title: Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines and related compounds.
abstract: Modification of some 8-benzylidene-5,6,7,8-tetrahydroquinolines, which have good antiulcer activity, led to three distinct classes of compounds with good in vivo antiinflammatory activity. Initial efforts led to a series of alkenes derived from 5,6,7,8-tetrahydroquinolines substituted at the 8-position. A second approach concentrated on replacing the CH linkage of these 8-benzylidene-substituted compounds with other spacer groups and increasing the size of the cycloalkyl ring from a six- to seven-membered ring, which provided 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine analogues. Finally, the substituent was switched from the cycloalkyl ring to the 2-position of the pyridine ring. Variation of the 2-substituent was also examined. Optimal antiinflammatory activity after oral administration was found in both the rat carrageenan paw edema and rat developing adjuvant arthritis models with 2-substituted 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridines, and of particular interest was 27 (WY-28342).
authors.affiliation: Department of Medicinal Chemistry, Wyeth Research (U.K.) Ltd., Taplow, Maidenhead, Berkshire, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Calhoun
authors.forename: R P
authors.initials: RP
authors.lastname: Carlson
authors.forename: R
authors.initials: R
authors.lastname: Crossley
authors.forename: L J
authors.initials: LJ
authors.lastname: Datko
authors.forename: S
authors.initials: S
authors.lastname: Dietrich
authors.forename: K
authors.initials: K
authors.lastname: Heatherington
authors.forename: L A
authors.initials: LA
authors.lastname: Marshall
authors.forename: P J
authors.initials: PJ
authors.lastname: Meade
authors.forename: A
authors.initials: A
authors.lastname: Opalko
authors.forename: R G
authors.initials: RG
authors.lastname: Shepherd
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D005260:Female; D008297:Male; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011804:Quinolines