886585-68-8Relevant articles and documents
Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol- 5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor
Bhide, Rajeev S.,Cai, Zhen-Wei,Zhang, Yong-Zheng,Qian, Ligang,Wei, Donna,Barbosa, Stephanie,Lombarde, Louis J.,Borzilleri, Robert M.,Zheng, Xiaoping,Wu, Laurence I.,Barrish, Joel C.,Kim, Soong-Hoon,Leavitt, Kenneth,Mathur, Arvind,Leith, Leslie,Chao, Sam,Wautlet, Barri,Mortillo, Steven,Jeyaseelan Sr., Robert,Kukral, Daniel,Hunt, John T.,Kamath, Amrita,Fura, Aberra,Vyas, Viral,Marathe, Punit,D'Arienzo, Celia,Derbin, George,Fargnoli, Joseph
, p. 2143 - 2146 (2006)
A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo-[2.1-f][1,2,4] triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a substituted alkoxy group at the 6-position of the pyrrolo[2,1-f][1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12), which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The L-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.
