31785-06-5Relevant academic research and scientific papers
Discovery of a Pyrimidothiazolodiazepinone as a Potent and Selective Focal Adhesion Kinase (FAK) Inhibitor
Groendyke, Brian J.,Nabet, Behnam,Mohardt, Mikaela L.,Zhang, Haisheng,Peng, Ke,Koide, Eriko,Coffey, Calvin R.,Che, Jianwei,Scott, David A.,Bass, Adam J.,Gray, Nathanael S.
supporting information, p. 30 - 38 (2021/01/11)
Focal adhesion kinase (FAK) is a tyrosine kinase with prominent roles in protein scaffolding, migration, angiogenesis, and anchorage-independent cell survival and is an attractive target for the development of cancer therapeutics. However, current FAK inhibitors display dual kinase inhibition and/or significant activity on several kinases. Although multitargeted activity is at times therapeutically advantageous, such behavior can also lead to toxicity and confound chemical-biology studies. We report a novel series of small molecules based on a tricyclic pyrimidothiazolodiazepinone core that displays both high potency and selectivity for FAK. Structure-activity relationship (SAR) studies explored modifications to the thiazole, diazepinone, and aniline "tail,"which identified lead compound BJG-03-025. BJG-03-025 displays potent biochemical FAK inhibition (IC50 = 20 nM), excellent kinome selectivity, activity in 3D-culture breast and gastric cancer models, and favorable pharmacokinetic properties in mice. BJG-03-025 is a valuable chemical probe for evaluation of FAK-dependent biology.
SMALL-MOLECULE FOCAL ADHESION KINASE (FAK) INHIBITORS
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Paragraph 00204; 00206, (2020/11/30)
Disclosed are compounds that possess inhibitory activity against FAK. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat cancer mediated by aberrant FAK activity.
A Strecker approach to 2-substituted ethyl 5-aminothiazole-4-carboxylates
Cheng, Ken,McClory, Andrew,Walker, Whitney,Xu, Jie,Zhang, Haiming,Angelaud, Remy,Gosselin, Francis
supporting information, p. 1736 - 1738 (2016/04/05)
A general approach to 2-substituted ethyl 5-aminothiazole-4-carboxylates is reported herein. Both aliphatic and aromatic thioamides undergo 1,2-addition to ethyl glyoxylate to give hemiaminals which, when treated with acetyl chloride, undergo elimination
CYCLIC ETHER PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
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, (2014/04/03)
Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein R2 is a cyclic ether and X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
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, (2013/04/10)
Pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
4-SUBSTITUTED PYRIDIN-3-YL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
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, (2011/04/18)
The invention relates to compounds of formula (I) which are useful as kinase inhibitors, more specifically useful as PIM kinase inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same, either alone or in combination, to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
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, (2011/10/19)
Pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein X is a thiazolyl, picolinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
REACTION OF ACYLAMINOCYANOESTERS WITH 2,4-BIS(4-METHOXYPHENYL)-1,3,2,4-DITHIADIPHOSPHETANE 2,4-DISULFIDE LEADING TO SUBSTITUTED AMINOTHIAZOLES. CRYSTAL STRUCTURE OF 5-AMINOTHIAZOLE-4-CARBOXYLIC ACID ETHYL ESTER.
Golankiewicz, Bozenna,Januszczyk, Piotr,Gdaniec, Maria,Kosturkiewicz, Zofia
, p. 5989 - 5994 (2007/10/02)
2-Acylamino-2-cyanoacetic acid ethyl esters 2a-c react with 2.4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide 1 in refluxing benzene with formation of 2-alkyl(aryl)-5-aminothiazole-4-carboxylic acid ethyl esters 3a-c.Structure 3 was estab
