title: Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: highly potent against human enzyme within a cellular environment.
abstract: A series of 2,4,5-tri-substituted imidazoles has proven to be highly potent in inhibiting mammalian 15-lipoxygenase (15-LO) with excellent selectivity over human isozymes 5- and P-12-LO. Non-symmetrical sulfamides (e.g., 21a-n) were found to be suitable replacements for the earlier arylsulfonamide-containing members of this series (e.g., 2, 14a-p). Several members of these series also demonstrated potent inhibition of human 15-LO in a cell-based assay.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, PO Box 4000, Princeton, NJ 08543-5400, USA. david.weinstein@bms.com
authors.forename: David S
authors.initials: DS
authors.lastname: Weinstein
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Khehyong
authors.initials: K
authors.lastname: Ngu
authors.forename: Charles
authors.initials: C
authors.lastname: Langevine
authors.forename: Donald W
authors.initials: DW
authors.lastname: Combs
authors.forename: Shaobin
authors.initials: S
authors.lastname: Zhuang
authors.forename: Cindy
authors.initials: C
authors.lastname: Chen
authors.forename: Cort S
authors.initials: CS
authors.lastname: Madsen
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Harper
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007093:Imidazoles; D016859:Lipoxygenase Inhibitors