric acid-vinyl acetic monomer solution (0.64ml) in methyl alcohol (0.5ml)-tetrahydrofuran (THF) (25ml) suspension of 1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides (430mg).The solution that obtains is under reduced pressure concentrated, behind the simmer down to about 1/6, leave standstill, and leach the solid of separating out, obtain title compound (444mg).
[embodiment 2-5]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6
-methyl-pyridin-3-yl methyl)-preparation of acid amides
The preparation of (operation 1) 3-amino methyl-2-methoxyl group-6-methyl-pyridine;
According to document (J.Heterocyclic Chem., 36,653,1999.), by 2-chloro-3-cyano group-6-picoline (3.00g) preparation 3-cyano group-2-methoxyl group-6-picoline (2.74g).In addition, according to document (J.Heterocyclic Chem., 30,473,1993.), by 3-cyano group-2-methoxyl group-6-picoline (739mg) preparation title compound (608mg).
(operation 2) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-first
Oxygen base-6-methyl-pyridin-3-yl methyl)-preparation of acid amides
With embodiment 2-1 in the same manner; obtain title compound (501mg) by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (1.66g) and 3-amino methyl-2-methoxyl group of obtaining by operation 1-6-methyl-pyridine (603mg).
[embodiment 2-6]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6
-methyl-pyridin-3-yl methyl)-preparation of acid amides
The preparation of (operation 1) 4-methoxyl group-6-methylnicotinic acid ethyl ester;
According to document (Synthesis, 6,479,1988.), by 2,4-two chloro-6-methylnicotinic acid ethyl esters (1.00g) preparation 2-chloro-4-methoxyl group-6-methylnicotinic acid ethyl ester (387mg), again according to the document, preparation title compound (217mg).
The preparation of (operation 2) 3-hydroxymethyl-4-methoxyl group-6-picoline;
According to document (Synthesis, 26,2257,1996.), by 4-methoxyl group-6-methylnicotinic acid ethyl ester (212mg) preparation title compound (61mg).
The preparation of (operation 3) 3-amino methyl-4-methoxyl group-6-methyl-pyridine;
According to document (J.Med.Chem., 46,453,2003.), by 3-hydroxymethyl-4-methoxyl group-6-picoline (553mg) preparation 3-chloromethyl-4-methoxyl group-6-picoline.It is not made with extra care,, form 3-azido methyl-4-methoxyl group-6-picoline (403mg) with reaction of sodium azide, and then according to the document, preparation title compound (331mg).
(operation 4) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-first
Oxygen base-6-methyl-pyridin-3-yl methyl)-preparation of acid amides
With embodiment 2-1 in the same manner; obtain title compound (368mg) by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (413mg) and 3-amino methyl-4-methoxyl group of obtaining by operation 3-6-methyl-pyridine (150mg).
[embodiment 2-6-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6
-methyl-pyridin-3-yl methyl)-preparation of acid amides dihydrochloride
With embodiment 2-4-1 in the same manner, by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides (363mg) preparation title compound (124mg).
[embodiment 2-7]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,
6-dimethyl-pyridin-3-yl methyl)-preparation of acid amides
(operation 1) 3-amino methyl-2-methoxyl group-4, the preparation of 6-dimethyl-pyridine;
According to document (J.Heterocyclic Chem., 36,653,1999.), by 3-cyano group-2-chloro-4,6-lutidine (1.50g) preparation 3-cyano group-2-methoxyl group-4,6-lutidine (1.31g).In addition, according to document (J.Heterocyclic Chem., 30,473,1993.), by 3-cyano group-2-methoxyl group-4,6-lutidine (809mg) preparation title compound (826mg).
(operation 2) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-first
Oxygen base-4,6-dimethyl-pyridin-3-yl methyl)-preparation of acid amides
With embodiment 2-1 in the same manner, by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzotriazole-1-yl)-ester (1.26g) and the 3-amino that obtains by operation 1
Methyl-2-methoxyl group-4,6-dimethyl-pyridine (500mg) obtains title compound (1.23g).
[embodiment 2-7-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,
6-dimethyl-pyridin-3-yl methyl)-preparation of acid amides dihydrochloride
With embodiment 2-1-1 in the same manner, by 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides (261mg) preparation title compound (288mg).
With the foregoing description 2-1 to embodiment 2-7-1 in the same manner, the compound of embodiment 2-8 to the embodiment 2-33 of preparation shown in the following table.
Table 25
Table 26
Table 27
Table 28
Table 29
Table 30
According to above-mentioned preparation method A-3, prepare following compound.
[embodiment 3-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzyl-methyl-acyl
The preparation of amine;
5-(the 2-chloro-4 for preparing in operation 5 according to reference example 1; 5-two fluoro-benzoyl-amidos)-N of 1H-pyrazoles-3-carboxylic acid (70mg), N-methylbenzylamine (0.033ml) and I-hydroxybenzotriazole-hydrate (43mg); in dinethylformamide (1ml) solution; add EDC hydrochloride (50mg), at room temperature stir a night.In reaction mixture, add saturated sodium bicarbonate aqueous solution (2ml), then add entry (5ml), leach the solid of separating out, obtain white solid title compound (76mg).
[embodiment 3-2]
The system of 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide
Be equipped with;
5-(the 2-chloro-4 for preparing in operation 5 according to reference example 1; 5-two fluoro-benzoyl-amidos)-N of 1H-pyrazoles-3-carboxylic acid (70mg), benzylamine (0.028ml) and I-hydroxybenzotriazole-hydrate (43mg); in dinethylformamide (1ml) solution; add EDC hydrochloride (50mg), at room temperature stir a night.In reaction mixture, add 0.1N aqueous sodium hydroxide solution (1ml), then add entry (3ml), leach the solid of separating out, obtain white solid title compound (66mg).
With the foregoing description 3-1 to embodiment 3-2 in the same manner, prepare the compound of following embodiment 3-3 to embodiment 3-53.
Table 31
Table 32
Table 33
Table 34
Table 35
Table 36
Table 37
According to above-mentioned preparation method B, prepare following compound.
[embodiment 4-1]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl
-phenyl)-preparation of methyl-acid amides;
(operation 1) 4-[methyl-(5-nitro-1H-pyrazoles-3-carbonyl) amino]-the benzene first
The preparation of acid methyl esters;
In chloroform (10ml) solution of 5-nitro-3-pyrazole carboxylic acid (400mg), under the ice bath cooling, add oxalyl chloride (0.27ml) and N, dinethylformamide (1).At room temperature stir a night, then reaction solution is under reduced pressure concentrated, obtain 5-nitro-3-pyrazolecarboxylic acid chlorides.
Then, in chloroform (25ml) suspension of 5-nitro-3-pyrazolecarboxylic acid chlorides and 4-methylamino methyl benzoate (410mg), add triethylamine (1.2ml), at room temperature stir a night.Reaction mixture is washed with saturated sodium bicarbonate aqueous solution, 1N hydrochloric acid, salt solution successively, use anhydrous sodium sulfate drying, under reduced pressure concentrate then.The residue that obtains is made with extra care with silica gel column chromatography (chloroform-vinyl acetic monomer, 5: 1 → 3: 1 → 2: 1), obtained white crystals title compound (394mg).
(operation 2) 4-[(5-amino-1H-pyrazoles-3-carbonyl)-methyl-amino]-benzene
The preparation of methyl-formiate;
At 4-[methyl-(5-nitro-1H-pyrazoles-3-carbonyl) amino]-tetrahydrofuran (THF) (10ml)-vinyl acetic monomer (10ml) solution of methyl benzoate (394mg) in, add 7.5% palladium-carbon (60mg), under hydrogen atmosphere gas, at room temperature stir a night.From reaction mixture, leach catalyzer, then filtrate is under reduced pressure concentrated, obtain white solid title compound (244mg).
(operation 3) 5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-
Methoxycarbonyl-phenyl)-preparation of methyl-acid amides;
At 4-[(5-amino-1H-pyrazoles-3-carbonyl)-methyl-amino]-add pyridine (0.1ml) in tetrahydrofuran (THF) (5ml) solution of methyl benzoate (244mg), under the ice bath cooling, the 2-chloro-4 that dropping is obtained by the operation 1 of reference example 1,5-difluoro benzoyl chloride (0.135ml).At room temperature stir a night, then reaction mixture is under reduced pressure concentrated, the residue that obtains is made with extra care with silica gel column chromatography (chloroform-vinyl acetic monomer, 5: 1 → 1: 1), obtain white crystals title compound (228mg).
[embodiment 4-2]
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)
The preparation of-methyl-acid amides;
At the 5-for preparing according to embodiment 4-1 (2-chloro-4; 5-two fluoro-benzoyl-amidos)-methyl alcohol (2ml) solution of 1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides (100mg) in; add 1N aqueous sodium hydroxide solution (0.7ml), at room temperature stir a night.In reaction mixture, add 1N hydrochloric acid (1.5ml), leach the solid of separating out, obtain white solid title compound (78mg).
[embodiment 4-2-1]
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-
Amino }-preparation of phenylformic acid sodium salt;
In ethanol (0.81ml) suspension of the 5-for preparing by embodiment 4-2 (2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides (49.4mg), add 4N aqueous sodium hydroxide solution (0.025ml).The solution that obtains is at room temperature left standstill, leach the solid of separating out, obtain title compound (36mg).
With the foregoing description 4-1 to embodiment 4-2-1 in the same manner, the compound of embodiment 4-3 to the embodiment 4-48 of preparation shown in the following table.
Table 38
Table 39
Table 40
Table 41
Table 42
Table 43
Table 44
Table 45
With above-mentioned preparation method A, B, C or above-mentioned each embodiment in the same manner, the compound of embodiment 5-1 to the embodiment 5-44 of preparation shown in the following table.
Table 46
Table 47
Table 48
Table 49
Table 50
Table 51
Table 52
Table 53
Similarly, the compound of embodiment 6-1 to the embodiment 6-50 shown in the preparation following table and the compound of embodiment 7-1 to embodiment 7-17.
Table 54
Table 55
Table 56
Table 57
Table 58
Table 59
Table 60
Table 61
Table 62
Table 63
Table 64
[pharmacological testing]
1. the active measuring method of test example (1) liver glycogen phosphorylase
The active measurement of glycogen phosphorylase is that the method for using the forward reaction system is carried out.
Using the active measurement of glycogen phosphorylase of forward reaction system carries out in accordance with the following methods.Utilize glycogen phosphorylase, to use phosphoglucomutase (phosphoglucomutase) and G-6-P ester desaturase [glucose-6-phosphate dehydrogenase (G6PDH)] to carry out transphosphorylation reaction, dehydrogenation reaction by glycogenetic glucose-1-phosphate (Glucose-1-phosphate), be converted to glucopyrone 6-phosphoric acid ester (glucono-δ-lactone 6-phosphate).At this moment, in the dehydrogenation reaction of G6PDH, detect the NADPH that generates by NADP.
As the enzyme solution of human liver glycogen phosphorylase, used forced expression the cell homogenates of the Sf9 cell of recombinant human liver glycogen phosphorylase to dilute the solution that forms with 100mmol/L BES damping fluid (pH6.8 contains 2mmol/L EDTA).As matrix liquid, use phosphoric acid buffer (to contain 16mmol/L KH
2PO
4, 24mmol/L Na
2HPO
4).Use the BES damping fluid to modulate 8U/mL phosphoglucomutase (phosphoglucomutase), 60U/mL G6PDH mixed solution.The modulation reaction (contains 1.4mmol/L NADP, 30mmol/L MgCl with damping fluid respectively
2, 8 μ mol/L glucose-1, the 6-bisphosphate, the 8mg/mL glycogen, 40mmol/L BES, 0.8mmol/LEDTA) and glucose solution (contain 75mmol/L glucose, 100mmol/L BES, 2mmol/LEDTA).Detected material is dissolved in the 1%DMSO aqueous solution.
By in glucose solution 20 μ L, matrix liquid 20 μ L, the mixed solution of reaction, add recombinant human liver glycogen phosphorylase solution 20 μ L and phosphoglucomutase (phosphoglucomutase), G6PDH mixed solution 20 μ L and begin enzymatic reaction with damping fluid 100 μ L, detected material 20 μ L.In contrast, add the 1%DMSO aqueous solution and replace detected material.The solution that does not add matrix as blank.After the reaction beginning, measure the absorbancy under the 340nm at once.After at room temperature reacting 75 minutes, measure the absorbancy under the 340nm once more.Enzymic activity is the value that is deducted the absorbancy variable quantity gained in the barren 75 minutes by the absorbancy variable quantity in 75 minutes.
2. the measuring method of test example (2) plasma glucose concentration
Use is as the db/db mouse of obese diabetic model, and research The compounds of this invention (1) is to the influence of glucose concn in the blood plasma.Measure glucose concn in the db/db mouse blood plasma in (9-18 age in week), do not have the mode of difference, mouse is divided into 5 every group or 8 according to the mean value of glucose concn in each group blood plasma.After going on a hunger strike 4 hours,, measure administration glucose concn in the blood plasma after 1 hour and 3 hours to db/db mouse oral administration embodiment compound or solvent (0.5% methylcellulose gum).The evaluation of the blood sugar reduction effect of embodiment compound is according to per hour giving group of solvents and giving have heterodyne to test between the embodiment compound group to carry out (Dunnett detection).
The biologically active data of embodiment compound is shown in following table 65-79.
The inhibiting rate of detected material (%) is to calculate according to " (1-(enzymic activity of detected material)/(enzymic activity of contrast)) * 100 ".
IC
50Value is after calculating linear equation according to the concentration point that is positioned at inhibiting rate 50% front and back, and the concentration that is obtained by the intersection point with inhibiting rate 50% is calculated.
" IC
50" be the parameter of expression for the enzyme inhibition activity of liver glycogen phosphorylase, IC
50Be lower than the usefulness of 100nmol/L ++ expression, the usefulness that 100nmol/L is above, be lower than 300nmol/L+represent.Work as IC
50Be 300nmol/L when above, the invention compound under finite concentration (nmol) inhibiting rate (%) as shown in Table.For example, if be 20% inhibiting rate under 300nmol/L, then be expressed as 20% (300).
In addition, " vivo " expression is for the blood sugar reduction effect of db/db mouse, to demonstrate the compound of significant blood sugar reduction effect on the statistics with the consumption below the 10mg/kg, with ++ expression, but nonsensical consumption with 10mg/kg on the statistics is demonstrated the compound of tangible blood sugar reduction effect, with+represent.
Table 65
| Example | IC 50 | vivo |
| 1-1 | ++ | |
| 1-1-1 | ++ | ++ |
| 1-1-2 | ++ | |
| 1-2 | ++ | ++ |
| 1-2-1a | ++ | ++ |
| 1-2-2 | ++ | |
| 1-3-1 | ++ | ++ |
| 1-4 | ++ | |
| 1-5 | ++ | |
| 1-6 | + | |
| 1-7 | + | |
| 1-8 | ++ | |
| 1-9 | ++ | |
| 1-10 | + | |
| 1-11 | + | |
| 1-12 | ++ | ++ |
| 1-13 | ++ | |
| 1-14 | ++ | |
| 1-15 | ++ | + |
| 1-16 | ++ | |
| 1-17 | ++ | |
| 1-18 | ++ | + |
| 1-19 | ++ | + |
| 1-20 | ++ | |
| 1-21 | ++ | + |
| 1-22 | ++ | |
| 1-23 | ++ | |
| 1-24 | ++ | + |
| 1-25 | ++ | + |
| 1-26 | ++ | + |
| 1-27 | ++ | |
| 1-28 | ++ | |
| 1-29 | ++ | |
| 1-30 | ++ | |
| 1-31 | ++ | + |
| 1-32 | ++ | |
| 1-33 | ++ | |
| 1-34 | ++ | |
| 1-35 | ++ |
Table 66
| Example | IC 50 | vivo |
| 1-36 | ++ | |
| 1-37 | ++ | + |
| 1-38 | ++ | + |
| 1-39 | ++ | + |
| 1-40 | ++ | + |
| 1-41 | ++ | + |
| 1-42 | ++ | + |
| 1-43 | ++ | |
| 1-44 | ++ | |
| 1-45 | ++ | |
| 1-46 | ++ | ++ |
| 1-47 | ++ | |
| 1-48 | ++ | |
| 1-49 | ++ | |
| 1-50 | ++ | + |
| 1-51 | ++ | |
| 1-52 | ++ | + |
| 1-53 | ++ | |
| 1-54 | ++ | |
| 1-55 | ++ | |
| 1-56 | ++ | + |
| 1-57 | ++ | |
| 1-58 | ++ | |
| 1-59 | ++ | ++ |
| 1-60 | ++ | |
| 1-61 | ++ | |
| 1-62 | ++ | |
| 1-63 | ++ | + |
| 1-64 | ++ | ++ |
| 1-65 | ++ | |
| 1-66 | ++ | + |
| 1-67 | ++ | + |
| 1-68 | ++ | + |
| 1-69 | ++ | + |
| 1-70 | ++ | ++ |
| 1-71 | ++ | + |
| 1-72 | ++ | + |
| 1-73 | ++ | + |
| 1-74 | + | |
| 1-75 | ++ |
Table 67
| Example | IC 50 | vivo |
| 1-76 | ++ | |
| 1-77 | 43.8％(1000) | |
| 1-78 | ++ | + |
| 1-79 | 23.3％(300) | |
| 1-80 | ++ | + |
| 1-81 | ++ | + |
| 1-82 | ++ | + |
| 1-83 | 6.1％(300) | |
| 1-84 | ++ | ++ |
| 1-85 | ++ | |
| 1-86 | 17.0％(300) | |
| 1-87 | ++ | + |
| 1-88 | ++ | + |
| 1-89 | ++ | |
| 1-90 | ++ | + |
| 1-91 | ++ | + |
| 1-92 | 11.7％(300) | |
| 1-93 | ++ | |
| 1-94 | 36.5％(300) | |
| 1-95 | ++ | + |
| 1-96 | ++ | + |
| 1-97 | ++ | |
| 1-98 | ++ | + |
| 1-99 | ++ | + |
| 1-100 | ++ | + |
| 1-101 | ++ | |
| 1-102 | ++ | |
| 1-103 | 21.6％(300) | |
| 1-104 | 32.3％(300) | |
| 1-105 | + | |
| 1-106 | + | |
| 1-107 | ++ | ++ |
| 1-108 | 45.3％(300) | |
| 1-109 | 33.3％(300) | |
| 1-110 | ++ | |
| 1-111 | + | |
| 1-112 | 49.9％(300) | |
| 1-113 | ++ | ++ |
| 1-114 | 38.9％(300) | |
| 1-115 | 39.7％(300) |
Table 68
| Example | IC 50 | vivo |
| 1-116 | ++ | ++ |
| 1-117 | ++ | + |
| 1-118 | ++ | |
| 1-119 | + | |
| 1-120 | ++ | |
| 1-121 | ++ | |
| 1-122 | ++ | |
| 1-123 | ++ | + |
| 1-124 | ++ | |
| 1-125 | ++ | |
| 1-126 | ++ | + |
| 1-127 | ++ | + |
| 1-128 | ++ | + |
| 1-129 | ++ | + |
| 1-130 | ++ | + |
| 1-131 | ++ | |
| 1-132 | ++ | |
| 1-133 | ++ | + |
| 1-134 | ++ | + |
| 1-135 | ++ | + |
| 1-136 | ++ | + |
| 1-137 | ++ | + |
| 1-138 | ++ | + |
| 1-139 | 22.9％(100) | |
| 1-140 | 30.8％(100) | |
| 1-141 | 31.4％(100) | |
| 1-142 | ++ | |
| 1-143 | ++ | |
| 1-144 | 5％(100) | |
| 1-145 | 12.8％(100) | |
| 1-146 | 11.3％(100) | |
| 1-147 | 9.6％(100) | |
| 1-148 | 14.1％(100) | |
| 1-149 | 20.8％(100) | |
| 1-150 | 13.8％(100) | |
| 1-151 | 13.3％(100) | |
| 1-152 | ++ | |
| 1-153 | ++ | |
| 1-154 | ++ | |
| 1-155 | ++ |
Table 69
| Example | IC 50 | vivo |
| 1-156 | ++ | |
| 1-157 | ++ | |
| 1-158 | ++ | |
| 1-159 | + | |
| 1-160 | ++ | |
| 1-161 | ++ | |
| 1-162 | ++ | |
| 1-163 | ++ | |
| 1-164 | ++ | |
| 1-165 | ++ | |
| 1-166 | ++ | |
| 1-167 | ++ |
Table 70
| Example | IC 50 | vivo |
| 2-1 | ++ | |
| 2-1-1 | ++ | + |
| 2-2-1 | ++ | |
| 2-3-1 | ++ | |
| 2-4-1 | ++ | ++ |
| 2-5 | ++ | ++ |
| 2-6 | ++ | ++ |
| 2-6-1 | ++ | ++ |
| 2-7-1 | ++ | ++ |
| 2-8 | ++ | + |
| 2-9 | ++ | + |
| 2-10 | ++ | + |
| 2-11 | ++ | + |
| 2-12 | ++ | ++ |
| 2-13 | ++ | + |
| 2-14 | 37.5％(300) | |
| 2-15 | ++ | + |
| 2-16 | ++ | |
| 2-17 | ++ | |
| 2-18 | ++ | |
| 2-19 | ++ | |
| 2-20 | 43.1％(100) | |
| 2-21 | 5.7％(100) | |
| 2-22 | ++ | |
| 2-23 | ++ | + |
| 2-24 | ++ | + |
| 2-25 | ++ | + |
| 2-26 | 36.4％(100) | |
| 2-27 | ++ | + |
| 2-28 | ++ | + |
| 2-29 | 45.8％(100) | |
| 2-30 | 1.8％(100) | |
| 2-31 | 5.5％(100) | |
| 2-32 | ++ | |
| 2-33 | ++ |
Table 71
| Example | IC 50 | vivo |
| 3-1 | 50％(490) | |
| 3-2 | + | + |
| 3-3 | 50％(640) | |
| 3-4 | + | + |
| 3-5 | 41.1％(1000) | |
| 3-6 | 42.5％(1000) | |
| 3-8 | 11.7％(1000) | |
| 3-9 | 50％(480) | |
| 3-10 | 23.2％(1000) | |
| 3-11 | ++ | + |
| 3-12 | 50％(400) | |
| 3-13 | 25.5％(1000) | |
| 3-14 | 41.7％(1000) | |
| 3-15 | + | |
| 3-16 | ++ | |
| 3-17 | ++ | |
| 3-18 | + | |
| 3-19 | 9.2％(1000) | |
| 3-20 | ++ | + |
| 3-21 | ++ | ++ |
| 3-22 | 50％(640) | |
| 3-23 | 26.1％(1000) | |
| 3-24 | ++ | + |
| 3-25 | ++ | + |
| 3-26 | ++ | + |
| 3-27 | 41.5％(300) | |
| 3-28 | + | |
| 3-29 | ++ | + |
| 3-30 | ++ | |
| 3-31 | ++ | + |
| 3-32 | ++ | + |
| 3-33 | ++ | + |
| 3-34 | ++ | |
| 3-35 | ++ | ++ |
| 3-36 | ++ | |
| 3-37 | ++ | |
| 3-38 | ++ | + |
| 3-39 | ++ | + |
| 3-40 | ++ | ++ |
Table 72
| Example | IC 50 | vivo |
| 3-41 | ++ | ++ |
| 3-42 | 1.1％(300) | |
| 3-43 | 13.4％(300) | |
| 3-44 | + | |
| 3-45 | ++ | + |
| 3-46 | ++ | + |
| 3-47 | ++ | |
| 3-48 | ++ | |
| 3-49 | ++ | |
| 3-50 | ++ | |
| 3-51 | ++ | |
| 3-52 | ++ | |
| 3-53 | ++ |
Table 73
| Example | IC 50 | vivo |
| 4-1 | 13.8％(1000) | |
| 4-2 | ++ | ++ |
| 4-2-1 | ++ | ++ |
| 4-3 | + | |
| 4-4 | ++ | + |
| 4-5 | + | |
| 4-6 | + | |
| 4-7 | + | |
| 4-8 | + | |
| 4-9 | ++ | + |
| 4-10 | 50％(590) | |
| 4-11 | ++ | |
| 4-12 | + | |
| 4-13 | 38.0％(300) | |
| 4-14 | 10.6％(300) | |
| 4-15 | + | |
| 4-16 | 5.1％(300) | |
| 4-17 | 1.1％(300) | |
| 4-18 | ++ | + |
| 4-19 | 3.3％(300) | |
| 4-20 | 3.3％(300) | |
| 4-21 | 24.2％(300) | |
| 4-23 | ++ | + |
| 4-24 | + | |
| 4-25 | ++ | |
| 4-26 | ++ | |
| 4-27 | + | |
| 4-28 | + | |
| 4-32 | 7.8％(300) | |
| 4-33 | 15.2％(300) | |
| 4-34 | ++ | + |
| 4-35 | 9.7％(300) | |
| 4-39 | 5.3％(300) | |
| 4-40 | 3.6％(300) | |
| 4-41 | ++ | + |
| 4-42 | 8.5％(300) | |
| 4-43 | 3.8％(300) | |
| 4-44 | 5.7％(100) |
Table 74
| Example | IC 50 | vivo |
| 4-45 | 5.9％(100) | |
| 4-46 | ++ | + |
| 4-47 | 1.2％(100) | |
| 4-48 | ++ | ++ |
Table 75
| Example | IC 50 | vivo |
| 5-1 | ++ | + |
| 5-2 | ++ | + |
| 5-3 | ++ | |
| 5-4 | ++ | |
| 5-5 | ++ | |
| 5-6 | ++ | |
| 5-7 | ++ | |
| 5-8 | ++ | + |
| 5-9 | ++ | + |
| 5-10 | ++ | + |
| 5-11 | ++ | |
| 5-12 | ++ | + |
| 5-13 | ++ | + |
| 5-14 | ++ | + |
| 5-15 | ++ | + |
| 5-16 | ++ | + |
| 5-17 | ++ | + |
| 5-18 | ++ | |
| 5-19 | ++ | |
| 5-20 | ++ | |
| 5-21 | ++ | |
| 5-22 | ++ | |
| 5-23 | ++ | ++ |
| 5-24 | ++ | ++ |
| 5-25 | ++ | ++ |
| 5-26 | ++ | |
| 5-27 | ++ | ++ |
| 5-28 | ++ | + |
| 5-29 | ++ | ++ |
| 5-30 | ++ | + |
| 5-31 | ++ | + |
| 5-32 | ++ | + |
| 5-33 | ++ | + |
| 5-34 | ++ |
Table 76
| Example | IC 50 | vivo |
| 5-35 | ++ | + |
| 5-36 | 17.8％(100) | |
| 5-37 | 22.3％(100) | |
| 5-38 | 15.2％(100) | |
| 5-39 | ++ | |
| 5-40 | ++ | |
| 5-41 | ++ | + |
| 5-42 | ++ | + |
| 5-43 | ++ | + |
| 5-44 | ++ | + |
Table 77
| Example | IC 50 | vivo |
| 6-1 | 15.5％(100) | |
| 6-2 | 12.3％(300) | |
| 6-3 | 9.7％(300) | |
| 6-4 | 46.8％(300) | |
| 6-5 | ++ | |
| 6-6 | ++ | |
| 6-7 | 12.9％(300) | |
| 6-8 | 11.7％(300) | |
| 6-9 | 5.5％(300) | |
| 6-10 | + | |
| 6-11 | 2.1％(100) | |
| 6-12 | ++ | + |
| 6-13 | 17.5％(100) | |
| 6-14 | 20.1％(100) | |
| 6-15 | ++ | |
| 6-16 | ++ | + |
| 6-17 | 9.8％(100) | + |
| 6-18 | 6.8％(100) | |
| 6-19 | ++ | |
| 6-20 | ++ | |
| 6-21 | ++ | ++ |
| 6-22 | ++ | + |
| 6-23 | ++ | + |
| 6-24 | ++ | |
| 6-25 | ++ | |
| 6-26 | ++ | |
| 6-27 | ++ | |
| 6-28 | ++ | |
| 6-29 | ++ | |
| 6-30 | ++ | |
| 6-31 | ++ | |
| 6-32 | ++ | |
| 6-33 | ++ | + |
| 6-34 | ++ | |
| 6-35 | ++ | |
| 6-36 | ++ |
Table 78
| Example | IC 50 | vivo |
| 6-37 | ++ | |
| 6-38 | ++ | |
| 6-39 | ++ | + |
| 6-40 | ++ | |
| 6-41 | 12.3％(100) | |
| 6-42 | 21.7％(100) | |
| 6-43 | ++ | |
| 6-44 | ++ | |
| 6-45 | ++ | |
| 6-46 | ++ | |
| 6-47 | 41.1％(100) | |
| 6-48 | ++ | ++ |
| 6-49 | ++ | |
| 6-50 | ++ |
Table 79
| Example | IC 50 | In vivo |
| 7-1 | ++ | + |
| 7-2 | ++ | |
| 7-3 | ++ | |
| 7-4 | ++ | ++ |
| 7-5 | 8.5％(300) | |
| 7-7 | 2.9％(300) | |
| 7-8 | 6.8％(300) | |
| 7-10 | ++ | ++ |
| 7-11 | 47.3％(100) | |
| 7-12 | 8.0％(100) | |
| 7-13 | 1.9％(100) | |
| 7-14 | 4.6％(100) | |
| 7-15 | ++ | |
| 7-16 | ++ |
Industrial utilizability
Can be confirmed by above-mentioned result of the test, but the human liver glycogen phosphorylase of admissible salt strong inhibition on compound of the present invention and the pharmacology thereof. Therefore, the compounds of this invention can be effectively as the new medicine for treating diabetes based on this new mechanism of action of GP inhibitory action. In addition, the compounds of this invention and other medicine for treating diabetes or hyperlipidemia curative and time spent also are expected to obtain corresponding effect, and as the therapeutic agent of insulin resistance disease, diabetic neuropathy, nephrosis, diabetic keratopathy retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidemia, atheroma arteriosclerosis, tissue ischemia disease, myocardial ischemia disease; Appetite regulation therapeutic agent and for the therapeutic agent of obesity; The serviceability that bacillary, fungoid, parasitic physical property or viral infection disease etc. are infected Remedies is unusual Worth Expecting also.
Claims (57)
1. treatment of diabetes or prophylactic compositions, it contains admissible salt and pharmaceutically permissible carrier on the pyrazole compound of following general formula (I) expression or its pharmacology,
Wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4And R
5Identical or different respectively, expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
Wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41'
Can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms,
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
Wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411'
Can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms,
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl;
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl,
This cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring;
(6) C
3-8Cycloalkyl C
1-6Alkyl,
This C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring;
(7) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52，
R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3,
(8) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
This C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces,
D5.-N(R
53)(R
53’)、
Wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl,
D6.-CO-N(R
531)(R
531’)、
Wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl,
D7.-COOR
54、
Wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl,
D8.-C(NH(OH))＝N-R
55、
Wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl,
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement;
(9) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
Wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces,
(10) C
7-14Aralkyl,
This C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces,
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl,
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl,
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl or.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(11) be selected from the C of identical or different more than one substituting group replacement that condenses the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent and these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino,
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
Wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.
In addition, above-mentioned R
4And R
5Can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring, in addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
2. treatment of diabetes according to claim 1 or prophylactic compositions, it contains admissible salt and pharmaceutically permissible carrier on the pyrazole compound of following general formula (I) expression or its pharmacology,
Wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-4Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4Expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R4
11)(R4
11’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(6) C
3-8Cycloalkyl C
1-6Alkyl; Perhaps
(7) aryl;
R
5Expression
(1) can be selected from the C that the more than one substituting group of following group of B replaces
1-6Alkyl;
[group B]
B1. hydroxyl,
B2.C
1-6Alkoxyl group,
B3.-N(R
51)(R
51’)、
(wherein, R
51And R
51' identical or different, expression hydrogen atom or C
1-6Alkyl, R
51And R
51' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
And
B4.-CO-N(R
511)(R
511’)、
(wherein, R
511And R
511' identical or different, expression hydrogen atom or C
1-6Alkyl, R
511And R
511' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
(2) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(3) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(4) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52，
R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3;
(5) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
(6) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(7) C
7-14Aralkyl;
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces
C
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl,
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic aromatic heterocycle of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(8) C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6Alkyl or condensed the C that the aromatic heterocycle of formation replaces by these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino,
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
In addition, above-mentioned R
4And R
5Can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring.In addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
3. treatment of diabetes according to claim 1 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound of following general formula (II ') expression,
Wherein, R
1, R
2, R
3, R
4And R
5With claim 1 synonym.
4. treatment of diabetes according to claim 1 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound of following general formula (II) expression,
Wherein, R
4And R
5With claim 1 synonym, R
1aExpression halogen atom or hydrogen atom, R
2aThe expression halogen atom, R
3aExpression halogen atom or C
1-6Alkyl.
5. treatment of diabetes according to claim 4 or prophylactic compositions, wherein R
1aExpression hydrogen atom or fluorine atom, R
2aExpression fluorine atom or chlorine atom, R
3aExpression chlorine atom or C
1-6Alkyl.
6. treatment of diabetes according to claim 5 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound of following general formula (III) expression,
Wherein, R
4And R
5With above-mentioned synonym.
7. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-6
4Be to be selected from following group base,
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A ' replaces
1-6Alkyl;
[group A ']
A ' 1. hydroxyl,
A ' 2.C
1-4Alkoxyl group,
A’3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-4Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 4. phenyl,
A ' 5. five yuan or the monocyclic aromatic heterocycle of hexavalent,
A’6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-4Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A ' 7. carboxyl and
A ' 8.C
1-4Alkoxy carbonyl,
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl; And
(6) C
3-8Cycloalkyl C
1-4Alkyl;
8. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be C
1-6Alkyl.
9. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be C
3-8Cycloalkyl, this C
3-8Cycloalkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
10. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be C
3-8Cycloalkyl C
1-6Alkyl.
11. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be can be selected from acyl group and-CO-(Alk)
n-COOR
52More than one substituting group five yuan or the monocyclic saturated heterocyclyl of hexavalent, wherein R replacing
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.
12. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be the phenyl that can be selected from the more than one substituting group replacement of following group of D ',
[group D ']
D ' 1. can be by the C of carboxyl substituted
1-4Alkyl,
D’2.-CO-N(R
53)(R
53’)，
Wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-4Alkyl or C
1-4Alkyl sulphonyl,
D’3.-COOR
54、
Wherein, R
54Be hydrogen atom, C
1-4Alkyl, C
1-4Alkyl-carbonyl oxygen base C
1-4Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-4Alkyl,
And
D ' 4. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
13. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5Be C
7-14Aralkyl, this C
7-14The aryl moiety of aralkyl can be replaced by the more than one substituting group of following group of F ',
[group F ']
F ' 1.C
1-6Alkyl,
F ' 2. halogen atom,
F ' 3. cyano group,
F ' 4. hydroxyl,
F ' 5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F ' is halo C 6.
1-6Alkyl,
F ' 7. carboxyl,
F ' 8.C
1-6Alkoxy carbonyl,
F’9.-CO-N(R
56a)(R
56a’)、
Wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f '
1-6Alkyl,
[group f ']
F ' 1. amino,
The 2. single C of f '
1-6Alkylamino,
F ' is two C 3.
1-6Alkylamino,
F ' 4. carboxyl,
F ' 5.C
1-6Alkoxy carbonyl,
F ' is hydroxyl 6.
And
F ' 7. has five yuan or the monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms,
F’10.-N(R
56b)(R
56b’)、
Wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl,
F’11.-N＝CR
57(-N(R
58)(R
58’))、
Wherein, R
57Expression hydrogen atom or C
1-4Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-4Alkyl,
12. 5 yuan of F ' or the monocyclic aromatic heterocycle of hexavalent,
And
F ' 13. methylene radical dioxy bases or ethylidene dioxy base.
14. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-7
5The C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6The more than one substituting group that alkyl, this aromatic heterocycle can be selected from following group of G ' replaces,
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' 2. amino,
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
Wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, in addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces,
G’7.-CO-N(R
59b)(R
59b’)、
Wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl,
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
15. according to each described treatment of diabetes or prophylactic compositions, wherein R among the claim 2-6
5And R
4Form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring, in addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
16. treatment of diabetes according to claim 2 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound of following general formula (IV) expression,
Wherein, R
4With claim 2 synonym, R
X1, R
X2, R
X3Respectively identical or different, the expression hydrogen atom or be selected from following group of F " substituting group, m represents 0 or the integer of 1-2,
[group F "]
F " 1.C
1-6Alkyl,
F " 2. halogen atom
F " 3. cyano group
F " 4. hydroxyl
F " 5. can be selected from carboxyl and C
1-4The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F " 6. halo C
1-6Alkyl,
F " 7. carboxyl,
F " 8.C
1-6Alkoxy carbonyl,
F”9.-CO-N(R
56a)(R
56a’)，
Wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from following group of f " the C that replaces of more than one substituting group
1-6Alkyl,
[group f "]
F " 1. amino,
F " 2. single C
1-6Alkylamino,
F " 3. two C
1-6Alkylamino,
F " 4. carboxyl,
F " 5.C
1-6Alkoxy carbonyl,
F " 6. hydroxyl
And
F " 7. have five yuan or a monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms,
F”10.-N(R
56b)(R
56b’)、
Wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, can be inferior by the amino C that replaces
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl,
F”11.-N＝CR
57(-N(R
58)(R
58’))、
Wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl,
F " 12. 5 yuan or the monocyclic aromatic heterocycle of hexavalent,
And
F " 13. methylene radical dioxy bases or ethylidene dioxy base.
17. treatment of diabetes according to claim 2 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound that following logical formula V is represented,
Wherein, R
4With claim 2 synonym, ring Het represents five yuan or the monocyclic aromatic heterocycle of hexavalent, R
Y1, R
Y2, R
Y3Respectively identical or different, expression hydrogen atom or be selected from the substituting group of following group of G ', the integer of m ' expression 0 or 1-2,
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' 2. amino,
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
Wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, in addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces,
G’7.-CO-N(R
59b)(R
59b’)、
Wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl,
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
18. treatment of diabetes according to claim 17 or prophylactic compositions wherein encircle Het and represent pyridine ring, triazole ring or azoles ring.
19. treatment of diabetes according to claim 18 or prophylactic compositions, wherein pyrazole compound is the pyrazole compound of following general formula (VI) expression,
Wherein, R
4, R
Y1, R
Y2, R
Y3, m ' and above-mentioned synonym.
20. treatment of diabetes according to claim 2 or prophylactic compositions, wherein admissible salt is selected from following group on pyrazole compound or its pharmacology,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides 3/2 hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides L-(+)-tartrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl) acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diethylamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-cyclohexyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenoxy group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two fluoro-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-trifluoromethyl-benzamide
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-the benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-tertiary butyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-dimethylamino-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-sec.-propyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-6-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-oxyethyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(pyridin-3-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1H-benzimidazolyl-2 radicals-ylmethyl)-acid amides dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-ritalin,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-methyl propionate
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-pair-(2-acetoxyl group ethyl)-amino-ethyl formamyl]-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-hydroxyl-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-{2-[(2-acetoxyl group ethyl)-(2-hydroxyethyl)-amino]-the ethylamino formyl radical }-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-benzimidazolyl-2 radicals-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzothiazole-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-pyrroles-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,4-dimethoxy-pyridine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (the 5-tertiary butyl-thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-2-phenyl-2H-[1,2,3] triazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(tert-butoxycarbonyl-amino)-methyl-pyridine-2-ylmethyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-methyl-2-(morpholine-4-yl)-thiazole-5-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides 3/2 hydrochloride 1/2 hydrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethoxy carbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibenzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (cyano group-phenyl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hydroxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl amide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid allyl group-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(1-methyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [(3,4-methylenedioxyphenyl base)-methyl]-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(4-hydroxyl-butyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibutyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid is two-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopentyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(3-methoxyl group-propyl group)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-oxyethyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-isopropoxy-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-propoxy--ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethyl-propyl group)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-tert-butoxycarbonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethanoyl-piperidin-4-yl)-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-methylsulfonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-ethoxalyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxalic acid one acyl group-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1,1-dioxy-six hydrogen-1 λ
6-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxygen-six hydrogen-1 λ
4-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid propyl group-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-formamyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-oxalic acid one acyl group-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-carboxyl ethanoyl-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(2-carboxypropanoyl)-piperidin-4-yl]-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclobutyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl methyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-carboxyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-ethoxy carbonyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1H-pyrazol-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridine-2-base-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-3-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-4-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid pyrazine-2-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-methyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-hydroxyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-methyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-hydroxyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two bromo-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethyl-2-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-ethyl-4-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ([2,2 '] dithio phenyl-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methoxyl group-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl- azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hexyl-4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-thiene-3-yl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-2-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-4-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-hexyl-2-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenyl-thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenoxy group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(pyridin-3-yl)-ethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (xenyl-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1R, 2S)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1S, 2R)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-2-pyridone-3-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-piperazine-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid styroyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-styroyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroisoquinoline-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroquinoline-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid amyl group-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diphenyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridine-2-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (furans-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxycarbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-trifluoromethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-dimethylamino-ethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,6-dimethoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxycarbonyl methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-carboxyl methoxyl group-benzamide,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides,
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid sec.-propyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (ethoxy carbonyl-methyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (carboxyl-methyl)-phenyl-acid amides,
5-(2-chloro-4-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-oxygen-2-(piperidines-1-yl)-ethyl]-phenyl-acid amides,
5-(5-fluoro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-methoxyl group-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-ethyl)-phenyl-acid amides,
5-(2-fluoro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-2,6-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-3-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethylamino formyl radical methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isobutyl--phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxycarbonyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-ethoxy carbonyl-propyl group)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-carboxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-propyl group)-phenyl-acid amides,
5-(2-hydroxyl-4-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-hydroxy-5-methyl oxygen base-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-hydroxyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-phenyl-acid amides,
5-(2,5-dimethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-pyridine-2-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,6-two chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl-phenyl)-acid amides,
5-(2-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-6-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-pyridine-4-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(morpholine-4-base formamyl)-benzamide dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-acetic acid sodium salt,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-propionic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(morpholine-4-base formamyl)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[2-(morpholine-4-yl)-ethylamino formyl radical]-the pyridin-4-yl methyl]-the acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-base formamyl)-pyridin-4-yl methyl]-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides 1/2 vitriol
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-amino methyl-pyridine-2-ylmethyl)-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dimethanesulfonate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(morpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-diethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-2-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 5-methyl-pyrazine-2-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-methylpiperazine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-dimethylamino-piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(tetramethyleneimine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid carbamyl ylmethyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formamyl-phenyl)-methyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(4-methylamino formyl radical-phenyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formyl-dimethylamino-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(4H-[1,2,4] triazole-3-yl)-phenyl]-amide hydrochloride,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(N-hydroxyl carbamimidoyl)-phenyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-2,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2,2-dimethyl-propionyl oxygen base)-methoxycarbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[N-(methoxyl group-thiocarbonyl oxygen base)-carbamimidoyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-sulfo--4,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-4,5-dihydro-[1,2,4] thiadiazoles-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(cyclohexyl oxygen base-ketonic oxygen base)-ethoxy carbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-thiazol-2-yl)-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-cyano group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(toluene-4-sulfuryl amino)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-6-fluoro-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-4,5-two fluoro-benzamide hydrochloride salts,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (7-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-4H-quinazoline-3-yl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-2-methyl isophthalic acid, 4-dihydro-2H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(N-hydroxyl carbamimidoyl)-pyridin-4-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(5-oxygen-4,5-dihydro-[1,2,4] diazole-3-yl)-pyridin-4-yl methyl]-acid amides,
4-{[5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,6-two chloro-5-fluoro-pyridine-3-carbonylaminos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-benzo [b] thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-benzoyl-amido-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-phenyl acetyl amino-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-amino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methylsulfonyl amino-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-acetylamino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3,4,5-three chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(1H-tetrazolium-5-yl)-pyridin-4-yl methyl]-acid amides and
1H-pyrazoles-3,5-dicarboxylic acid 3-benzamide 5-[(2,4-two chloro-phenyl)-acid amides].
21. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the claim 1-20 or prophylactic compositions and other Remedies for diabetes or preventive.
22. medicine according to claim 21, wherein other Remedies for diabetes or preventive are insulin preparation (injections), low molecule oral insulin agent, sulfonylurea receptor stimulant (SU agent), the non-sulfonylurea insulin secretion stimulators, the agent of potassium dependency ATP (KATP) access portal, the α alpha-glucosidase inhibitors, the αDian Fenmei inhibitor, insulin sensitivity enhancer, low molecule tGLP-1 receptor stimulant, the tGLP-1 peptide analogs, DPP IV (DPP-IV) inhibitor, glucagon receptor antagonist, glucocorticoid receptor antagonists, the biguanides agent, the SGLUT inhibitor, fructose-1,6-bisphosphatase (FBPase) inhibitor, Glycogen Synthase kinase 3 (GSK-3) inhibitor, phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, protein tyrosine phosphatase esterase IB (PTPase 1B) inhibitor, inositol monophosphate esterase (SHIP2) inhibitor that contains the SH2 zone, glycogen phosphorylase (GP) inhibitor, glucokinase activators, the GPR40 receptor stimulant, pyruvic dehydrogenase kinase (PDHK) inhibitor, glutamine: fructose-6-phosphate transaminase (GFAT) inhibitor, antioxidant; Nitric oxide scavengers, carnitine palmityl transferase 1 (carnitine palmitoyltransferase, CPT-1) inhibitor, growth releasing factor (GHRF), triacylglycerol lipase (hormone-sensitive lipase) inhibitor, PPAR γ receptor stimulant, PPAR γ receptor antagonist, PPAR α/γ receptor stimulant, AMP-sensitization protein kinase (AMPK) activator, adiponectin receptor stimulant or β
3Adrenoceptor agonists.
23. according to claim 21 or 22 described medicines, wherein other Remedies for diabetes or preventive are Regular Insulin, tolbutamide, glyclopyramide, tsiklamid, P-607, glybuzole, Glyburide, gliclazid, gsh, mitiglinide, repaglinide, nateglinide, voglibose, acarbose, miglitol, rosiglitazone maleate, Walaphage, U-72107A or Ziavetine.
24. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the claim 1-20 or prophylactic compositions and other diabetic complications therapeutical agent or preventive.
25. medicine according to claim 24, wherein other diabetic complications therapeutical agent or preventive are protein kinase β (PKC β) inhibitor, angiotensin II receptor antagonists, aldose reductase inhibitor, angiotensin-converting enzyme (ACE) inhibitor, saccharification final product (AGE) generation inhibitor, neuropathy remedies or diabetic nephropathy therapeutical agent.
26. according to claim 24 or 25 described medicines, wherein other diabetic complications therapeutical agent or preventive are epalrestat, mexiletine hydrochloride or hydrochloric acid imidapril.
27. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the claim 1-20 or prophylactic compositions and other remedy for hyperlipemia or preventive.
28. medicine according to claim 27, wherein other remedy for hyperlipemia is fibrate class medicament (a PPAR α receptor stimulant), the PPAR delta receptor agonist, microsomal triglyceride transfer protein (MTP) inhibitor, cholesteryl ester transfer protein (CETP) inhibitor, statin class medicament (HMG-CoA reductase inhibitor), anionite-exchange resin, probucol, nicotinic acid class medicament, plant sterol, apolipoproteins-A1 (Apo-A1) inductor, lipoprotein lipase (LPL) activator, the endodermis lipase inhibitor, ezetimibu, ibat inhibitor, inhibitor for squalene synthetic enzyme, the ACAT inhibitor, the lxr receptor agonist, the FXR receptor stimulant, FXR receptor antagonist or adenosine A 1 agonist.
29. according to claim 27 or 28 described medicines, wherein other remedy for hyperlipemia is clofibrate, bezafibrate, fenofibrate, lovastatin, Simvastatin, Pravastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin, Cerivastatin, Colestyramine, courage ammonium fat, tocopheryl nicotinate, nicomol, pentaerythritol tetranicotinate, stigmasterol or γ orizanol disappear.
30. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the claim 1-20 or prophylactic compositions and other anti-obesity therapeutical agent or preventive.
31. medicine according to claim 30, wherein other anti-obesity therapeutical agent or preventive are the leptin preparations; pancreatic lipase inhibitor; the norepinephrine serotonin reuptake inhibitors; the cannabinoid receptor antagonist; monoamine re-uptake inhibitor; diacylglycerol acyltransferase (DGAT) inhibitor; glucose dependency insulin secretion promotes polypeptide (GIP) receptor antagonist; the leptin receptor stimulant; bombasin receptor subtype 3 (BRS-3) agonist; the perilipin inhibitor; acetyl-CoA carboxylase 1 (ACC1) inhibitor; acetyl-CoA carboxylase 2 (ACC2) inhibitor; fatty acid synthase inhibitor; sn-1-acyl group-glycerol-3-phosphate acyltransferase (AGPAT) inhibitor; pancreatic phospholipase A2 (pPLA2) inhibitor; melanocortin (MC) receptor stimulant; neuropeptide Y 5 (NPY5) receptor antagonist; Uncoupling Proteins (UCP) inductor or activator; CPT1 (CPT-1) activator; CCK1 (CCKA) agonist; ciliary neurotrophic factor (CNTF); the CRF2 agonist; neuropeptide Y 2 (NPY2) receptor antagonist; neuropeptide tyrosine 4 (NPY4) receptor antagonist; the Thyroid Hormone Receptors beta-agonists; the growth hormone; the atp citrate lyase inhibitors; 5-HT6 antagonist or 5-HT2C agonist.
32. according to claim 30 or 31 described medicines, wherein other anti-obesity therapeutical agent or preventive are leptin, orlistat, sibutramine, rimonabant or Mazindol.
33. a medicine, it is combined to form by the treatment of diabetes that will put down in writing among the claim 1-20 or prophylactic compositions and other therapeutic agent for hypertension or preventive.
34. medicine according to claim 33, wherein other therapeutic agent for hypertension or preventive are thiazide diuretics, the similar diuretic(s) of thiazides, loop diuretic, K retentivity diuretic(s), Beta receptor blockers, α, Beta receptor blockers, alpha blocker, the central sympathetic inhibitor, tip sexual intercourse sense nerous sedative (Radix Rauvolfiae preparation), Ca antagonist (benzothiazepin class), Ca antagonist (dihydropyridines), vasodilator, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor antagonists, the nitric acid agent, endothelin ETA receptor antagonist, the endothelin-converting enzyme inhibitor; Neprilysin inhibitor, prostaglandin(PG); Prostanoid FP agonist, hypertension fibrinogen inhibitor, NOS3 express intensifying factor; Prostacyclin analogue, Phosphodiesterase V (PDE5A) inhibitor, prostacyclin analogue or aldosterone antagonist.
35. according to claim 33 or 34 described medicines, wherein other therapeutic agent for hypertension or preventive are Zestoretics, trichloromethiazide, the Wyovin Zestoretic, the sulphonamide chroman, indapamide, tripamide, chlortalidone, Mefrusal, furosemide, antisterone, triamterene, Target, the bisoprolol fumarate, the hydrochloric acid betaxolol, bevantolol hydrochloride, metoprolol tartrate, Acebutolol, Celiprolol Hydrochorid, nipradolol, N-696, nadolol, propranolol hydrochloride, the hydrochloric acid indenolol, carteolol hydrochloride, pindolol, pindolol continues releasing agent, Betriol (Boehringer,Ing.), penbutolol sulfate, bopindolol malonate, amosulalol hydrochloride, hydrochloric acid arotinolol, carvedilol, labetalol hydrochloride, urapidil, Vasocard, the methylsulfonic acid element, E-643, PRAZOSINI HYDROCHLORIDE, phentolamine mesilate, Tenso-Timelets, guanidine hydrochloride method is new, guanabenz acetate, methyldopa, serpentine, rescinnamine, Phenylsulfonic acid A Muluohe, Aranidipine, efonidipine, cilnidipineb, nicardipine hydrochloride, nisoldipine, nitrendipine, nifedipine, nifedipine continues releasing agent, nilvadipine, Bamidipine Hydrochloride, felodipine, KW-3049, CV-4093, Azelnidipine, diltiazem hydrochloride, hydrazine hydrochloride, hydrochloric acid todoralazine, budralazine, cadralazine, captopril, enalapril maleate, alacepril, delapril hydrochloride, Yipingshu, lisinopril, benazepril hydrochloride, the hydrochloric acid imidapril, hydrochloric acid tamocapril, quinapril hydrochloride, Trolapril, perindopril elbumin, candesartan cilexetil, valsartan, telmisartan, Olmesartan, medoxomil, sodium nitroprusside, perhaps nitroglycerine.
36. admissible salt on the pyrazole compound of following general formula (I) expression or its pharmacology.
Wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4And R
5Identical or different respectively, expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl.
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(6) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(7) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52。
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(8) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
(9) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(10) C
7-14Aralkyl;
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl.
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl,
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base.
(11) be selected from the C of identical or different more than one substituting group replacement that condenses the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent and these aromatic heterocycles and phenyl ring
1-6Alkyl;
(wherein, this aromatic heterocycle can be selected from the more than one substituting group replacement of following group of G.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino,
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms.In addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. can be by five yuan or the monocyclic saturated heterocyclyl of hexavalent of oxygen base or sulfenyl replacement.
In addition, above-mentioned R
4And R
5Can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring, in addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
37. admissible salt on pyrazole compound according to claim 36 or its pharmacology, it is with following general formula (I) expression,
Wherein,
Ring Q represents aryl or aromatic heterocycle;
R
1Expression hydrogen atom, halogen atom, C
1-6Alkyl or C
1-6Alkoxyl group;
R
2Expression halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group or azido-;
R
3Expression halogen atom, hydroxyl, C
1-6Alkyl, halo C
1-6Alkyl, C
1-6Alkoxyl group, azido-, amino, acyl amino or C
1-6Alkyl sulfonyl-amino;
R
4Expression
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A replaces
1-6Alkyl;
[group A]
A1. hydroxyl,
A2.C
1-6Alkoxyl group,
A3.-N(R
41)(R
41’)、
(wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-6Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A4. aryl,
A5. aromatic heterocycle,
A6.-CO-N(R
411)(R
411’)、
(wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-6Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
A7. carboxyl,
And
A8.C
1-6Alkoxy carbonyl,
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl;
(6) C
3-8Cycloalkyl C
1-6Alkyl; Perhaps
(7) aryl;
R
5Expression
(1) can be selected from the C that the more than one substituting group of following group of B replaces
1-6Alkyl;
[group B]
B1. hydroxyl,
B2.C
1-6Alkoxyl group,
B3.-N(R
51)(R
51’)、
(wherein, R
51And R
51' identical or different, expression hydrogen atom or C
1-6Alkyl, R
51And R
51' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
And
B4.-CO-N(R
511)(R
511’)、
(wherein, R
511And R
511' identical or different, expression hydrogen atom or C
1-6Alkyl, R
511And R
511' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms.)
(2) C
3-8Cycloalkyl;
(this cycloalkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense by pyridine ring.)
(3) C
3-8Cycloalkyl C
1-6Alkyl;
(this C
3-8Cycloalkyl C
1-6The cycloalkyl of alkyl can be by hydroxyl, carboxyl or C
1-6Alkoxy carbonyl replaces, and perhaps can condense with pyridine ring.)
(4) can be selected from five yuan or the monocyclic saturated heterocyclyl of hexavalent that the more than one substituting group of following group of C replaces;
[group C]
C1.C
1-6Alkyl,
C2. acyl group,
C3.C
1-6Alkyl sulphonyl,
C4. carboxyl,
C5.C
1-6Alkoxy carbonyl,
And
C6.-CO-(Alk)
n-COOR
52，
(R wherein
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.)
(5) can be selected from the aryl that the more than one substituting group of following group of D replaces;
[group D]
D1. hydroxyl,
D2.C
1-6Alkoxyl group,
D3. cyano group,
D4.C
1-6Alkyl,
(this C
1-6Alkyl can be selected from hydroxyl, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.)
D5.-N(R
53)(R
53’)、
(wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D6.-CO-N(R
531)(R
531’)、
(wherein, R
531And R
531' identical or different, expression hydrogen atom, C
1-6Alkyl or C
1-6Alkyl sulphonyl.)
D7.-COOR
54、
(wherein, R
54Be hydrogen atom, C
1-6Alkyl, C
1-6Alkyl-carbonyl oxygen base C
1-6Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-6Alkyl.)
D8.-C(NH(OH))＝N-R
55、
(wherein, R
55Expression hydrogen atom or C
1-6Alkyl sulphonyl.)
D9. five yuan or the monocyclic saturated heterocyclyl of hexavalent,
And
D10. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
(6) condense the aromatic heterocycle of formation as five yuan or the monocyclic aromatic heterocycle of hexavalent or these aromatic heterocycles and phenyl ring;
(wherein, this aromatic heterocycle can be selected from carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces)
(7) C
7-14Aralkyl;
(this C
7-14One or two substituting group that the moieties of aralkyl can be selected from following group of E replaces, and the more than one substituting group that aryl moiety also can be selected from following group of F replaces.)
[group E]
E1. the C that can be replaced by hydroxyl
1-6Alkyl,
E2. cyano group,
E3. carboxyl,
E4.C
1-6Alkoxy carbonyl,
And
E5. phenyl,
[group F]
F1.C
1-6Alkyl,
F2. halogen atom,
F3. cyano group,
F4. hydroxyl,
F5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F6. halo C
1-6Alkyl,
F7. carboxyl,
F8.C
1-6Alkoxy carbonyl,
F9.-CO-N(R
56a)(R
56a’)、
(wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from the C that the more than one substituting group of following group of f replaces
1-6Alkyl.)
[group f]
F1. amino,
F2. single C
1-6Alkylamino,
F3. two C
1-6Alkylamino,
F4. carboxyl
F5.C
1-6Alkoxy carbonyl,
F6. hydroxyl
And
F7. five yuan or the monocyclic saturated heterocyclyl of hexavalent having at least one nitrogen-atoms.
F10.-N(R
56b)(R
56b’)、
(wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl.)
F11.-N＝CR
57(-N(R
58)(R
58’))、
(wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-6Alkyl.)
F12. five yuan or the monocyclic aromatic heterocycle of hexavalent,
F13. methylene radical dioxy base or ethylidene dioxy base,
(8) C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6Alkyl or condensed the C that the aromatic heterocycle of formation replaces by these aromatic heterocycles and phenyl ring
1-6Alkyl;
(the more than one substituting group that this aromatic heterocycle can be selected from following group of G replaces.)
[group G]
G1. can be selected from the C of the more than one substituting group replacement of following group of g
1-6Alkyl,
[group g]
G1. halogen atom,
G2. amino,
G3. single C
1-6Alkylamino,
G4. two C
1-6Alkylamino,
G5.C
1-6Alkoxycarbonyl amino,
And
G6. oxyimino,
G2. halogen atom,
G3. the C that can be replaced by halogen atom
1-6Alkoxyl group,
G4. aryloxy,
G5. cyano group,
G6.-N(R
59a)(R
59a’)、
(wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, in addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces.)
G7.-CO-N(R
59b)(R
59b’)、
(wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl.)
G8. aryl
And
G9. five yuan or the monocyclic aromatic heterocycle of hexavalent that can be replaced by oxygen base or sulfenyl, in addition, above-mentioned R
4And R
5Can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, wherein, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring, in addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
38. admissible salt on pyrazole compound according to claim 36 or its pharmacology, it is with following general formula (II ') expression,
Wherein, R
1, R
2, R
3, R
4And R
5With claim 36 synonym.
39. admissible salt on pyrazole compound according to claim 36 or its pharmacology, it is with following general formula (II) expression,
Wherein, R
4And R
5With claim 36 synonym, R
1aExpression halogen atom or hydrogen atom, R
2aThe expression halogen atom, R
3aExpression halogen atom or C
1-6Alkyl.
40. according to admissible salt, wherein R on the described pyrazole compound of claim 39 or its pharmacology
1aExpression hydrogen atom or fluorine atom, R
2aExpression fluorine atom or chlorine atom, R
3aExpression chlorine atom or C
1-6Alkyl.
41. according to admissible salt on the described pyrazole compound of claim 40 or its pharmacology, wherein pyrazole compound is the pyrazole compound of following general formula (III) expression,
Wherein, R
4And R
5With claim 37 synonym.
42. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-41
4Be to be selected from following group base,
(1) hydrogen atom;
(2) can be selected from the C that the more than one substituting group of following group of A ' replaces
1-6Alkyl;
[group A ']
A ' 1. hydroxyl,
A ' 2.C
1-4Alkoxyl group,
A’3.-N(R
41)(R
41’)、
Wherein, R
41And R
41' identical or different, expression hydrogen atom or C
1-4Alkyl, R
41And R
41' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms,
A ' 4. phenyl,
A ' 5. five yuan or the monocyclic aromatic heterocycle of hexavalent,
A’6.-CO-N(R
411)(R
411’)、
Wherein, R
411And R
411' identical or different, expression hydrogen atom or C
1-4Alkyl, R
411And R
411' can form five yuan or the monocyclic saturated heterocyclic of hexavalent with adjacent nitrogen-atoms,
A ' 7. carboxyl and
A ' 8.C
1-4Alkoxy carbonyl,
(3) C
2-6Thiazolinyl;
(4) C
2-6Alkynyl;
(5) C
3-8Cycloalkyl; And
(6) C
3-8Cycloalkyl C
1-4Alkyl;
43. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be C
1-6Alkyl.
44. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be C
3-8Cycloalkyl, this C
3-8Cycloalkyl can be selected from hydroxyl, carboxyl or C
1-6The more than one substituting group of alkoxy carbonyl replaces.
45. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be C
3-8Cycloalkyl C
1-6Alkyl.
46. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be can be selected from acyl group and-CO-(Alk)
n-COOR
52-five yuan or the monocyclic saturated heterocyclyl of hexavalent, wherein R that individual above substituting group replaces
52Be hydrogen atom or C
1-6Alkyl, Alk are C
1-4Alkylidene group, n are 0 or the integer of 1-3.
47. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be the phenyl that can be selected from the more than one substituting group replacement of following group of D ',
[group D ']
D ' 1. can be by the C of carboxyl substituted
1-4Alkyl,
D’2.-CO-N(R
53)(R
53’)、
Wherein, R
53And R
53' identical or different, expression hydrogen atom, C
1-4Alkyl or C
1-4Alkyl sulphonyl,
D’3.-COOR
54、
Wherein, R
54Be hydrogen atom, C
1-4Alkyl, C
1-4Alkyl-carbonyl oxygen base C
1-4Alkyl or C
3-8Cycloalkyl oxy ketonic oxygen base C
1-4Alkyl,
And
D ' 4. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
48. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5Be C
7-14Aralkyl, this C
7-14The aryl moiety of aralkyl can be replaced by the more than one substituting group of following group of F ',
[group F ']
F ' 1.C
1-6Alkyl,
F ' 2. halogen atom,
F ' 3. cyano group,
F ' 4. hydroxyl,
F ' 5. can be selected from carboxyl and C
1-6The C that the more than one substituting group of alkoxy carbonyl replaces
1-6Alkoxyl group,
F ' is halo C 6.
1-6Alkyl,
F ' 7. carboxyl,
F ' 8.C
1-6Alkoxy carbonyl,
F’9.-CO-N(R
56a)(R
56a’)、
Wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or be selected from the C of the more than one substituting group replacement of following group of f '
1-6Alkyl,
[group F ']
F ' 1. amino,
The 2. single C of f '
1-6Alkylamino,
F ' is two C 3.
1-6Alkylamino,
F ' 4. carboxyl,
F ' 5.C
1-6Alkoxy carbonyl,
F ' is hydroxyl 6.
And
F ' 7. has five yuan or the monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms,
F’10.-N(R
56b)(R
56b’)、
Wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl,
F’11.-N＝CR
57(-N(R
58)(R
58’))、
Wherein, R
57Expression hydrogen atom or C
1-4Alkyl, R
58And R
58' identical or different respectively, expression hydrogen atom or C
1-4Alkyl,
12. 5 yuan of F ' or the monocyclic aromatic heterocycle of hexavalent,
And
F ' 13. methylene radical dioxy bases or ethylidene dioxy base.
49. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-42
5The C that is replaced by the monocyclic aromatic heterocycle of five yuan or hexavalent
1-6The more than one substituting group that alkyl, this aromatic heterocycle can be selected from following group of G ' replaces,
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' 2. amino,
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
Wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, in addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces,
G’7.-CO-N(R
59b)(R
59b’)、
Wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl,
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
50. according to admissible salt, wherein R on each described pyrazole compound or its pharmacology among the claim 37-41
4And R
5Form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, this saturated heterocyclyl can have two keys in the part, can also condense the formation fused rings with phenyl ring, in addition, can condense this saturated heterocyclyl that forms fused rings with phenyl ring and can be selected from halogen atom, C
1-6Alkyl, C
1-6Alkoxyl group, carboxyl and C
1-6The more than one substituting group of alkoxy carbonyl replaces.
51. according to admissible salt on the described pyrazole compound of claim 37 or its pharmacology, wherein pyrazole compound is the pyrazole compound of following general formula (IV) expression,
Wherein, R
4With claim 37 synonym, R
X1, R
X2, R
X3Respectively identical or different, the expression hydrogen atom or be selected from following group of F " substituting group, m represents 0 or the integer of 1-2,
[group F "]
F " 1.C
1-6Alkyl,
F " 2. halogen atom,
F " 3. cyano group,
F " 4. hydroxyl,
F " 5. can be selected from carboxyl and C
1-4The C that the more than one substituting group of alkoxy carbonyl replaces
1-4Alkoxyl group,
F " 6. halo C
1-6Alkyl,
F " 7. carboxyl,
F " 8.C
1-6Alkoxy carbonyl,
F”9.-CO-N(R
56a)(R
56a’)、
Wherein, R
56aAnd R
56a' identical or different, the expression hydrogen atom, have five yuan of at least one nitrogen-atoms or the monocyclic saturated heterocyclyl of hexavalent or can be selected from following group of f " the C that replaces of more than one substituting group
1-6Alkyl,
[group f "]
F " 1. amino,
F " 2. single C
1-6Alkylamino,
F " 3. two C
1-6Alkylamino,
F " 4. carboxyl,
F " 5.C
1-6Alkoxy carbonyl,
F " 6. hydroxyl
And
F " 7. have five yuan or a monocyclic saturated heterocyclyl of hexavalent of at least one nitrogen-atoms,
F”10.-N(R
56b)(R
56b’)、
Wherein, R
56bAnd R
56b' identical or different, expression hydrogen atom, the C that can be replaced by imino-
1-6Alkyl, can be selected from aralkyl that the identical or different more than one substituting group of imino-and halogen atom replaces, can be by C
1-6Aryl sulfonyl, C that alkyl replaces
1-6Alkyl sulphonyl, acyl group, formamyl, single C
1-6Alkyl-carbamoyl or two C
1-6Alkyl-carbamoyl,
F”11.-N＝CR
57(-N(R
58)(R
58’))、
Wherein, R
57Expression hydrogen atom or C
1-6Alkyl, R
58And R
58' identical or different, expression hydrogen atom or C
1-6Alkyl,
F " 12. 5 yuan or the monocyclic aromatic heterocycle of hexavalent,
And
F " 13. methylene radical dioxy bases or ethylidene dioxy base.
52. according to admissible salt on the described pyrazole compound of claim 37 or its pharmacology, wherein pyrazole compound is the pyrazole compound that following logical formula V is represented,
Wherein, R
4With above-mentioned synonym, ring Het represents five yuan or the monocyclic aromatic heterocycle of hexavalent, R
Y1, R
Y2, R
Y3Respectively identical or different, expression hydrogen atom or be selected from the substituting group of following group of G ', the integer of m ' expression 0 or 1-2,
[group G ']
G ' 1. can be selected from the C of the more than one substituting group replacement of following group of g '
1-6Alkyl,
[group g ']
G ' 1. halogen atom,
G ' 2. amino,
The 3. single C of g '
1-6Alkylamino,
G ' is two C 4.
1-6Alkylamino,
G ' 5.C
1-6Alkoxycarbonyl amino,
And
G ' 6. oxyimino,
G ' 2. halogen atom,
The C that G ' 3. can be replaced by halogen atom
1-6Alkoxyl group,
G ' 4. aryloxy,
G ' 5. cyano group,
G’6.-N(R
59a)(R
59a’)、
Wherein, R
59aAnd R
59a' identical or different, expression hydrogen atom or C
1-6Alkyl, R
59aAnd R
59a' can form five yuan or the monocyclic saturated heterocyclyl of hexavalent with adjacent nitrogen-atoms, in addition, this saturated heterocyclyl also can be selected from hydroxyl, amino, single C
1-6Alkylamino and two C
1-6The more than one substituting group of alkylamino replaces,
G’7.-CO-N(R
59b)(R
59b’)、
Wherein, R
59bAnd R
59b' identical or different, be hydrogen atom, five yuan or the monocyclic saturated heterocyclyl of hexavalent or the C that can be replaced by this heterocyclic radical
1-6Alkyl,
G ' is aryl 8.
And
G ' 9. can be by five yuan or the monocyclic aromatic heterocycle of hexavalent of oxygen base or sulfenyl replacement.
53., wherein encircle Het and represent pyridine ring, triazole ring or azoles ring according to admissible salt on the described pyrazole compound of claim 52 or its pharmacology.
54. according to admissible salt on the described pyrazole compound of claim 53 or its pharmacology, wherein pyrazole compound is the pyrazole compound of following general formula (VI) expression,
Wherein, R
4, R
Y1, R
Y2, R
Y3, m ' and above-mentioned synonym.
55. according to admissible salt on the described pyrazole compound of claim 37 or its pharmacology, wherein admissible salt is selected from following group on pyrazole compound or its pharmacology,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl)-acid amides 3/2 hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl- azoles-5-ylmethyl) acid amides L-(+)-tartrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides p-tosylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl) acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diethylamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-cyclohexyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-dimethoxy-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,3-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,4-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3,5-two fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenoxy group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two fluoro-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-trifluoromethyl-benzamide
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-trifluoromethyl-benzamide,
5-(2-chloro-4,5-two fluoro-the benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-tertiary butyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-isopropoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-dimethylamino-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-sec.-propyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-6-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-oxyethyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(2,2,2-three fluoro-oxyethyl groups)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-dimethyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(pyridin-3-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1H-benzimidazolyl-2 radicals-ylmethyl)-acid amides dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-ritalin,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-methyl propionate
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-pair-(2-acetoxyl group ethyl)-amino-ethyl formamyl]-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(2-hydroxyl-ethylamino formyl radical)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-{2-[(2-acetoxyl group ethyl)-(2-hydroxyethyl)-amino]-the ethylamino formyl radical }-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-benzimidazolyl-2 radicals-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (benzothiazole-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-thiazole-4-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid H-pyrroles-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,4-dimethoxy-pyridine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (the 5-tertiary butyl-thiazol-2-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-2-phenyl-2H-[1,2,3] triazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(tert-butoxycarbonyl-amino)-methyl-pyridine-2-ylmethyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-methyl-2-(morpholine-4-yl)-thiazole-5-ylmethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides 3/2 hydrochloride 1/2 hydrate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-fluoro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethoxy carbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibenzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (cyano group-phenyl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hydroxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl amide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid allyl group-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(1-methyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [(3,4-methylenedioxyphenyl base)-methyl]-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(4-hydroxyl-butyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-cyclohexyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid dibutyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid is two-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-(tetrahydrochysene-pyrans-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopentyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(3-methoxyl group-propyl group)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-oxyethyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-isopropoxy-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-propoxy--ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethyl-propyl group)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-tert-butoxycarbonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(tetrahydrochysene-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-ethanoyl-piperidin-4-yl)-butyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-methylsulfonyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-ethoxalyl-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxalic acid one acyl group-piperidin-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1,1-dioxy-six hydrogen-1 λ
6-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(1-oxygen-six hydrogen-1 λ
4-thiapyran-4-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid propyl group-(pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-diethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-ethylamino formyl radical-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-formamyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-oxalic acid one acyl group-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-carboxyl ethanoyl-piperidin-4-yl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(2-carboxypropanoyl)-piperidin-4-yl]-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclobutyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclopropyl methyl-(6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-carboxyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-(2-ethoxy carbonyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2,6-two chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1H-pyrazol-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridine-2-base-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-3-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-pyridin-4-yl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid pyrazine-2-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-methyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [3-oxyethyl group-5-(1-ethoxy carbonyl-1-hydroxyl-ethyl)-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-methyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [5-(1-carboxyl-1-hydroxyl-ethyl)-3-oxyethyl group-pyridine-2-yl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two bromo-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethyl-2-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-ethyl-4-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ([2,2 '] dithio phenyl-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methoxyl group-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,5-two chloro-thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,5-dimethyl- azoles-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-hexyl-4-methyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-thiene-3-yl-methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-2-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-4-phenyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-hexyl-2-methyl- azoles-5-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-[1,2,4] triazole-3-ylmethyl)-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-6-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-4,6-dimethyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (5-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-pyridine-2-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-phenyl-thiazole-4-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenoxy group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-chloro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [1-(pyridin-3-yl)-ethyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-fluoro-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (xenyl-3-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1R, 2S)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((1S, 2R)-2-hydroxyl-indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-phenyl-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methyl-2-pyridone-3-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-piperazine-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-piperidines-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid styroyl acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-styroyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroisoquinoline-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-α-methoxycarbonyl-phenmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,2,3,4-tetrahydroquinoline-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenyl-propyl group-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid amyl group-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid diphenyl-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridine-2-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((R)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ((S)-2-hydroxyl-1-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (furans-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiophene-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-dimethylamino-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-dimethylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-chloro-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-methoxycarbonyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-carboxyl-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-trifluoromethyl-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethyl-(2-dimethylamino-ethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid cyclohexyl-(2-dimethylamino-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxyl group-pyridine-2-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,6-dimethoxy-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methoxycarbonyl methoxyl group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-carboxyl methoxyl group-benzamide,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl- azoles-5-ylmethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl phenyl)-methyl-acid amides,
4-{[5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid sec.-propyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (ethoxy carbonyl-methyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (carboxyl-methyl)-phenyl-acid amides,
5-(2-chloro-4-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid phenmethyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1-methyl isophthalic acid-phenyl-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-oxygen-2-(piperidines-1-yl)-ethyl]-phenyl-acid amides,
5-(5-fluoro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-methoxyl group-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-2-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-ethyl)-phenyl-acid amides,
5-(2-fluoro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-chloro-2-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-2,6-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-3-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid ethylamino formyl radical methyl-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isobutyl--phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxycarbonyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-ethoxy carbonyl-propyl group)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-carboxyl-ethyl)-phenyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3-carboxyl-propyl group)-phenyl-acid amides,
5-(2-hydroxyl-4-methoxyl group-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-hydroxy-5-methyl oxygen base-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-hydroxyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(5-fluoro-2-trifluoromethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-methoxyl group-ethyl)-phenyl-acid amides,
5-(2,5-dimethyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-5-methyl-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(4-chloro-pyridine-2-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2,6-two chloro-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl-phenyl)-acid amides,
5-(2-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-6-methyl-pyridine-3-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(3-chloro-pyridine-4-carbonylamino)-1H-pyrazoles-3-carboxylic acid benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-ethoxy carbonyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid butyl-(4-carboxyl methyl-phenyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methoxycarbonyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-carboxyl-phenyl)-(2-methoxyl group-ethyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (thiazole-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(morpholine-4-base formamyl)-benzamide dihydrochloride,
[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-acetic acid sodium salt,
3-[4-({ [5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-amino }-methyl)-benzoyl-amido]-propionic acid sodium salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (1,3,5-trimethylammonium-1H-pyrazoles-4-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethyl-different azoles-4-ylmethyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[2-(morpholine-4-yl)-ethylamino formyl radical]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(morpholine-4-base formamyl)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[2-(morpholine-4-yl)-ethylamino formyl radical]-the pyridin-4-yl methyl }-the acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(morpholine-4-base formamyl)-pyridin-4-yl methyl]-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-acid amides 1/2 vitriol
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-dimethoxy-pyridin-4-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-amino methyl-pyridine-2-ylmethyl)-acid amides tri hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides mesylate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-pyridin-3-yl methyl)-acid amides dimethanesulfonate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-methoxyl group-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(morpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (3,5-two chloro-pyridin-4-yl methyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-dimethylamino-pyridin-3-yl methyl)-propyl group-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-diethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-chloro-2-dimethylamino-pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-[1,2,3] thiadiazoles-4-base-phenmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2,4-dimethyl-thiazole-5-ylmethyl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-hydroxy-piperdine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 5-methyl-pyrazine-2-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid quinoline-8-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid isoquinoline 99.9-5-base acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-methylpiperazine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(4-dimethylamino-piperidines-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(tetramethyleneimine-1-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyrazine-2-ylmethyl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(thiomorpholine-4-yl)-pyridin-3-yl methyl]-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [6-(1,1-dioxy-1 λ
6-thiomorpholine-4-yl)-the pyridin-3-yl methyl]-the acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid carbamyl ylmethyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formamyl-phenyl)-methyl-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-(4-methylamino formyl radical-phenyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-formyl-dimethylamino-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-methylsulfonyl aminocarboxyl-phenyl)-methyl-chlorseptol,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(4H-[1,2,4] triazole-3-yl)-phenyl]-amide hydrochloride,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid (4-cyano group-phenyl)-methyl-acid amides,
5-(4-azido--2-chloro-5-fluoro-benzoyl-amido)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [4-(N-hydroxyl carbamimidoyl)-phenyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-2,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2,2-dimethyl-propionyl oxygen base)-methoxycarbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[N-(methoxyl group-thiocarbonyl oxygen base)-carbamimidoyl]-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-sulfo--4,5-dihydro-[1,2,4] diazole-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(5-oxygen-4,5-dihydro-[1,2,4] thiadiazoles-3-yl)-phenyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(cyclohexyl oxygen base-ketonic oxygen base)-ethoxy carbonyl]-phenyl }-methyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4-ethoxy carbonyl-thiazol-2-yl)-ethyl-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-methylsulfonyl amino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylamino-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(dimethylamino-methene amido)-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[1-(dimethylamino) ethyleneimino]-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(diethylamino-methene amido)-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-acetylimino-amino-benzamide dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-cyano group-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-[(2-fluoro-benzimidoyl)-amino]-the benzamide hydriodate,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 3-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 4-(3,3-dimethyl-urea groups)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-(toluene-4-sulfuryl amino)-benzamide,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-6-fluoro-benzamide hydrochloride salt,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid 2-amino-4,5-two fluoro-benzamide hydrochloride salts,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-1-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (indane-2-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (7-fluoro-4H-quinazoline-3-yl)-acid amides dihydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (6-fluoro-4H-quinazoline-3-yl)-amide hydrochloride,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-oxyethyl group-2-methyl isophthalic acid, 4-dihydro-2H-quinazoline-3-yl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(N-hydroxyl carbamimidoyl)-pyridin-4-yl methyl]-acid amides,
5-(2-chloro-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(5-oxygen-4,5-dihydro-[1,2,4] diazole-3-yl)-pyridin-4-yl methyl]-acid amides,
4-{[5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carbonyl]-methyl-amino }-the phenylformic acid sodium salt,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid methyl-[4-(1H-tetrazolium-5-yl)-phenyl]-acid amides,
5-(2,4-two chloro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,4-two chloro-5-fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2,6-two chloro-5-fluoro-pyridine-3-carbonylaminos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-benzo [b] thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3-chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-benzoyl-amido-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-phenyl acetyl amino-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-methyl-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides dihydrochloride,
5-(2-amino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methylsulfonyl amino-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(2-acetylamino-4,5-two fluoro-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-[(3,4,5-three chloro-thiophene-2-carbonyl)-amino]-1H-pyrazoles-3-carboxylic acid (pyridin-3-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid (2-cyano group-pyridin-4-yl methyl)-acid amides,
5-(4,5-two fluoro-2-methyl-benzoyl-amidos)-1H-pyrazoles-3-carboxylic acid [2-(1H-tetrazolium-5-yl)-pyridin-4-yl methyl]-acid amides and
1H-pyrazoles-3,5-dicarboxylic acid 3-benzamide 5-[(2,4-two chloro-phenyl)-acid amides].
56. the therapeutical agent or the preventive of an insulin resistance disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataract, hypercholesterolemia, vascular hypertension, hyperinsulinemia, hyperlipidaemia, atheroma arteriosclerosis, tissue ischemia disease, myocardial ischemia disease, obesity or bacillary, fungoid, parasitic rerum natura or viral infection disease, it is an effective constituent with admissible salt on the pyrazole compound of any one record among the claim 36-55 or its pharmacology.
57. a medicine, its by will be in the claim 56 therapeutical agent of record or preventive and other drug regimen form.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP148847/2005 | 2005-05-23 | ||
| JP2005148847 | 2005-05-23 | ||
| US60/685,037 | 2005-05-26 | ||
| JP367286/2005 | 2005-12-20 | ||
| US60/755,820 | 2006-01-03 |
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| Publication Number | Publication Date |
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| CN101208306A true CN101208306A (en) | 2008-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800181941A Pending CN101208306A (en) | 2005-05-23 | 2006-05-22 | Pyrazole compounds and antidiabetes agents containing the same |
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| CN (1) | CN101208306A (en) |
| ZA (1) | ZA200710097B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104072441A (en) * | 2014-07-04 | 2014-10-01 | 山东誉衡药业有限公司 | Method for preparing epalrestat |
| CN108299405A (en) * | 2018-02-12 | 2018-07-20 | 李化绪 | 3- is to N, N diethylaminos phenylimino class compound and its application in hyperlipidemia |
| CN108707143A (en) * | 2018-06-26 | 2018-10-26 | 孟晓旭 | A kind of DPP-4 inhibitor and its preparation and the application in diabetes |
| CN114478333A (en) * | 2022-01-28 | 2022-05-13 | 宜春新龙智慧高科有限公司 | Synthetic method and application of 2, 2' -dithio-dibenzoyl formamide |
-
2006
- 2006-05-22 CN CNA2006800181941A patent/CN101208306A/en active Pending
- 2006-05-22 ZA ZA200710097A patent/ZA200710097B/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104072441A (en) * | 2014-07-04 | 2014-10-01 | 山东誉衡药业有限公司 | Method for preparing epalrestat |
| CN104072441B (en) * | 2014-07-04 | 2016-08-31 | 山东誉衡药业有限公司 | A kind of preparation method of epalrestat |
| CN108299405A (en) * | 2018-02-12 | 2018-07-20 | 李化绪 | 3- is to N, N diethylaminos phenylimino class compound and its application in hyperlipidemia |
| CN108707143A (en) * | 2018-06-26 | 2018-10-26 | 孟晓旭 | A kind of DPP-4 inhibitor and its preparation and the application in diabetes |
| CN114478333A (en) * | 2022-01-28 | 2022-05-13 | 宜春新龙智慧高科有限公司 | Synthetic method and application of 2, 2' -dithio-dibenzoyl formamide |
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|---|---|
| ZA200710097B (en) | 2009-10-28 |
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