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)

Autor:	Zhen-wei, Cai, Yongzheng, Zhang, Robert M, Borzilleri, Ligang, Qian, Stephanie, Barbosa, Donna, Wei, Xiaoping, Zheng, Lawrence, Wu, Junying, Fan, Zhongping, Shi, Barri S, Wautlet, Steve, Mortillo, Robert, Jeyaseelan, Daniel W, Kukral, Amrita, 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
Rok vydání:	2008
Předmět:	Lung Neoplasms Drug Evaluation Preclinical Administration Oral Biological Availability Mice Clinical Trials Phase II as Topic Microsomes Animals Humans Prodrugs Pyrroles Receptor Fibroblast Growth Factor Type 1 Protein Kinase Inhibitors Cell Proliferation Alanine Molecular Structure Triazines Carcinoma Water Stereoisomerism Vascular Endothelial Growth Factor Receptor-2 Xenograft Model Antitumor Assays Intestines Liver Solubility Drug Design
Zdroj:	Journal of medicinal chemistry. 51(6)
ISSN:	0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::0b495017795e0a7d90b32a768d5d70dc https://pubmed.ncbi.nlm.nih.gov/18288793 Zobrazit plný text záznamu