WO1999046232A1 - Derives d'acide carboxylique et medicaments contenant ces derives comme principe actif - Google Patents
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- WO1999046232A1 WO1999046232A1 PCT/JP1999/001134 JP9901134W WO9946232A1 WO 1999046232 A1 WO1999046232 A1 WO 1999046232A1 JP 9901134 W JP9901134 W JP 9901134W WO 9946232 A1 WO9946232 A1 WO 9946232A1
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- acetic acid
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- phenylmethylthio
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07C62/30—Unsaturated compounds
- C07C62/34—Unsaturated compounds containing ether groups, groups, groups, or groups
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- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
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- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
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- C07C59/40—Unsaturated compounds
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Definitions
- the present invention relates to a dicarboxylic acid derivative and a drug containing the derivative as an active ingredient.
- the present invention relates to a peroxisome proliferator-activated receptor modulator comprising a porphyric acid derivative and a porphyrin derivative as active ingredients.
- the present invention relates to an agent, a novel carboxylic acid derivative represented by the general formula (I), a non-toxic salt thereof, a hydrate thereof, and a method for producing them.
- PPAR receptor nuclear receptor Peroxisome Proliferator Activated Receptor
- type 7 is mainly expressed in adipose tissue, immune cells, adrenal gland, spleen, and small intestine, and cast is mainly expressed in adipose tissue, liver, and retina, and type is ubiquitously expressed without tissue specificity. (See Endocrinology., 137. 354 (1996)).
- the thiazolidine derivatives shown below are known as therapeutic agents for non-insulin-dependent diabetes mellitus (NIDDM), and are hypoglycemic agents used to correct hyperglycemia in diabetic patients. It is also a compound that has been shown to be extremely promising as an insulin sensitizer because it is effective in correcting or improving hyperinsulinemia, improving glucose tolerance, and lowering serum lipids.
- NIDDM non-insulin-dependent diabetes mellitus
- PPARa receptor which increases the transcriptional activity of PPAR7 (Endocrinology., 121, 4189 (1996); Cell “S3, 803 (1995); CeU., 83, 813 (1995); J. Biol. Chem., 270, 12953 (1995)), thus increasing the transcriptional activity of PPAR7.
- the activated PPARa activator (agonist) is considered to be promising as a hypoglycemic agent and / or a lipid lowering agent.
- PPARa activator agonist
- the nuclear receptor PPAR is involved in adipocyte differentiation (J. Biol. Chem., 222,
- PPARa receptor activator agonist
- PPARa protein expression regulator that can increase the expression of protein itself are hypoglycemic, lipid lowering, diabetes, obesity, syndrome X, Useful as a prophylactic and therapeutic agent for hypercholesterolemia, hyperlipoproteinemia and other metabolic disorders, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease, bulimia, etc. Power s expected.
- antagonists that suppress the transcriptional activity of the PPARa receptor or PPARa protein expression regulators that can suppress the expression of the protein itself include hypoglycemic agents, diabetes, obesity, metabolic disorders such as syndrome X, and hyperlipidemia. Is expected to be useful as a prophylactic and / or therapeutic agent for diseases, arteriosclerosis, hypertension, bulimia and the like.
- fibrous compounds for example, clofibrate, are known as lipid lowering agents
- PPARa receptor One of the intracellular target proteins of fibrate compounds has also been found to be the PPARa receptor (Nature., 347, 645 (1990); J. Steroid Biochem. Molec. Biol, 51, 157 (1994); Biochemistry., 32, 5598 (1993)). Based on these facts, it is considered that a modulator of PPAR receptor which can be activated by a fibrate compound has a lipid-lowering effect, and is useful as a preventive and / or therapeutic agent for hyperlipidemia, etc. Is expected.
- HDL cholesterol elevating effect LDL cholesterol and Z or VLDL cholesterol decreasing effect
- LDL cholesterol and Z or VLDL cholesterol decreasing effect It is expected to be effective in the treatment and prevention of obesity, and as a hypoglycemic agent, it is also promising for the treatment and prevention of diabetes, the improvement of hypertension, the reduction of the risk factor of syndrome X, and the prevention of the development of ischemic heart disease.
- PPAR S is sometimes referred to as P PAR / ?, or NUC 1 in humans.
- hNUC IB a PPAR subtype that differs from human NUC1 by one amino acid
- compounds (agonists) having high affinity for PPARS protein and significantly activating PPARS have been found. (High-density lipoprotein) It was reported that it had a cholesterol-elevating effect.
- agonists capable of activating PPAR S are expected to have an effect of raising HDL cholesterol, thereby suppressing the progression of arterial sclerosis, and its application, as a lipid-lowering agent and hypoglycemic agent, Is thought to be useful for the treatment of diabetes, hypoglycemic drugs, treatment of diabetes mellitus, reduction of the risk factor of syndrome X, and prevention of ischemic heart disease o
- WO 9728115 discloses the general formula (A)
- R 1A is selected from a hydrogen atom, C 3-10 cycloalkyl, etc.
- R 2 A is selected from a hydrogen atom, C 5-10 aryl, C 5-10 heteroaryl, etc.
- R 4A is R 2 A (ZA— W A—) represents Z A — CR6AR7A, or ZA—CR 6AR7 A—R 8A— etc.
- R 8 A is CR 6A R7 A, ⁇
- R6A and R7A are each independently selected from a hydrogen atom and C1-6 alkyl
- XIA and X2A are each independently a hydrogen atom, a C1-15 alkyl
- YA is selected from S (0) ⁇ ⁇ , one 0- like
- Upsilon 1 Alpha is selected from 0, C, etc.
- Zetaarufa is selected from CO 2 R 3 Alpha, etc.
- t A And VA each independently represent 0 or 1 tA + vA represents
- AB is phenyl, said phenyl being one or more halogen atoms, C1-6 alkyl, C1-3 alkoxy, C1-3 fluoroalkoxy, nitrile or monoNR7BR8B (R 7 B and R 8 B are each independently hydrogen Represents an atom or C 1-3 alkyl. ) May be substituted with
- BB represents a 5- or 6-membered heterocyclic ring C 1-6 alkylene containing at least one heteroatom selected from an oxygen atom, a nitrogen atom and a sulfur atom; May be substituted with C 1-3 alkyl;
- a 1 k B represents C 1-3 alkylene
- R 1 B represents a hydrogen atom or C 1-3 alkyl
- ZB is selected from 1- (Cl-3 alkylene) phenyl or 1NR3BR4B. ) Or a pharmaceutically acceptable salt thereof is described as having PPAR 7 agonist activity (the description of the groups in the formulas was excerpted from necessary parts).
- R'C is an optionally substituted aromatic hydrocarbon group, an optionally substituted cycloaliphatic hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted heterocyclic group.
- R 5 C is a lower alkyl group.
- R 4 C is a hydrogen atom or a lower alkyl group
- R 6 C is a hydrogen atom or Forms a double bond together with R 9 C
- R 7 ′ C is a hydrogen atom, a hydroxy group, a carboxy group, an acyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted lower alkyl group , Replaced Optionally substituted rubamoyl group, an optionally substituted aryloxycarbonyl group, an optionally substituted arylalkyloxycarbonyl group or a group represented by the general formula: YC—R8 C
- YC is one NH— or an oxygen atom
- R8C is an optionally substituted acyl group, an optionally substituted alkoxycarbonyl group, an aryloxycarbonyl group or an aralkyloxycarbonyl group.
- R 9 C is a hydrogen atom, an optionally substituted lower alkyl group or an optionally substituted lower alkoxycarbonyl group
- R 10C is a hydroxy group, an optionally substituted lower alkoxycarbonyl group.
- a pharmaceutical composition containing a propionic acid derivative represented by the formula or a pharmaceutically acceptable salt thereof has a blood sugar lowering action and a blood lipid lowering action.
- compounds similar to JP-A-8-325264, JP-A-8-325250, W09638415, and WO980000137 also show a blood glucose lowering effect and blood It is described as having a lipid lowering effect.
- RD represents a hydrocarbon residue or a heterocyclic group which may be bonded via a carbon chain
- nD is 0 or 1
- XD is CH or N
- YD is R 1 D and R 2 D are the same or different and each represents a hydrogen atom, a halogen atom, an optionally substituted hydroxyl group, or an optionally substituted hydrocarbon residue.
- R 1D either as R2D and some Y D It may combine with each other to form a ring.
- the compound represented by the formula (1) or a salt thereof has a blood glucose lowering effect and a blood lipid lowering effect (for the explanation of the groups in the formula, necessary parts were extracted.).
- Japanese Patent Application Laid-Open No. 61-85372 also discloses that similar compounds have a hypoglycemic action and a lipid-lowering action.
- WE is a bond or one 0—, one S— or one NR4E—, m E is 1 to: 1 5.
- R4E is each independently hydrogen or lower alkyl, and R 7 E is hydrogen or methyl. I do.
- a pharmaceutically acceptable salt thereof is described as having a lipoxygenase inhibitory activity and a leukotriene antagonistic activity.
- Japanese Patent Application Laid-Open No. 8-504194 describes the general formula (F) X F one ⁇ ⁇ _ ⁇ fire " ⁇ Li - Le Fu _ A F _ B F ( F)
- aryl F is a monocyclic aromatic six-membered ring system containing 0, 1, 2, 3, or 4 N atoms and having no substituents or substituted with R 5 F. Yes;
- XF contains 0, 1, 2, 3 or 4 heteroatoms selected from N, 0, S and has no substituent or R 1 F , R 2 F, R 3 F or R 4 A monocyclic or polycyclic aromatic or non-aromatic 4- to 10-membered ring system substituted with F;
- R1F, R2F, 1 ⁇ 3? ⁇ ⁇ 4? Are hydrogen, C1-10 alkyl, ⁇ 3-8 cycloalkyl, aryl C0-8 alkyl, amino C0-8 alkyl, Cl Independently selected from the group consisting of -6 alkylamino C0-8 alkyl, C1-6 dialkylamino C0-8 alkyl, C1-4 alkoxy C0-6 alkyl, and the like;
- nF is an integer of 0 to 2 And
- ZF and AF is (CH 2) M F, ( CH 2) M F_ ⁇ (CH 2) ⁇ ⁇ , ( CH 2) M F S0 2 (CH 2) NF, (CH 2) MF S (CH 2) NF , (CH 2 ) MF SO (CH 2 ) n F, etc., where mF and nF are integers independently selected from 0 to 6, provided that AF is (CH 2 ) mF
- the "Aryl F" ring combined with ZF and AF must contain at least one heteroatom;
- R 5 F is hydrogen, C 1-6 alkyl, C 0-6 alkyloxy C 0-6 alkyl, or halogen;
- R6F, R 7 F, R8F, R 9F, R 10 F , and R 11 F are independently selected from hydrogen, C 1 to 8 Al kill like,
- R12F is selected from hydroxy, C1-8 alkyloxy and the like. It has been described that the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof has fiprinogen receptor antagonistic activity (the explanation of the groups in the formula is excerpted from necessary parts). Disclosure of the invention
- the present inventors have conducted intensive studies to find a compound having a PPAR receptor regulating action, and as a result, have found that the compound represented by the general formula (I) achieves the object, and completed the present invention.
- Some of the compounds represented by the general formula (I) are already known in the above-mentioned JP-A-1-143856 and JP-A-8-504194, and their actions, namely, lipoxygenase It is also known to have an inhibitory activity on lipase, a leukotriene antagonistic activity, and a fibrinogen receptor antagonistic activity, but from these facts, it is not expected that a PPAR receptor controlling action is expected. Some of the compounds represented by the general formula (I) are novel compounds which have not been known so far.
- the present invention is a.
- a 1 represents a 1 to 4 alkylene group or a C 2 to 4 alkenylene group
- a 2 represents a 10-group or a S-group
- a 3 represents a CH group or an N group
- n 1 to 5
- (X) represents a C 1-4 alkylthio group
- R 7 , R 8 and R 9 are each independently a hydrogen atom, or C 1-4 alkyl Represents a group.
- R 4 shall bind to position 2 or 3;
- a peroxisome proliferator-activated receptor modulator comprising a carboxylic acid derivative represented by the formula, a non-toxic salt thereof, or a hydrate thereof as an active ingredient;
- a iC represents a 1-4 alkylene group or a C 2-4 alkenylene group
- A2 represents a 10-group or a 1-S group
- a 3 represents a CH group or an N group
- n 1 to 5
- (X) represents a C 1-4 alkylthio group
- R 7 , R 8 and R 9 each independently represent a hydrogen atom or a C 1-4 alkyl group.
- R 4 shall bind to position 2 or 3;
- a 4 represents a single bond or methylene
- 83 represents (11, and Cyc 1 represents benzene, A 1 represents methylene, ethylene, or vinylene.
- the alkyl group, the alkenyl group, the alkynyl group, the alkoxy group, the alkylthio group, the alkylene group, the alkenylene group and the alkynylene group include those having a straight or branched chain.
- isomers in double bonds, rings and fused rings include those having a straight or branched chain.
- the C1-4 alkyl group is a methyl, ethyl, propyl, butyl group and isomers thereof.
- the C1-8 alkyl group is a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl group and isomers thereof.
- the C 1-4 alkoxy group includes methoxy, ethoxy, propoxy, butoxy and isomers thereof.
- the C 1-4 alkylthio group is a methylthio, ethylthio, propylthio, butylthio group and isomers thereof.
- the C1-4 alkylene group is a methylene, ethylene, trimethylene, tetramethylene group or an isomer thereof.
- the C2-4 alkenylene group is an ethenylene, propenylene, butenylene group or an isomer thereof.
- Halogen atoms are iodine, bromine, fluorine and chlorine.
- the trihalomethyl group is a methyl group tri-substituted by an iodine atom, a bromine atom, a fluorine atom, and a chlorine atom.
- the trihalomethoxy group is a methoxy group trisubstituted by an iodine atom, a bromine atom, a fluorine atom, and a chlorine atom.
- Trihalomethylthio group means iodine atom, bromine atom, fluorine atom, chlorine atom Is a methylthio group tri-substituted by
- the carbocycle represents a C3 to C15 monocyclic, bicyclic, tricyclic carbocyclic or bridged carbocyclic ring.
- Examples of the C3-I5 monocyclic, bicyclic, tricyclic carbocyclic and bridged carbocyclic rings include, for example, cycloprono, cyclohexane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane , Cyclodecane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene, pentalene, indene, naphthalene, azulene, fluorene, phenanthrene, anthracene, asenaphthylene, biphenylene, perhydropentalene, indane (dihydroindene) , Perhydr
- a heterocyclic ring is a 4- to 18-membered monocyclic, bicyclic or tricyclic heteroaryl or aryl having 1-4 nitrogen atoms, 1-2 oxygen atoms and one or one sulfur atom. Includes those partially or wholly saturated.
- the above-mentioned 4- to 18-membered monocyclic, bicyclic or tricyclic heterocyclic ring containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or one sulfur atom is partially or entirely saturated.
- Examples of the sum include pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, dihydropyridine, dihydropyrazine, dihydropyrimidine, dihydropyridazine, pyridine, pyrazine, tetrahydropyrimidine, and tetrahydropyrimidine.
- R 2 is preferably a C 1-4 alkyl group, particularly preferably a methyl group and an ethyl group.
- Cyc 1 is preferably
- a 1 is preferably a C 1-4 alkylene group, particularly preferably a C 1-2 alkylene group (one CH 2 — group, one (CH 2 ) 2 — group). Yes o
- a 2 is preferably a 10-group.
- a 3 is preferably a CH group.
- the preferred bonding position of R 4 is the 3-position.
- R 4 is preferably a ——A 4 —C—COOR group.
- a 4 is preferably a single bond or a C 1-4 alkylene 10- group or a C 1-4 alkylene S- group, particularly preferably a single bond, or One CH 2 —S— group.
- R 8 and R 9 are preferably a hydrogen atom or a methyl group, and particularly preferably a hydrogen atom.
- R 1 is preferably a hydrogen atom, a C 1-8 alkyl group, a halogen atom, a trihalomethoxy group or a trihalomethylthio group, and particularly preferably a hydrogen atom, a halogen atom or a trihalomethoxy group.
- the carbocycle represented by Cyc2 is preferably a C3-10 monocyclic or bicyclic carbocycle, and more preferably cyclopropane, cyclobutane, cyclopentane, cyclo Hexane, cycloheptane, cyclooctane, cyclononane, cyclodecane or benzene, more preferably cyclopropane, cyclopentane, cyclohexane or benzene.
- the heterocyclic ring represented by Cyc2 is preferably a 5- to 10-membered heterocyclic ring having 1 to 2 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom.
- Monocyclic or bicyclic heterocyclic aryls or a part or all of them are saturated, more preferably furan, thiophene, pyridine, quinoline, thiadiazol (1,2,3-thiadiazol), Razine or dioxaindan (1,3-dioxindan), more preferably dioxinindane (1,3-dioxindan).
- the carbocycle represented by R 1 is preferably a C 3-10 monocyclic or bicyclic carbocycle, more preferably cyclopropane, cyclobuta Cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, cyclodecane or benzene, and more preferably cyclopropane, cyclopentane, cyclohexane or benzene.
- the heterocyclic ring represented by R 1 is preferably a 5- to 10-membered simple ring containing 1-2 nitrogen atoms, 1-2 oxygen atoms and / or one sulfur atom. Ring or bicyclic heterocyclic aryl or a part or all of which is saturated, more preferably furan, thiophene, pyridine, thiadiazol (1,2,3-thiadiazol), piperazine or dioxindan (1,3-dioxoindane), and more preferably thiadiazol (1,2,3-thiadiazol).
- the P PAR receptor controlling agent is a P PAR receptor “type, a type,
- the control mode is preferably a PPAR receptor model regulator, a PPAR receptor ⁇ type regulator, a PPAR receptor “type + a type regulator, or a PPAR receptor ⁇ type + S type regulator, and particularly preferred. Is a PPAR receptor ⁇ -type and ⁇ -type regulator or a PPAR-type regulator.
- PPAR receptor regulators also include PPAR receptor agonists and PPAR receptor antagonists, but are preferably PPAR receptor agonists, more preferably PPAR receptor prototype agonists, PPAR receptor agonists.
- a body type agonist, a PPAR receptor "type + type agonist, or a PPAR receptor type + agonist, particularly preferably a PPAR receptor type + type agonist, or a PPAR type 3 agonist is there.
- Specific compounds include the compounds described in Tables 1 to 20 below, their non-toxic salts or their hydrates.
- each R l-l and C 00 R 7- 1 has the same meaning as R l and C 00 R 7.
- the amino group represented by R 1-1 if the protection is necessary It assumed to be protected, as the C 00 H groups is assumed to be protected when protection is required.
- protecting groups Amino groups represented by C00R 7 one 1, for example, benzyl O alkoxycarbonyl group, It means t-butoxycarbonyl group, trifluoroacetyl group, etc.
- the protecting group of C00H group means, for example, methyl group, ethyl group, t-butyl group, benzyl group, etc. Other symbols are the same as above.
- R 11 represents a hydroxyl group or a mercapto group, and the other symbols have the same meanings as described above.).
- the reaction between the compound represented by the general formula ( ⁇ ) and the compound represented by the general formula ( ⁇ ) is known.
- a compound represented by the general formula ( ⁇ ) and a compound represented by the general formula ( ⁇ ) Solvents (methylene chloride, ether, tetrahydrofuran, acetate W / 4 nitrile, benzene, toluene, etc., azo compounds (ethyl azodicarboxylate, diisopropyl azodiphenol, 1,1,1- (azodicarbonyl) dipiperidine, 1, 1-azobis (N, N—
- the reaction is carried out by reacting at 0 ° (: up to 60 ° C for 3 to 20 hours) in the presence of dimethylformamide and phosphine compounds (triphenylphosphine, tributylphosphine, trimethylphosphine, etc.). Can be.
- the reaction of the compound represented by the general formula (IV) and the compound represented by the general formula (V) is known.
- the compound represented by the general formula (IV) and the compound represented by the general formula (V) are inactivated.
- Organic solvents tetrohydrofuran (THF), getyl ether, methylene chloride, chloroform, carbon tetrachloride, pentane, hexane, benzene, toluene, dimethylformamide (DMF), dimethylsulfoxide (DMSO),
- a base eg, sodium hydrogenated sodium, potassium carbonate, triethylamine, pyridine, cesium carbonate, etc.
- an additive eg, sodium fertilized sodium, potassium iodide, etc.
- the above reaction is known. For example, after reacting the compound represented by the general formula (VI) and thiourea in an organic solvent (methanol, ethanol, propanol, etc.) at o ° c to the reflux temperature of the solvent for 3 to 20 hours , An acid (concentrated sulfuric acid, etc.) and reacting at 0 ° C to the reflux temperature of the solvent for 3 to 20 hours.
- an organic solvent methanol, ethanol, propanol, etc.
- An acid concentrated sulfuric acid, etc.
- a compound represented by the general formula (1-1) is obtained by hydrolysis of the compound represented by the general formula (1-1). It can also be produced by subjecting to a deprotection reaction under acidic conditions or a deprotection reaction by hydrogenolysis. Deprotection reactions by alkali hydrolysis are known.
- hydroxides of alkali metals sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.
- organic solvent methanol, ethanol, tetrahydrofuran, dioxane, etc.
- Alkaline earth metal hydroxides barium hydroxide, calcium hydroxide, etc.
- carbonates sodium carbonate, potassium carbonate, etc.
- Deprotection reactions by hydrogenolysis include, for example, inert solvents [ether-based (eg, tetrahydrofuran, dioxane, dimethyloxetane, getyl-ether, etc.), alcohol-based (eg, methanol, ethanol, etc.), benzene-based (eg, Benzene, toluene, etc.), ketones (eg, acetone, methylethyl ketone, etc.), nitriles (eg, acetonitrile, etc.), amides (eg, dimethylformamide, etc.), water, ethyl acetate, Acetic acid or a mixed solvent of two or more thereof) in the presence of a hydrogenation catalyst (eg, palladium-carbon, palladium black, palladium, palladium hydroxide, platinum dioxide, nickel, Raney nickel, ruthenium chloride, etc.) , Inorganic acids (eg, hydrochloric acid,
- R 4 represents a 2,4-thiazolidinedione-1-yl group, and at least one of R 1 represents an amino group.
- R l-3 has the same meaning as R l. However, least one group of R 1-3 represents an amino group, the other symbols have the same meanings as described above.
- the deprotection reaction under acidic conditions or the deprotection reaction by hydrogenolysis can be carried out in the same manner as described above.
- the deprotection reaction means a general deprotection reaction that can be easily understood by those skilled in the art, for example, alkali hydrolysis, deprotection reaction under acidic conditions, deprotection reaction by hydrogenolysis, By properly using these reactions, the desired compound of the present invention can be easily produced.
- carboxyl protecting groups include methyl, ethyl, t-butyl and benzyl, but others can be easily and selectively removed. Any group that can be used is not particularly limited. For example, those described in T. Greene, Protective uroups in Organic Svnthesis, Wilev, New York, 1991 are used.
- Examples of the protecting group for the amino group include a benzyloxycarbonyl group, a t-butoxycarbonyl group, and a trifluoroacetyl group, but are not particularly limited as long as they can be easily and selectively eliminated. .
- a benzyloxycarbonyl group a t-butoxycarbonyl group
- a trifluoroacetyl group examples include T. W. Greene,
- the compounds represented by the general formulas (IV), (V) and (VI) can be produced by a method represented by the following reaction scheme.
- R 11-1 protected hydroxyl group or mercapto group
- A4-1 a single bond or a C1-4 alkylene group
- A4-2 -c1-4 alkylene-1 O- group or 1C1-4 alkylene-1S- group;
- TMS CN trimethylsilyl cyanide
- reaction product is purified by conventional purification means, for example, distillation under normal pressure or reduced pressure, high-performance liquid chromatography using silylation gel or magnesium silicate, thin-layer chromatography, Alternatively, it can be purified by a method such as column chromatography or washing and recrystallization. Purification may be performed for each reaction or may be performed after the completion of some reactions.
- the compounds described herein are converted to salts by known methods.
- the salt is preferably non-toxic and water-soluble.
- Suitable salts include salts of alkali metals (such as potassium and sodium), salts of alkaline earth metals (such as calcium and magnesium), ammonium salts, and pharmaceutically acceptable organic amines (tetramethylammonium). , Triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) aminomethane, lysine, arginine, N-methyl-1-D-glucamine) Salts.
- the compound of the present invention represented by the general formula (I) is converted into a corresponding acid addition salt by a known method.
- the acid addition salts are preferably non-toxic and water-soluble. Suitable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, or acetate, trifluoroacetate, lactate, tartrate, oxalate, Like fumarate, maleate, citrate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate Organic acid salts.
- the compound of the present invention or a non-toxic salt thereof described herein may be converted to a hydrate by a known method.
- TK thymidine kinase
- a response element of Ga14 protein, a basic transcription factor of yeast, and an enhancer sequence that repeats UAS four times are inserted upstream of the TK promoter to construct 4XUAS—TK—Lu. It was a gene.
- the enhancer sequence (SEQ ID NO: 1) used is shown below.
- Sequence number 1 Enhancer sequence which repeated Ga14 protein response element
- the nuclear receptor human P is located at the carboxyl terminus of the DNA binding region of the yeast Ga14 protein.
- a vector expressing a chimeric receptor protein fused with the ligand binding region of the PARa, ⁇ or S receptor was prepared as follows. That is, PicaGene Basic Vector 2 (trade name, Toyo Ink Co., Catalog No. 309-04821) was used as the basic expression vector, while the promoter-enhancer region was kept as it was, and the structural gene was replaced with that of the chimeric receptor protein.
- DNA encoding the amino acid sequence from the 1st to the 147th amino acid sequence of the DNA binding region of Ga14 protein is downstream of DNA encoding human PPAR, 7 or the ligand-binding region of the receptor. And inserted into PicaGene Basic Vector 2 (trade name) downstream of the promoter-enhancer region.
- a nuclear translocation signal derived from SV-40 T-antigen A1a Pro L ysLysLysArgLysVa1G1y (SEQ ID NO: 2), while the carboxy terminus is an epitope tag sequence for the detection of expressed proteins, and is a hemagglutinin peptide of influenza.
- the DNA sequence was such that a tope, TyrProTyrAsPValProAsPTyrAla (SEQ ID NO: 3) and a translation termination codon were arranged in this order.
- Human PPAR ⁇ ligand binding region Ser ⁇ 67—T y Human PPARa ligand binding region: Ser 6— ⁇ y r 478 Human PPAR ligand binding region: Ser 139—T yr
- CV-1 cells used as Luciferase atssii host cells using human PPARs / ⁇ / receptors were cultured according to standard methods. That is, fetal calf serum (GIBCOBRL, Catalog No. 26140-061) was added to Darbecco's modified Eagle's medium (DMEM) to a final concentration of 10%, and a final concentration of 50 UZ was added. The cells were cultured at 37 ° C. in 5% carbon dioxide gas on a medium containing m1 penicillin G and 50 g / m1 streptomycin sulfate.
- DMEM Darbecco's modified Eagle's medium
- the cells were dispersed by trypsinization and replated at 8000 cells / 100 ml DMEM—10% dialyzed serum / well at a cell density of well in a 96-well plate for several hours.
- 100 ⁇ l of a DMEM—10% dialyzed serum solution of the compound of the present invention containing twice the concentration of the assay was added.
- the cells were lysed and the luciferase activity was measured according to a conventional method.
- the positive control compound carbacycline (Eur. J. Biochem “233, 242 (1996); Genes & Development”), which can significantly activate the transcription of the luciferase gene against PP AR 10, 974 (1996))
- Table 21 shows the relative activity of 0.3% of the compound of the present invention when the luciferase activity at the time of adding 10 ⁇ M was 1.0.
- the positive control compound troglitazone (Cell., 83, 863 (1995), Endocrinology.), which can significantly activate the transcription of the luciferase gene with respect to PPAR7, is already marketed as a hypoglycemic agent. , 137, 4189 (1996) and J. Med. Chem., 39, 665 (1996))
- the luciferase activity at the time of addition of 10 ⁇ is 1.0
- the relative activity at the time of addition of 1.0 ⁇ l of the compound of the present invention is It is shown in Table 22.
- Table 23 shows the phase 1 "activity of the compound of the present invention, where the luciferase activity value at this time was 1.0.
- Example 2 (5) 0.8 Example 2 (1 1) 3.2 Example 2 (1 2) 1.7
- the blood sugar or lipid lowering effect in KKAyTa mice suggests a possibility as a preventive and / or therapeutic agent for diabetes and hyperlipidemia. It also has the effect of lowering blood cholesterol levels in high cholesterol diet-loaded rats and free fat.
- the acid-lowering effect suggests that it is useful as a prophylactic and / or therapeutic agent for arteriosclerosis.
- the compound of the present invention represented by the general formula (I), a non-toxic salt thereof, and a hydrate thereof have an activity of controlling a PPAR receptor, and have a hypoglycemic agent, a lipid-lowering agent, diabetes, Prevention and / or treatment of obesity, syndrome X, hypercholesterolemia, hyperlipoproteinemia and other metabolic disorders, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease, bulimia, ischemic heart disease, etc. Drugs, HDL cholesterol raising agents, LDL cholesterol and / or VLDL cholesterol lowering agents, and risk factor reducing agents for diabetes and Syndrome X are expected.
- the compound of the present invention represented by the general formula (I), a non-toxic salt thereof, and a hydrate thereof particularly have a PPARagonist action and / or a PPARagonist action.
- Hypoglycemic agents, lipid-lowering agents, diabetes, obesity, syndrome X, hypercholesterolemia, metabolic disorders such as hyperlipoproteinemia, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease, overeating Antihypertensive and Z or therapeutic agent, HDL cholesterol elevating effect, LDL cholesterol and / or VLDL cholesterol decreasing effect, and anti-arteriosclerosis progression and treatment, and obesity-suppressing effect are expected. It is expected to be used for treatment and prevention, improvement of hypertension, reduction of the risk factor of syndrome X, and prevention of ischemic heart disease.
- the compound of the present invention represented by the general formula (I), a non-toxic salt thereof, and a hydrate thereof have a PPAR8 agonist effect, and therefore have an HDL cholesterol-elevating effect, and It is expected to be used as a suppressor of curing progression and its treatment, as a lipid-lowering agent and hypoglycemic agent, as well as for the treatment of hyperlipidemia, hypoglycemic agents, treatment of diabetes mellitus, reduction of the risk factor of syndrome X, and reduction of hypoxia.
- the toxicity of the compound of the present invention is sufficiently low, and is considered to be sufficiently safe for use as a pharmaceutical.
- a non-toxic salt thereof, an acid addition salt thereof, or a hydrate thereof for the above-mentioned purpose, it is usually required to administer orally or non-systemically or locally. It is administered in oral form.
- Dosage varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but is usually in the range of 1 mg to 100 mg per day per adult, once to several times a day. Orally, or parenterally (preferably intravenously) once to several times daily, in a range of 0.1 mg to 100 mg per adult per person; or It is continuously administered intravenously for 1 to 24 hours a day.
- a dose smaller than the above-mentioned dose may be sufficient, or may be required to exceed the range.
- Solid preparations for oral administration include tablets, pills, capsules, powders, and granules.
- Capsules include hard capsules and soft capsules.
- one or more of the active substance (s) may be as is or excipients (lactose, mannitol, glucose, microcrystalline cellulose, starch, etc.), binders (hydroxypropylcellulose, Polyvinyl Mixed with rupyrrolidone, magnesium aluminate metasilicate, etc., disintegrants (calcium glycolate, etc.), lubricants (magnesium stearate, etc.), stabilizers, solubilizers (glutamic acid, aspartic acid, etc.) It is used in the form of a formulation according to a conventional method.
- a coating agent sucrose, gelatin, hydroxypropylcellulose, hydroxypropyl methylcellulose monophthalate, etc.
- capsules made of a material that can be absorbed, such as gelatin.
- Liquid preparations for oral administration include pharmaceutically acceptable solutions, suspensions, emulsions, syrups, elixirs and the like.
- one or more active substances are dissolved, suspended, or emulsified in a commonly used diluent (eg, purified water, ethanol, or a mixture thereof).
- this liquid preparation may contain a wetting agent, a suspending agent, an emulsifier, a sweetening agent, a flavoring agent, a fragrance, a preservative, a buffer and the like.
- Injections for parenteral administration include solutions, suspensions, emulsions, and solid injections that are dissolved or suspended in a solvent before use. Injectables are used by dissolving, suspending or emulsifying one or more active substances in a solvent.
- a solvent for example, distilled water for injection, physiological saline, vegetable oil, propylene glycol, polyethylene glycol, alcohols such as ethanol, or a combination thereof are used.
- this injection contains a stabilizer, a solubilizing agent (glutamic acid, aspartic acid, polysorbate 80 (registered trademark), etc.), a suspending agent, an emulsifier, a soothing agent, a buffer, a preservative, and the like. May be.
- a sterile solid preparation for example, a lyophilized product, can be manufactured and dissolved in aseptic or sterile distilled water for injection or other solvents before use.
- compositions for parenteral administration include topical solutions, ointments, salves, inhalants, sprays, suppositories, and the like, containing one or more active substances and prescribed in a conventional manner.
- Sprays may contain, in addition to the commonly used diluents, buffers that provide isotonicity with stabilizers such as sodium bisulfite, for example, isotonic agents such as sodium chloride, sodium citrate or citrate. It may be.
- Methods for producing sprays are described in detail, for example, in US Pat. Nos. 2,868,691 and 3,095,355. BEST MODE FOR CARRYING OUT THE INVENTION
- the solvent in the kakkou indicated by the separation point by chromatography and the TLC indicates the elution solvent or developing solvent used, and the ratio indicates the ratio.
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Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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AT99939188T ATE451346T1 (de) | 1998-03-10 | 1999-03-09 | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
DE69941777T DE69941777D1 (de) | 1998-03-10 | 1999-03-09 | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
EP99939188A EP1067109B1 (en) | 1998-03-10 | 1999-03-09 | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
JP2000535615A JP4345230B2 (ja) | 1998-03-10 | 1999-03-09 | カルボン酸誘導体およびその誘導体を有効成分として含有する薬剤 |
US09/623,913 US6506757B1 (en) | 1998-03-10 | 1999-03-09 | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
AU32759/99A AU3275999A (en) | 1998-03-10 | 1999-03-09 | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
US10/251,805 US7037914B2 (en) | 1998-03-10 | 2002-09-23 | Carboxylic acid derivative and a pharmaceutical composition containing the derivative as active ingredient |
US11/178,639 US7211591B2 (en) | 1998-03-10 | 2005-07-12 | Carboxylic acid derivative and a pharmaceutical composition containing the derivative as active ingredient |
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JP5844498 | 1998-03-10 | ||
JP10/58444 | 1998-03-10 | ||
JP8756098 | 1998-03-31 | ||
JP10/87560 | 1998-03-31 |
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US09623913 A-371-Of-International | 1999-03-09 | ||
US10/251,805 Division US7037914B2 (en) | 1998-03-10 | 2002-09-23 | Carboxylic acid derivative and a pharmaceutical composition containing the derivative as active ingredient |
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WO1999046232A1 true WO1999046232A1 (fr) | 1999-09-16 |
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PCT/JP1999/001134 WO1999046232A1 (fr) | 1998-03-10 | 1999-03-09 | Derives d'acide carboxylique et medicaments contenant ces derives comme principe actif |
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US (3) | US6506757B1 (ja) |
EP (1) | EP1067109B1 (ja) |
JP (1) | JP4345230B2 (ja) |
KR (1) | KR100620337B1 (ja) |
AT (1) | ATE451346T1 (ja) |
AU (1) | AU3275999A (ja) |
DE (1) | DE69941777D1 (ja) |
WO (1) | WO1999046232A1 (ja) |
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US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
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JP2007509921A (ja) * | 2003-10-28 | 2007-04-19 | ドクター・レディーズ・ラボラトリーズ・リミテッド | 新規化合物、および薬剤におけるそれらの使用:それらを調製する方法およびそれらを含有する薬学的組成物 |
EA009804B1 (ru) * | 2003-10-31 | 2008-04-28 | Янссен Фармацевтика Н.В. | Производные феноксиуксусных кислот, применимые в качестве двойных агонистов активируемого пероксисомным пролифератором рецептора (ppar) |
PE20050483A1 (es) | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
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PE20060315A1 (es) * | 2004-05-24 | 2006-05-15 | Irm Llc | Compuestos de tiazol como moduladores de ppar |
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US7465804B2 (en) * | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
WO2007033002A1 (en) * | 2005-09-14 | 2007-03-22 | Amgen Inc. | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
FR2892412B1 (fr) * | 2005-10-26 | 2008-05-16 | Galderma Res & Dev | Composes biaromatiques modulateurs des ppars |
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WO2009111004A1 (en) * | 2008-03-04 | 2009-09-11 | Arena Pharmaceuticals, Inc. | Processes for the preparation of intermediates related to the 5-ht2c agonist (r)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine |
WO2009111056A1 (en) * | 2008-03-06 | 2009-09-11 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
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WO2010047674A1 (en) | 2008-10-20 | 2010-04-29 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Low molecular weight thyroid stimulating hormone receptor (tshr) agonists |
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AR074760A1 (es) | 2008-12-18 | 2011-02-09 | Metabolex Inc | Agonistas del receptor gpr120 y usos de los mismos en medicamentos para el tratamiento de diabetes y el sindrome metabolico. |
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US8299117B2 (en) | 2010-06-16 | 2012-10-30 | Metabolex Inc. | GPR120 receptor agonists and uses thereof |
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KR20150070249A (ko) | 2012-10-09 | 2015-06-24 | 아레나 파마슈티칼스, 인크. | 체중 관리 방법 |
KR101569522B1 (ko) | 2013-04-18 | 2015-11-17 | 현대약품 주식회사 | 신규한 3-(4-(벤질옥시)페닐)헥스-4-이노익 산 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
CN113956213A (zh) * | 2021-11-19 | 2022-01-21 | 烟台药物研究所 | 一类2,4-二取代噻唑结构的PPARα/δ双重激动剂及其应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03101669A (ja) * | 1989-06-06 | 1991-04-26 | Roussel Uclaf | 新規なチアゾリルアルコキシアクリル酸エステル、それらの製造法、それらの殺菌剤としての使用及びそれらの製造中間体 |
JPH04217966A (ja) * | 1989-12-20 | 1992-08-07 | Bristol Myers Squibb Co | オキサゾール誘導体 |
JPH09323982A (ja) * | 1996-04-03 | 1997-12-16 | Japan Tobacco Inc | プロピオン酸誘導体及びその用途 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5262540A (en) | 1989-12-20 | 1993-11-16 | Bristol-Myers Squibb Company | [2(4,5-diaryl-2 oxazoyl substituted phenoxy alkanoic acid and esters |
KR20000068151A (ko) | 1996-08-19 | 2000-11-25 | 미즈노 마사루 | 프로피온산 유도체 및 그의 용도 |
-
1999
- 1999-03-09 KR KR1020007010048A patent/KR100620337B1/ko not_active IP Right Cessation
- 1999-03-09 EP EP99939188A patent/EP1067109B1/en not_active Expired - Lifetime
- 1999-03-09 AT AT99939188T patent/ATE451346T1/de not_active IP Right Cessation
- 1999-03-09 AU AU32759/99A patent/AU3275999A/en not_active Abandoned
- 1999-03-09 US US09/623,913 patent/US6506757B1/en not_active Expired - Fee Related
- 1999-03-09 JP JP2000535615A patent/JP4345230B2/ja not_active Expired - Fee Related
- 1999-03-09 DE DE69941777T patent/DE69941777D1/de not_active Expired - Lifetime
- 1999-03-09 WO PCT/JP1999/001134 patent/WO1999046232A1/ja active IP Right Grant
-
2002
- 2002-09-23 US US10/251,805 patent/US7037914B2/en not_active Expired - Fee Related
-
2005
- 2005-07-12 US US11/178,639 patent/US7211591B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03101669A (ja) * | 1989-06-06 | 1991-04-26 | Roussel Uclaf | 新規なチアゾリルアルコキシアクリル酸エステル、それらの製造法、それらの殺菌剤としての使用及びそれらの製造中間体 |
JPH04217966A (ja) * | 1989-12-20 | 1992-08-07 | Bristol Myers Squibb Co | オキサゾール誘導体 |
JPH09323982A (ja) * | 1996-04-03 | 1997-12-16 | Japan Tobacco Inc | プロピオン酸誘導体及びその用途 |
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Publication number | Priority date | Publication date | Assignee | Title |
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WO2001021602A1 (en) * | 1999-09-22 | 2001-03-29 | Bristol-Myers Squibb Company | Oxa- and thiazole derivatives useful as antidiabetic and antiobesity agents |
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US6930120B2 (en) | 2000-08-23 | 2005-08-16 | Eli Lilly And Company | Oxazolyl-arylproplonic acid derivatives and their use as ppar agonists |
US6982278B2 (en) | 2000-08-23 | 2006-01-03 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
US7176224B2 (en) | 2000-08-23 | 2007-02-13 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as PPAR agonists |
US7345070B2 (en) | 2000-08-23 | 2008-03-18 | Eli Lilly And Company | Peroxisome proliferator activated receptor agonists |
US7351728B2 (en) | 2000-08-23 | 2008-04-01 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as PPAR agonists |
WO2002016332A1 (en) * | 2000-08-23 | 2002-02-28 | Eli Lilly And Company | Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists |
WO2002050047A1 (en) * | 2000-12-20 | 2002-06-27 | Glaxo Group Limited | Substitued oxazoles and thiazoles as hppar alpha agonists |
EP1911462A2 (en) | 2001-01-26 | 2008-04-16 | Schering Corporation | Compositions comprising a sterol absorption inhibitor |
US6750236B2 (en) | 2001-05-22 | 2004-06-15 | Bayer Aktiengesellschaft | Propionic acid derivatives |
US6548538B2 (en) | 2001-05-22 | 2003-04-15 | Bayer Aktiengesellschaft | Propionic acid derivatives |
US7282501B2 (en) | 2001-06-07 | 2007-10-16 | Eli Lilly And Company | Modulators of peroxisome proliferator activated receptors (PPAR) |
US6946491B2 (en) * | 2001-06-12 | 2005-09-20 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
US7012071B2 (en) | 2001-06-12 | 2006-03-14 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
US8124625B2 (en) | 2001-09-14 | 2012-02-28 | Shionogi & Co., Ltd. | Method of enhancing the expression of apolipoprotein AI using olefin derivatives |
US8053445B2 (en) | 2001-09-14 | 2011-11-08 | Shionogi & Co., Ltd. | Utilities of olefin derivatives |
JP2005511785A (ja) * | 2001-12-19 | 2005-04-28 | アストラゼネカ アクチボラグ | PPARαの選択的アンタゴニストとしての3−フェニル−2−アリールアルキルチオプロピオン酸誘導体 |
CN100360512C (zh) * | 2001-12-21 | 2008-01-09 | 盖尔德马研究及发展公司 | 联苯基甲基-噻唑烷二酮及其类似物以及它们作为PPAR-γ激活剂的用途 |
US7259175B2 (en) * | 2002-02-25 | 2007-08-21 | Eli Lilly And Company | Peroxisome proliferator activated receptor modulators |
US6939875B2 (en) | 2002-04-05 | 2005-09-06 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
USRE39916E1 (en) | 2002-04-05 | 2007-11-06 | Warner Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
US6875780B2 (en) | 2002-04-05 | 2005-04-05 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
JP2005536480A (ja) * | 2002-05-04 | 2005-12-02 | カン,ヘンジョン | チアゾール誘導体の製造方法及びこれを製造するための中間体 |
WO2003106442A1 (en) * | 2002-05-04 | 2003-12-24 | Heonjoong Kang | Process for preparing thiazole derivative and the intermediate compounds for preparing the same |
US7241901B2 (en) | 2002-05-04 | 2007-07-10 | Heonjoong Kang | Process for preparing thiazole derivative and the intermediate compounds for preparing the same |
JP2006501187A (ja) * | 2002-07-09 | 2006-01-12 | ブリストル−マイヤーズ スクイブ カンパニー | 抗糖尿病薬および抗肥満症薬として有用な置換へテロ環誘導体、並びに方法 |
US6875782B2 (en) | 2002-07-09 | 2005-04-05 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
WO2004004655A3 (en) * | 2002-07-09 | 2004-10-14 | Bristol Myers Squibb Co | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
AU2003248861B2 (en) * | 2002-07-09 | 2009-01-22 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
US7951793B2 (en) | 2002-07-09 | 2011-05-31 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
JP2005538153A (ja) * | 2002-09-05 | 2005-12-15 | ノボ ノルディスク アクティーゼルスカブ | 新規ビニルカルボン酸誘導体およびその治療的使用 |
US7553867B2 (en) | 2002-09-06 | 2009-06-30 | Takeda Pharmaceutical Company Limited | Furan or thiophene derivative and medicinal use thereof |
WO2004022551A1 (ja) * | 2002-09-06 | 2004-03-18 | Takeda Pharmaceutical Company Limited | フランまたはチオフェン誘導体およびその医薬用途 |
JP2006503881A (ja) * | 2002-10-28 | 2006-02-02 | ノボ ノルディスク アクティーゼルスカブ | 新規化合物、その調製および使用 |
JP2006508097A (ja) * | 2002-11-08 | 2006-03-09 | エフ.ホフマン−ラ ロシュ アーゲー | Pparアゴニストとしての置換4−アルコキシオキサゾール誘導体 |
JP2006519198A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 生物学的等価体のカルボン酸基を含むシクロアルキル誘導体、その製造方法、及び医薬としてのその使用 |
JP2006519194A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 2型糖尿病およびアテローム性動脈硬化症の治療のためのpparモジュレーターとしての3−(2−フェニル−オキサゾール−4−イルメトキシ)シクロヘキシルメトキシ酢酸誘導体および関連化合物 |
JP2006519193A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 2型糖尿病およびアテローム性動脈硬化症の治療のためのpparモジュレーターとしての3−メチル−2−(3−(2−フェニル−オキサゾール−4−イルメトキシ)−シクロヘキサンカルボニル−アミノ酪酸誘導体および関連化合物 |
JP2006519199A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 2型糖尿病およびアテローム性動脈硬化症の治療のためのpparモジュレーターとしての4−(3−(2−フェニル−オキサゾール−4−イルメトキシ)−シクロヘキシルオキシ)−ブタン酸誘導体および関連化合物 |
JP2006519195A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 酸性の、主としてヘテロ環式基を含む1,3−置換シクロアルキル誘導体、相当する製造方法、及び医薬としてのその誘導体の使用 |
JP2006519197A (ja) * | 2003-02-27 | 2006-08-24 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ジアリールシクロアルキル誘導体、それらの製造方法、及び医薬としてのそれらの使用 |
US7560475B2 (en) | 2003-09-22 | 2009-07-14 | Ono Pharmaceutical Co., Ltd. | Phenylacetic acid derivative, process for producing the same, and use |
JPWO2005028453A1 (ja) * | 2003-09-22 | 2006-11-30 | 小野薬品工業株式会社 | フェニル酢酸誘導体、その製造方法および用途 |
WO2005028453A1 (ja) | 2003-09-22 | 2005-03-31 | Ono Pharmaceutical Co., Ltd. | フェニル酢酸誘導体、その製造方法および用途 |
JP4661595B2 (ja) * | 2003-09-22 | 2011-03-30 | 小野薬品工業株式会社 | フェニル酢酸誘導体、その製造方法および用途 |
JP2007508270A (ja) * | 2003-10-09 | 2007-04-05 | スミスクライン ビーチャム コーポレーション | I.a.ジスリピデミアの治療におけるhppar作用物質として使用するためのチアゾール−2−カルボキシアミド誘導体 |
EP2305352A1 (en) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | 5-alpha-reductase inhibitors for use in the treatment of men with metabolic and anthropometric disorders |
JP2007532625A (ja) * | 2004-04-13 | 2007-11-15 | セファロン インコーポレイティド | チオ置換アリールメタンスルフィニル誘導体 |
KR100753860B1 (ko) * | 2004-12-31 | 2007-08-31 | 재단법인서울대학교산학협력재단 | 유기 셀레늄 함유 화합물 및 이들 화합물의 용도 |
WO2006071103A1 (en) * | 2004-12-31 | 2006-07-06 | Heonjoong Kang | Organoselenium containing compounds and their use |
US7781469B2 (en) | 2005-05-27 | 2010-08-24 | Shionogi & Co., Ltd. | Arylacetate derivatives having isoxazole skeleton |
WO2006126514A1 (ja) | 2005-05-27 | 2006-11-30 | Shionogi & Co., Ltd. | イソキサゾール骨格を有するアリール酢酸誘導体 |
JP2009507846A (ja) * | 2005-09-07 | 2009-02-26 | プレキシコン,インコーポレーテッド | Ppar活性化合物 |
JP2009509989A (ja) * | 2005-09-29 | 2009-03-12 | サノフィ−アベンティス | フェニル基を有するフェニル−[1,2,4]−オキサジアゾール−5−オン誘導体、その製造方法、及び医薬品としてのその使用 |
JP2010514795A (ja) * | 2006-12-28 | 2010-05-06 | メタボレックス, インコーポレイテッド | 糖尿病および代謝障害を処置するためのヘテロ環式受容体アゴニスト |
US9925189B2 (en) | 2006-12-28 | 2018-03-27 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US9737537B2 (en) | 2006-12-28 | 2017-08-22 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US8975258B2 (en) | 2006-12-28 | 2015-03-10 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
JP2010519306A (ja) * | 2007-02-22 | 2010-06-03 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Gタンパク質共役受容体を調節するための化合物および方法 |
US8846675B2 (en) | 2007-07-19 | 2014-09-30 | Cymabay Therapeutics, Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
JP2011500562A (ja) * | 2007-10-10 | 2011-01-06 | アムジエン・インコーポレーテツド | 置換ビフェニルgpr40調節因子 |
US8815886B2 (en) | 2009-10-01 | 2014-08-26 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US9150567B2 (en) | 2009-10-01 | 2015-10-06 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
WO2012027331A1 (en) | 2010-08-27 | 2012-03-01 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
US9518064B2 (en) | 2012-04-26 | 2016-12-13 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation |
US9688695B2 (en) | 2012-04-26 | 2017-06-27 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation |
US9862730B2 (en) | 2012-04-26 | 2018-01-09 | Bristol-Myers Squibb Company | Imidazothiadiazole derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation |
US10047103B2 (en) | 2012-04-26 | 2018-08-14 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation |
US10428077B2 (en) | 2012-04-26 | 2019-10-01 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor4 (PAR4) inhibitors for treating platelet aggregation |
US10822343B2 (en) | 2012-04-26 | 2020-11-03 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor4 (PAR4) inhibitors for treating platelet aggregation |
US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
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AU3275999A (en) | 1999-09-27 |
US20050250824A1 (en) | 2005-11-10 |
US7037914B2 (en) | 2006-05-02 |
US20030153579A1 (en) | 2003-08-14 |
US6506757B1 (en) | 2003-01-14 |
EP1067109B1 (en) | 2009-12-09 |
KR20010034586A (ko) | 2001-04-25 |
KR100620337B1 (ko) | 2006-09-13 |
EP1067109A4 (en) | 2004-09-22 |
US7211591B2 (en) | 2007-05-01 |
DE69941777D1 (de) | 2010-01-21 |
ATE451346T1 (de) | 2009-12-15 |
EP1067109A1 (en) | 2001-01-10 |
JP4345230B2 (ja) | 2009-10-14 |
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