Synthesis of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine and related compounds as potential analgesics.
Several analogues (21 and 29-50) of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine (1) were prepared, a compound that had been found to have marked antinociceptive activity in the inflamed-paw pressure test in rats. Two synthetically versatile methods leading to these compounds are described. In this series, antinociceptive activity increases with increasing size of the amine substituent, reaching an optimum with N(Me)Et (32), but this is always associated with central nervous system (CNS) stimulant activity. The antinociceptive activity of these compounds is most likely due to an action that is similar to that of amphetamine rather than to an interaction with an opiate receptor. The endo diastereoisomer 22 and the benzo analogue 11 were both devoid of antinociceptive and CNS stimulant activity.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects
D000700:Analgesics; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; C036953:3-phenylbicyclo(3.2.1)oct-3-en-2-amine; D000109:Acetylcholine