Amides of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid as zinc-dependent inhibitors of Lp-PLA₂.

Autor: Hu Y; ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA., Lin EC, Pham LM, Cajica J, Amantea CM, Okerberg E, Brown HE, Fraser A, Du L, Kohno Y, Ishiyama J, Kozarich JW, Shreder KR
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Mar 01; Vol. 23 (5), pp. 1553-6. Date of Electronic Publication: 2012 Dec 08.
DOI: 10.1016/j.bmcl.2012.11.048
Abstrakt: AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn(2+)-dependent, 27nM inhibitor of human plasma Lp-PLA(2). Structure-activity relationship studies focused on the AX10479 2-phenylamide group identified equipotent cycloaliphatic amides, an enantioselective preference for chiral amides, and phenyl substitution patterns (e.g., 2-methyl-3-fluoro) that increased potency.
(Copyright © 2012 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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