2-Substituted 1-azabicycloalkanes, a new class of non-opiate antinociceptive agents.
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.
Carson
J R
JR
Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477-0776.
Carmosin
R J
RJ
Vaught
J L
JL
Gardocki
J F
JF
Costanzo
M J
MJ
Raffa
R B
RB
Almond
H R
HR
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
D000700:Analgesics; D007212:Indolizines; D011763:Pyrrolizidine Alkaloids; D011807:Quinolizines