Leflunomide analogues as potential antiinflammatory agents.
A series of leflunomide (1a) analogues were examined for antiinflammatory activity using the carrageenan-induced paw edema assay. Some of the compounds were significantly more potent than leflunomide, particularly those with electron-donating or negative inductive groups situated in the phenyl rings. In contrast, all the nonsubstituted compounds or with further chain-extension in the 4-position of the rings led to a decrease in activity. The LD(50) values of the most active compounds (1d, g-j) in male ICR mice were significantly greater than those of either 1a or its active metabolite 2 and therefore merit further study.
Huang
Wen-Hsin
WH
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
Yang
Chiao-Li
CL
Lee
An-Rong
AR
Chiu
Hui-Fen
HF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007555:Isoxazoles / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007555:Isoxazoles; D000077339:Leflunomide