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

AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn2+-dependent, 27nM inhibitor of human plasma Lp-PLA2. Structure–activity relationship studies focused on the AX10479 2-phenylamide group identified equipotent cycloaliphatic amides, an en...

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Published inBioorganic & medicinal chemistry letters Vol. 23; no. 5; pp. 1553 - 1556
Main Authors Hu, Yi, Lin, Emme C.K., Pham, Lan M., Cajica, Julia, Amantea, Christopher M., Okerberg, Eric, Brown, Heidi E., Fraser, Allister, Du, Lingling, Kohno, Yasushi, Ishiyama, Junichi, Kozarich, John W., Shreder, Kevin R.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 01.03.2013
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Summary:AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn2+-dependent, 27nM inhibitor of human plasma Lp-PLA2. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.11.048