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Design and Optimization of a Series of 1-Sulfonylpyrazolo[4,3-b]pyridines as Selective c-Met Inhibitors.
- Source :
-
Journal of Medicinal Chemistry . Mar2015, Vol. 58 Issue 5, p2513-2529. 17p. - Publication Year :
- 2015
-
Abstract
- c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of p-p stacking interactions and solvent accessible polar moieties led to a series of highly potent and selective type I c-Met inhibitors. On the basis of in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00222623
- Volume :
- 58
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 101625480
- Full Text :
- https://doi.org/10.1021/jm502018y