title: Benzofuro[2,3-c]pyridin-6-ols: synthesis, affinity for opioid-receptor subtypes, and antinociceptive activity.
abstract: A general synthetic approach to a novel series of cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols is described together with their receptor-binding profile on opioid-receptor subtypes (mu, kappa, delta). In addition, their in vivo antinociceptive activity was assessed. A number of the analogues synthesized showed potent affinity for opioid receptors and have potent antinociceptive activity in a mouse phenylquinone abdominal stretching model. In addition, the SAR for nitrogen substitution in the above series is explored with respect to the overall opioid receptor subtype binding profile. In general it was found that substituents which enhanced mu and kappa binding affinity in the benzomorphan series had a similar effect in the benzofuropyridine series described in this manuscript. An overlap hypothesis topologically connecting the benzomorphan nucleus to the cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridine nucleus is also presented.
authors.affiliation: Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hutchison
authors.forename: R
authors.initials: R
authors.lastname: de Jesus
authors.forename: M
authors.initials: M
authors.lastname: Williams
authors.forename: J P
authors.initials: JP
authors.lastname: Simke
authors.forename: R F
authors.initials: RF
authors.lastname: Neale
authors.forename: R H
authors.initials: RH
authors.lastname: Jackson
authors.forename: F
authors.initials: F
authors.lastname: Ambrose
authors.forename: B J
authors.initials: BJ
authors.lastname: Barbaz
authors.forename: M A
authors.initials: MA
authors.lastname: Sills
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D012026:Reflex, Stretch / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D011725:Pyridines; D011957:Receptors, Opioid