title: Computer-assisted rational design, synthesis, and bioassay of non-steroidal anti-inflammatory agents.
abstract: A focused dataset of previously synthesized and tested [1,2,4]-triazolo[1,5-a]pyridines and pyridine-3-carboxylates was studied by Molecular Field Topology Analysis (MFTA) to identify steric and electronic determinants of anti-inflammatory activity useful for the design and synthesis of new anti-inflammatory agents. Rational design based on the MFTA model identified eleven novel pyridine-3-carboxylates (2a-e and 3a-f) as promising. After synthesis and screening, three of (2a, 2c, 3a) revealed potent anti-inflammatory activity exceeding that of indomethacin, the reference inhibitor for artificially induced edema in rats.
authors.affiliation: Pesticide Chemistry Department, National Research Centre, Dokki, 12622 Cairo, Egypt.
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Tala
authors.forename: Polina V
authors.initials: PV
authors.lastname: Oliferenko
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Oliferenko
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D017076:Computer-Aided Design; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D007213:Indomethacin