title: Leflunomide analogues as potential antiinflammatory agents.
abstract: 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.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Huang
authors.forename: Chiao-Li
authors.initials: CL
authors.lastname: Yang
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Lee
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Chiu
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007555:Isoxazoles; D000077339:Leflunomide