Studies on antiinflammatory agents. II. Synthesis and pharmacological properties of 2'-(phenylthio)methanesulfonanilides and related derivatives.
The structure of the previously reported new antiinflammatory agent (1, FK3311) was chemically modified in an attempt to find novel compounds with more potent and broader-spectrum activities. Some 2'-(phenylthio) and 2'-(phenylamino)methanesulfonanilides (2 and 3), in particular those bearing an electron-attracting substituent at the 4'-position, potently inhibited adjuvant arthritis in rats as well as collagen-induced arthritis in mice when administered orally. 4'-Carbamoyl-2'-(2,4-difluorophenylthio)methanesulfonanilide (3b), which was selected as a candidate for further development from among the compounds synthesized herein, exhibited activity in reducing arthritis in a spontaneous autoimmune disease model (MRL/lpr mice) within the dose range of 10-100 mg/kg (p.o.).
Nakamura
K
K
New Drug Research Laboratory, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Tsuji
K
K
Konishi
N
N
Okumura
H
H
Matsuo
M
M
D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013449:Sulfonamides