Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor

  • Bioorg Med Chem Lett. 2008 May 1;18(9):2985-9. doi: 10.1016/j.bmcl.2008.03.057.
Réjean Ruel  1 ,  Carl Thibeault ,  Alexandre L'Heureux ,  Alain Martel ,  Zhen-Wei Cai ,  Donna Wei ,  Ligang Qian ,  Joel C Barrish ,  Arvind Mathur ,  Celia D'Arienzo ,  John T Hunt ,  Amrita Kamath ,  Punit Marathe ,  Yueping Zhang ,  George Derbin ,  Barri Wautlet ,  Steven Mortillo ,  Robert Jeyaseelan Sr ,  Benjamin Henley ,  Ravindra Tejwani ,  Rajeev S Bhide ,  George L Trainor ,  Joseph Fargnoli ,  Louis J Lombardo
Affiliations
  • 1. Bristol-Myers Squibb, Research and Development, Candiac, Que., Canada J5R 1J1. [email protected]
PMID: 18395443 DOI: 10.1016/j.bmcl.2008.03.057
Abstract

We report herein a series of substituted N-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amines as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. Through structure-activity relationship studies, biochemical potency, pharmacokinetics, and kinase selectivity were optimized to afford BMS-645737 (13), a compound with good preclinical in vivo activity against human tumor xenograft models.

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