title: N-(5-substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5-lipoxygenase.
abstract: Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20-100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL) whole cell assays. Compound 4k also showed significant anti-inflammatory activity in the adjuvant arthritic rat at an oral dose of 3 mg/kg.
authors.affiliation: R. W. Johnson Pharmaceutical Research Institute, Raritan NJ 08869, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Beers
authors.forename: E A
authors.initials: EA
authors.lastname: Malloy
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Wachter
authors.forename: J
authors.initials: J
authors.lastname: Ansell
authors.forename: M
authors.initials: M
authors.lastname: Singer
authors.forename: M
authors.initials: M
authors.lastname: Steber
authors.forename: A
authors.initials: A
authors.lastname: Barbone
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: D
authors.initials: D
authors.lastname: Ritchie
authors.forename: D
authors.initials: D
authors.lastname: Argentieri
mesh_terms: D000284:Administration, Oral; D000478:Alkylation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000138:chemical synthesis; D006801:Humans; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000893:Anti-Inflammatory Agents; D004987:Ethers; D016859:Lipoxygenase Inhibitors; D013440:Sulfides; D013449:Sulfonamides; D013876:Thiophenes