31785-06-5Relevant articles and documents
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.
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
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.
