913067-90-0Relevant articles and documents
1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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, (2015/12/30)
The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: Design, synthesis, and biological evaluation
Huang, Wei-Sheng,Zhu, Xiaotian,Wang, Yihan,Azam, Mohammad,Wen, David,Sundaramoorthi, Raji,Thomas, R. Mathew,Liu, Shuangying,Banda, Geetha,Lentini, Scott P.,Das, Sasmita,Xu, Qihong,Keats, Jeff,Wang, Frank,Wardwell, Scott,Ning, Yaoyu,Snodgrass, Joseph T.,Broudy, Marc I.,Russian, Karin,Daley, George Q.,Iuliucci, John,Dalgarno, David C.,Clackson, Tim,Sawyer, Tomi K.,Shakespeare, William C.
experimental part, p. 4743 - 4756 (2010/03/03)
A novel series of potent dual Src/Abl kinase inhibitors based on a 9-(arenethenyl)purine core has been identified. Unlike traditional dual Src/Abl inhibitors targeting the active enzyme conformation, these inhibitors bind to the inactive, DFG-out conformation of both kinases. Extensive SAR studies led to the discovery of potent and orally bioavailable inhibitors, some of which demonstrated in vivo efficacy. Once-daily oral administration of inhibitor 9i (AP24226) significantly prolonged the survival of mice injected intravenously with wild type Bcr-Abl expressing Ba/F3 cells at a dose of 10 mg/kg. In a separate model, oral administration of 9i to mice bearing subcutaneous xenografts of Src Y527F expressing NIH 3T3 cells elicited dose-dependent tumor shrinkage with complete tumor regression observed at the highest dose. Notably, several inhibitors (e.g., 14a, AP24163) exhibited modest cellular potency (IC50 = 300-400 nM) against the Bcr-Abl mutant T315I, a variant resistant to all currently marketed therapies for chronic myeloid leukemia. 2009 American Chemical Society.
UNSATURATED HETEROCYCLIC DERIVATIVES
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Page/Page column 36, (2008/06/13)
This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.
