N-(5-substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5-lipoxygenase.
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.
Beers
S A
SA
R. W. Johnson Pharmaceutical Research Institute, Raritan NJ 08869, USA.
Malloy
E A
EA
Wu
W
W
Wachter
M
M
Ansell
J
J
Singer
M
M
Steber
M
M
Barbone
A
A
Kirchner
T
T
Ritchie
D
D
Argentieri
D
D
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
D000893:Anti-Inflammatory Agents; D004987:Ethers; D016859:Lipoxygenase Inhibitors; D013440:Sulfides; D013449:Sulfonamides; D013876:Thiophenes