Discovery of Brivanib Alaninate ((S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), A Novel Prodrug of Dual Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1 Kinase Inhibitor (BMS-540215)
Journal of Medicinal Chemistry2008Vol. 51(6), pp. 1976–1980
Citations Over TimeTop 10% of 2008 papers
Zhen‐Wei Cai, Yongzheng Zhang, R. M. Borzilleri, Ligang Qian, Stephanie A. Barbosa, Donna Wei, Xiaoping Zheng, Lawrence Wu, Junying Fan, Zhongping Shi, Barri Wautlet, Steve Mortillo, Robert Jeyaseelan, Daniel Kukral, Amrita V. Kamath, Punit Marathe, Celia D’Arienzo, George Derbin, Joel C. Barrish, Jeffrey A. Robl, John T. Hunt, Louis J. Lombardo, Joseph Fargnoli, Rajeev S. Bhide
Abstract
A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.
Related Papers
- → Oral bioavailability of 17 β-estradiol and prodrugs tested in rats, pigs and dogs(1996)8 cited
- → Synthesis and relative bioavailability of meptazinol benzoyl esters as prodrugs(2005)3 cited
- → Actin Organization as an in Vitro Assay for Tumorigenicity(1982)2 cited
- Prodrug Decision of Novel Genistein Sulfonate and Its Bioavailability in Rats(2012)
- Pre-clinical pharmacokinetics of novel soybean iosflavone sulfonate(2012)