title: Amides of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid as zinc-dependent inhibitors of Lp-PLA₂.
abstract: 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.
authors: ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Yi
authors: Y
authors: Hu
authors: Emme C K
authors: EC
authors: Lin
authors: Lan M
authors: LM
authors: Pham
authors: Julia
authors: J
authors: Cajica
authors: Christopher M
authors: CM
authors: Amantea
authors: Eric
authors: E
authors: Okerberg
authors: Heidi E
authors: HE
authors: Brown
authors: Allister
authors: A
authors: Fraser
authors: Lingling
authors: L
authors: Du
authors: Yasushi
authors: Y
authors: Kohno
authors: Junichi
authors: J
authors: Ishiyama
authors: John W
authors: JW
authors: Kozarich
authors: Kevin R
authors: KR
authors: Shreder
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: D000577:Amides; D011804:Quinolines; C059924:quinoline-4-carboxylic acid; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D015032:Zinc