Synthesis and initial evaluation of novel, non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5

Autor:	Maria L. Webb, Jeffrey J. Letourneau, Michael Ohlmeyer, Hong Li, Biji Jacob, Jinqi Liu, Kenneth C. Appell, Angela Wong, Shalini Bansal, Chris Riviello, Yajing Rong
Rok vydání:	2009
Předmět:	biology Chemistry αv integrins Stereochemistry Organic Chemistry Clinical Biochemistry Integrin Dual inhibitor Pharmaceutical Science Alpha (ethology) Biochemistry Combinatorial chemistry Drug Discovery biology.protein Molecular Medicine Beta (finance) Molecular Biology
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:352-355
ISSN:	0960-894X
Popis:	The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5) is described. High-throughput screening of an extensive series of ECLiPStrade mark compound libraries led to the identification of compound 1 as a dual inhibitor of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5). Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the alpha(v)beta(3) and alpha(v)beta(5) integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ceff62517f977a431d91968ec80e1794 https://doi.org/10.1016/j.bmcl.2008.11.074 Zobrazit plný text záznamu Full Text from ScienceDirect