Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1 H-indol-5-yloxy)-5-methylpyrrolo [2, 1-f][1, 2, 4] triazin-6-yloxy) propan-2-yl) 2-aminopropanoate), a …

…, BS Wautlet, S Mortillo, R Jeyaseelan Sr…

Index: Cai, Zhen-Wei; Zhang, Yongzheng; Borzilleri, Robert M.; Qian, Ligang; Barbosa, Stephanie; Wei, Donna; Zheng, Xiaoping; Wu, Lawrence; Fan, Junying; Shi, Zhongping; Wautlet, Barri S.; Mortillo, Steve; Jeyaseelan Sr., Robert; Kukral, Daniel W.; Kamath, Amrita; Marathe, Punit; D'Arienzo, Celia; Derbin, George; Barrish, Joel C.; Robl, Jeffrey A.; Hunt, John T.; Lombardo, Louis J.; Fargnoli, Joseph; Bhide, Rajeev S. Journal of Medicinal Chemistry, 2008 , vol. 51, # 6 p. 1976 - 1980

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Citation Number: 117

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 ...