title: Pyrazole-based sulfonamide and sulfamides as potent inhibitors of mammalian 15-lipoxygenase.
abstract: A series of inhibitors of mammalian 15-lipoxygenase (15-LO) based on a 3,4,5-tri-substituted pyrazole scaffold is described. Replacement of a sulfonamide functionality in the lead series with a sulfamide group resulted in improved physicochemical properties generating analogs with enhanced inhibition in cell-based and whole blood assays.
authors.affiliation: Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, USA. khehyong.ngu@bms.com
authors.forename: Khehyong
authors.initials: K
authors.lastname: Ngu
authors.forename: David S
authors.initials: DS
authors.lastname: Weinstein
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
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: Xing
authors.initials: X
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: Saleem
authors.initials: S
authors.lastname: Ahmad
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; C031280:pyrazole; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase