SYNTHESIS OF NEW POTENTIAL ANALGESIC COMPOUNDS

A series of 6-phenyl-, 6-(3-methoxyphenyl)-, and 6-(3-hydroxyphenyl)-2-azabicyclo{4.2.1}nonanes was synthesized by a sequence involving alkylation of an appropriate 2-arylcyclopentanone with N,N-dimethylaminopropyl chloride. Bromination at the other alpha position on the cyclopentanone ring followed by ring closure afforded a methobromide. Demethylation of the methobromide followed by Wolff-Kishner reduction afforded 6-aryl-2-methyl-2-azabicyclo{4.2.1}nonanes.;Analogs of 6-phenyl-3-azabicyclo{4.2.1}nonanes were synthesized by a sequence of alkylation on the 2-phenylcyclopentanone with N,N-dimethylaminoethyl chloride, monodemethylation, Mannich reaction and Wolff-Kishner reduction. Demethylation and alkylation on the resulting free amine afforded analogs of 6-phenyl-3-azabicyclo{4.2.1}nonanes.;Among the analogs tested, 6-(3-methoxyphenyl)-, 6-(3-methoxyphenyl)-2-methyl-, and 6-(3-hydroxyphenyl)-2-phenethyl-2-azabicyclo{4.2.1}nonanes showed antinociceptive activity comparable to codeine in mouse hot-plate assay. Some analogs showed only mild antinociceptive activity but most analogs were either inactive or toxic.;Analogs of 5-phenyl-3-azabicyclo{3.2.1}octanes were synthesized by a sequence of Mannich reactions on the the 2-phenylcyclopentanone followed by Wolff-Kishner reduction, demethylation and alkylation.