title: 2-Substituted 1-azabicycloalkanes, a new class of non-opiate antinociceptive agents.
abstract: 2-Substituted 1-azabicycloalkanes (3- and 5-aryloctahydroindolizines 2 and 11, 3-cyclohexyloctahydroindolizine 12, 4-aryloctahydroquinolizines 13, and 3-arylhexahydropyrrolizines 14) constitute a new class of non-opiate antinociceptive agents. These compounds demonstrated activity in the mouse abdominal constriction test and many were active in the mouse tail-flick test. trans-3-(2-Bromophenyl)octahydroindolizine (2a) did not bind to the opiate receptor nor did it affect arachidonate metabolism. 3-Aryloctahydroindolizines were prepared by catalytic hydrogenation of 1-aryl-3-(2-pyridinyl)-2-propen-1-ones. The X-ray crystal structure of (-)-2a was determined and absolute stereochemistry assigned as 3-R,8a-R.
authors.affiliation: Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477-0776.
authors.forename: J R
authors.initials: JR
authors.lastname: Carson
authors.forename: R J
authors.initials: RJ
authors.lastname: Carmosin
authors.forename: J L
authors.initials: JL
authors.lastname: Vaught
authors.forename: J F
authors.initials: JF
authors.lastname: Gardocki
authors.forename: M J
authors.initials: MJ
authors.lastname: Costanzo
authors.forename: R B
authors.initials: RB
authors.lastname: Raffa
authors.forename: H R
authors.initials: HR
authors.lastname: Almond
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D007212:Indolizines / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis / Q000494:pharmacology*; D011807:Quinolizines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D000700:Analgesics; D007212:Indolizines; D011763:Pyrrolizidine Alkaloids; D011807:Quinolizines