CN103772317B - 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes - Google Patents
2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes Download PDFInfo
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- CN103772317B CN103772317B CN201410003840.3A CN201410003840A CN103772317B CN 103772317 B CN103772317 B CN 103772317B CN 201410003840 A CN201410003840 A CN 201410003840A CN 103772317 B CN103772317 B CN 103772317B
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- methoxyl group
- sulfonamido
- benzothiazolyl
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- acetylaminohydroxyphenylarsonic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms
Abstract
The invention discloses a kind of 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes.2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, it is characterized in that, the structural formula of this compounds is:
in formula, R is alkyl or aryl.This compounds have significantly external, anti-tumor in vivo is active, has the purposes preparing anti-tumor medicinal preparation.
Description
Technical field
The invention belongs to antitumor drug technical field, relate to 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes.
Background technology
Malignant tumour serious threat human health.Over nearly 20 years, the M & M of China's malignant tumour constantly rises, and the sickness rate of some tumour is up to 2,00/,100,000 people, and annual new cases reach 3,500,000, and death, more than 2,000,000, is controlling more than patient 6,000,000 people.
The treatment means of current tumour remains traditional operative treatment, radiotherapy and pharmacological agent, but is still based on pharmacological agent to a great extent.In recent years, along with the progress of molecular biology, RESEARCH ON CELL-BIOLOGY, more deep understanding has been had to tumorigenic Biological Mechanism, have found the novel targets of many antitumor drug effects, the exploitation of antitumor drug is made to obtain many achievements newly, as topoisomerase enzyme inhibitor, kinases inhibitor, PI3K inhibitor, mTOR inhibitors etc.
In most tumors cell, some kinases present high expression level or excessive activation.For this feature, the kinase whose antitumor drugs of target such as Gefitinib, imatinib, erlotinib, Conmana, Xarelto, Sutent and lapatinibditosylate are developed.But in clinical rear discovery, it is not efficient high in some medicinal application, and some medicine acting on single target spot easily produces resistance.Therefore, research and develop new antitumor drug or act on the antitumor drug of multiple target spot simultaneously significant.
Document J.Med.Chem.2011,54,1789 – 1811 report that compound 2-acetylaminohydroxyphenylarsonic acid 6-[2-chloro-3-(4-fluorophenyl sulfonamido)-5-pyridyl] benzothiazole has the activity well suppressing kinases PI3K and mTOR, experimentation on animals proves to have obvious antitumor action, but, such toxicity of compound is comparatively large, and 3mg/kg can cause Mouse Weight obviously to decline.
Summary of the invention
The object of the invention is to provide a kind of 2-methoxyl group-3-and replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and preparation method thereof and purposes, the fragment of the present invention's benzoyl instead of document J.Med.Chem.2011,54, in 1789 – 1811 report 2-acetylaminohydroxyphenylarsonic acid 6-[2-chloro-3-(4-fluorophenyl sulfonamido)-5-pyridyl] benzothiazole in pyridine fragment, obtain 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound.This compounds has obvious anti-tumor activity, and toxicity reduces greatly, and its synthesis material is easy to get, synthetic method easily realizes, and can be applicable to the preparation of antitumor drug.
The present invention is achieved through the following technical solutions:
2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, it is characterized in that, the structural formula of this compounds is:
In formula, R is alkyl or aryl.
Described alkyl is cyclopropyl, cyclohexyl, propyl group.
Described aryl is 4-fluorophenyl, 4-aminomethyl phenyl, 4-chloro-phenyl-, 2,4 difluorobenzene base.
A kind of 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) preparation method of benzamide compound, it is characterized in that, comprise the following steps:
Midbody compound A and midbody compound B carries out suzuki reaction and obtains 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound (I), its reaction formula is as follows:
In formula, in compd A, R is cyclopropyl, cyclohexyl, propyl group, 4-fluorophenyl, 4-aminomethyl phenyl, 4-chloro-phenyl-, 2,4 difluorobenzene base.
Adopt suzuki reaction, at PdCl
2(dppf) under catalysis, compd A, compd B are mixed in a solvent with an alkali metal salt, stirring and refluxing 1 ~ 5h under nitrogen protection, steam solvent, be separated from reaction mixture and obtain 2-methoxyl group-3-replacement sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound;
Described compd A is 2-methoxyl group-3-propylsulfonamido-5-brombenzamide, 2-methoxyl group-3-cyclopropyl sulfonyl amino-5-brombenzamide, 2-methoxyl group-3-cyclohexylsulfonyl amino-5-brombenzamide, 2-methoxyl group-3-(4-fluorophenyl sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(4-methylphenyl-sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(4-chloro-phenyl-sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(2,4-difluorophenyl sulfonamido)-5-brombenzamide;
Described compd B is 2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl pinacol borate;
Described solvent is one or more in tetrahydrofuran (THF), dioxane, glycol dimethyl ether, dimethyl formamide, water.
Described an alkali metal salt is sodium carbonate, salt of wormwood, cesium carbonate or sodium-acetate, and the mol ratio of itself and compd A is 1:1 ~ 5:1;
Described compd A and the mol ratio of compd B are 1:1; The compd A of 1 mole joins in the solvent of 5 ~ 10L and reacts; Catalyst P dCl
2(dppf) be the 5%-20% of compd A molar weight.
Described 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound preparing the application in antitumor drug.
2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamides adds auxiliary material and makes tablet, capsule or injection, the 2-methoxyl group-3-wherein containing 10 ~ 500mg in every sheet or grain or a preparation replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound.
Described auxiliary material comprises one or more in additive, stablizer, solubilizing agent, lubricant, disintegrating agent.
Compared with prior art, the present invention has following useful technique effect:
1. novel structure.2-methoxyl group-3-provided by the invention replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound has no bibliographical information.The structure fragment of the present invention's benzamide instead of the structure fragment of pyridine ring, can obtain new antineoplastic compound.This compounds and J.Med.Chem.2011, compound 2-acetylaminohydroxyphenylarsonic acid 6-[2-chloro-3-(4-fluorophenyl the sulfonamido)-5-pyridyl] benzothiazole that 54,1789 – 1811 report has similar pharmacophore, also has anti-tumor activity.
2. there is obvious anti-tumor activity.Antitumor test in external, body all proves, compound provided by the invention has obvious anti-tumor activity.As compound 2-methoxyl group-3-(4-fluorobenzene sulfonamido)-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide (in table 1 compound 4) suppresses the IC of human breast cancer cell line Bcap-37
50be 0.50 μm of ol/L.Patent " 2; 3,5-trisubstituted benzene Carbox amide and its production and use " (application number: the compound 2-methoxyl group-3-(4-fluorobenzene sulfonamido 201210224812.5) reported)-5-(2-cyclopropylcarboxamido-6-benzothiazolyl) benzamide suppresses the IC of human breast cancer cell line Bcap-37
50be 3.34 μm of ol/L.Anti-mouse S-180 knurl in body, dosage is 30mg/kg, and the former tumour inhibiting rate is 80%, and the latter's tumour inhibiting rate is 45%.
3. synthesis material inexpensive, be easy to get.Compared with pyridine derivate, benzamide derivatives is inexpensive, be easy to get; Compared with Cyclopropyl carbonyl chloride, Acetyl Chloride 98Min. is inexpensive, be easy to get.
4. toxicity is little.J.Med.Chem.2011,54,1789 – 1811 report that active best compound is to mouse stomach administration 1 time, and 15mg/kg can cause dead mouse.Compound provided by the invention is to mouse stomach administration 1 time, and 400mg/kg does not cause dead mouse.
Accompanying drawing explanation
Fig. 1 is that 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound is to the half-inhibition concentration contrast histogram of human breast cancer cell line Bcap-37.
Fig. 2 is the tumor growth restraining effect of compound 4 couples of mouse S-180.
Embodiment
The invention provides 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound and its production and use, the structure fragment of the present invention's benzamide instead of the structure fragment of pyridine ring, can obtain new antineoplastic compound.Below this compound is further described.It should be noted that, following examples are used for explanation of the present invention and unrestricted the present invention.Although by preferred embodiment to invention has been detailed description, those of ordinary skill in the art should be appreciated that and can to modify to the present invention under not departing from the scope of the present invention, be out of shape or equivalently replace, and all belongs to protection scope of the present invention.
One class 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, the structural formula of this compounds is:
Wherein, R is alkyl or aryl.
Described alkyl is cyclopropyl, cyclohexyl, propyl group.
Described aryl is 4-fluorophenyl, 4-aminomethyl phenyl, 4-chloro-phenyl-, 2,4 difluorobenzene base.
Provide some representative compound numbering, structure and HRMS data (structure of target compound is determined through high resolution mass spectrum HRMS) below, specifically as shown in table 1.
Some concrete compound number of table 1., structure and HRMS data
The synthetic method of above-claimed cpd is:
Carry out suzuki reaction with compd A and compd B to obtain 2-methoxyl group-3-and replace sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, its reaction formula is as follows:
In formula I, in compd A, R is cyclopropyl, cyclohexyl, propyl group, 4-fluorophenyl, 4-aminomethyl phenyl, 4-chloro-phenyl-, 2,4 difluorobenzene base.
Provide the synthetic example of above-claimed cpd below.
Embodiment 1
2-methoxyl group-3-cyclopropyl sulfonyl amino-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (1)
Compd A: the preparation of 2-methoxyl group-3-cyclopropyl sulfonyl amino-5-brombenzamide (A)
Compound 2-methoxyl group-3-amino-5-brombenzamide (11g, 45mmol) is dissolved in pyridine (120mL), is cooled to 0 DEG C, add corresponding SULPHURYL CHLORIDE (50mmol) in batches, mixture and stirring at room temperature 12h, decompression removing pyridine, adds water (200mL) in residue, leave standstill, suction filtration, solid washed with water, dry, obtain compd A, yield 82-92%.
Compd B: the preparation of 2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl pinacol borate (B)
Reference J.Med.Chem.2011, prepared by 54,1789 – 1811.
2-methoxyl group-3-cyclopropyl sulfonyl amino-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (1)
Compd A is added namely: 2-methoxyl group-3-cyclopropyl sulfonyl amino-5-brombenzamide (A, 0.3g), compd B (0.5g), PdCl in 100mL round-bottomed flask
2(dppf) (40mg), sodium carbonate (0.3g), water (6mL) and glycol dimethyl ether (12mL), mixture is stirring and refluxing 3h under nitrogen protection, steams solvent, and resistates silica gel column chromatography is separated (chloroform: methyl alcohol=30:1) and obtains product 0.3g.
Embodiment 2
2-methoxyl group-3-propylsulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (2)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-propylsulfonamido-5-brombenzamide replaces 2-methoxyl group-3-cyclopropyl sulfonyl amino-5-brombenzamide; Glycol dimethyl ether is replaced with dioxane.
Embodiment 3
2-methoxyl group-3-cyclohexylsulfonyl amino-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (3)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-cyclohexylsulfonyl amino-5-brombenzamide replaces 2-methoxyl group-3-ring third sulfonamido-5-brombenzamide; Glycol dimethyl ether is replaced with tetrahydrofuran (THF).Sodium carbonate is replaced with salt of wormwood.
Embodiment 4
2-methoxyl group-3-(4-fluorophenyl sulfonamido)-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (4)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-(4-fluorophenyl sulfonamido)-5-brombenzamide replacement 2-methoxyl group-3-ring third sulfonamido-5-brombenzamide; Glycol dimethyl ether is replaced with dimethyl formamide.
Embodiment 5
2-methoxyl group-3-(4-fluorophenyl sulfonamido)-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (5)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-(4-methylphenyl-sulfonamido)-5-brombenzamide replacement 2-methoxyl group-3-ring third sulfonamido-5-brombenzamide; Glycol dimethyl ether is replaced with dimethyl formamide.
Embodiment 6
2-methoxyl group-3-(4-chloro-phenyl-sulfonamido)-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (6)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-(4-chloro-phenyl-sulfonamido)-5-brombenzamide replacement 2-methoxyl group-3-ring third sulfonamido-5-brombenzamide; Sodium carbonate is replaced with cesium carbonate.
Embodiment 7
2-methoxyl group-3-(2,4-difluorophenyl sulfonamido)-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) synthesis of benzamide (7)
With the synthesis of compound 1.Compd A 2-methoxyl group-3-(2,4-difluorophenyl sulfonamido)-5-brombenzamide replacement 2-methoxyl group-3-ring third sulfonamido-5-brombenzamide; Glycol dimethyl ether is replaced with dimethyl formamide.
Sodium carbonate in above-described embodiment or cesium carbonate are an alkali metal salt, and they can also replace with salt of wormwood or sodium-acetate, and the mol ratio of itself and compd A is within the scope of 1:1 ~ 5:1; Catalyst P dCl
2(dppf) be compd A molar weight 5%-20% within the scope of.Involved chemical reagent market of the present invention all can be buied.
2-methoxyl group-3-provided by the invention replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, can be used in preparing anti-tumor medicinal preparation, wherein in every sheet or grain or this pharmaceutical preparation containing 10-500mg.When the active compound provided utilizing the present invention prepares anti-tumor medicinal preparation, this medicine can be made tablet, capsule or injection.These pharmaceutical preparations can be made according to the conventional fabrication process of various preparation.For tablet or capsule, preferred content is 20-150mg.And can pharmaceutical excipient be contained in the oral preparations that the present invention relates to, comprise additive, stablizer, solubilizing agent, lubricant, disintegrating agent etc., as starch, dextrin, glucose, lactose, Mierocrystalline cellulose, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, pectin, cyclodextrin, twen-80, polyvinyl alcohol, Magnesium Stearate, talcum powder etc.
The checking of anti-tumor activity
In order to verify that 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) anti-tumor activity of benzamide compound, be specifically positive control medicine with BEZ235, adopt external mtt assay to determine the growth-inhibiting effect of compound 1-7 to human breast cancer cell line Bcap-37.
Verification method: tumour cell A549 is cultivated containing in the RPMI1640 substratum of 10% calf serum, includes mould and have 100UmL
-1, Streptomycin sulphate 100 μ gmL
-1, in 37 DEG C, 5%CO
2secondary Culture in incubator.Get the tumour cell that 0.3% trysinization is adherent, containing the RPMI1640 nutrient solution preparation cell suspension of 10% calf serum, concentration is 6 × 10
3individual cells/ml.In 96 well culture plates, 200 μ L(are inoculated about containing 1000 tumour cells in every hole), cultivate 24h for 37 DEG C.Administration group adds different concns medicine, every medicine setting 10
-4, 10
-5, 10
-6, 10
-7, 10
-8molL
-15 concentration, often group establishes 5 parallel holes.Control group adds isopyknic solvent with medicine, is placed in 37 DEG C, 5%CO
2discard nutrient solution after cultivating 72h in incubator, every hole adds 20 μ l5mgmL
-1mTT solution, after hatching 4h, abandoning supernatant, every hole adds DMSO150 μ L, measures optical density value (OD) after gentle agitation by microplate reader under 570nm.Result calculates:
With the tumour cell of solvent control process for control group, ask the inhibiting rate of drug on tumor cell according to the following formula.
And adopt linear regression method calculation of half inhibitory concentration (IC further
50).
IC
50measurement result as shown in Figure 1, can see that the growth of all compounds to MCF-7 has obvious restraining effect, the wherein IC of some compound
50value is suitable with BEZ235, the especially IC of compound 4
50=0.50 μm of ol/L; The IC of positive drug BEZ235
50=0.55 μm of ol/L, effect is suitable with BEZ235.
The checking of anti-tumor in vivo activity
S-180 tumor-bearing mice 24, is divided into 3 groups, i.e. group of solvents at random, compound 410mg/kg group and 30mg/kg.Compound 4 NMP, PEG400 and water dissolution.Administration group mouse gastric infusion every day once, successive administration 8 days.Group of solvents mouse gavage every day solvent (20mL/kg) once.9th day, put to death mouse, peel off knurl block, weigh, compare with group of solvents, the results are shown in Figure 2.Illustrate that administration group tumor growth is subject to obvious suppression.
Acute toxicity test
Compound 4 NMP, PEG400 and water dissolution, with different dosage, to the disposable gastric infusion of mouse, observe 7 days, determine the minimum dose causing dead mouse.Result shows: 2-acetylaminohydroxyphenylarsonic acid 6-[2-chloro-3-(4-fluorophenyl sulfonamido)-5-pyridyl] benzothiazole administration 15mg/kg causes dead mouse; And compound 4 administration 400mg/kg mouse in the present invention is movable normal.Illustrate that toxicity of compound provided by the invention is very little.
The part that the present embodiment does not describe in detail and english abbreviation belong to the common practise of the industry, can search on the net, do not describe one by one here.
Claims (4)
1. 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound, it is characterized in that, the structural formula of this compounds is:
In formula, R is 4-fluorine, 2,4-difluoros, 4-chlorine or 4-methyl.
2. 2-methoxyl group-3-replaces sulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) preparation method of benzamide compound, it is characterized in that, comprise the following steps:
Midbody compound A and midbody compound B carries out suzuki reaction and obtains 2-methoxyl group-3-phenylsulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound (I), its reaction formula is as follows:
In formula, in compd A, R is 4-fluorine, 2,4-difluoros, 4-chlorine, 4-methyl.
3. 2-methoxyl group-3-phenylsulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl as claimed in claim 2) preparation method of benzamide compound, it is characterized in that, adopt suzuki reaction, at PdCl
2(dppf) under catalysis, compd A, compd B are mixed in a solvent with an alkali metal salt, stirring and refluxing 1 ~ 5h under nitrogen protection, steam solvent, be separated from reaction mixture and obtain 2-methoxyl group-3-phenylsulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl) benzamide compound;
Described compd A is 2-methoxyl group-3-(4-fluorophenyl sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(4-methylphenyl-sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(4-chloro-phenyl-sulfonamido)-5-brombenzamide, 2-methoxyl group-3-(2,4-difluorophenyl sulfonamido)-5-brombenzamide;
Described compd B is 2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl pinacol borate;
Described solvent is one or more in tetrahydrofuran (THF), dioxane, glycol dimethyl ether, dimethyl formamide, water.
4. 2-methoxyl group-3-phenylsulfonamido-5-(2-acetylaminohydroxyphenylarsonic acid 6-benzothiazolyl as claimed in claim 3) preparation method of benzamides, it is characterized in that, described an alkali metal salt is sodium carbonate, salt of wormwood, cesium carbonate or sodium-acetate, and the mol ratio of itself and compd A is 1:1 ~ 5:1;
Described compd A and the mol ratio of compd B are 1:1; The compd A of 1 mole joins in the solvent of 5 ~ 10L and reacts; Catalyst P dCl
2(dppf) be the 5%-20% of compd A molar weight.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2716947A1 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Imidazo [4,5-b] pyridine derivatives used as raf inhibitors |
| CN102746241A (en) * | 2012-07-02 | 2012-10-24 | 西安交通大学 | 2, 3, 5-trisubstituted benzamide compound, and preparation method and application thereof |
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| WO2009114874A2 (en) * | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2716947A1 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Imidazo [4,5-b] pyridine derivatives used as raf inhibitors |
| CN102746241A (en) * | 2012-07-02 | 2012-10-24 | 西安交通大学 | 2, 3, 5-trisubstituted benzamide compound, and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors;Noel D. D’Amico et al.;《J. Med. Chem.》;20110118;第54卷;1789-1811 * |
| Molecular simulation of a series of benzothiazole PI3Kα inhibitors: probing the relationship between structural features, anti-tumor potency and selectivity;Jinan Wang et al.;《J. Mol. Model》;20111203;第18卷;2943-2958 * |
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