Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1.
The preparation and analgesic activities of a series of the entitled compounds (5-22) and the optical isomers of the 1-cyclohexyl derivative 5 are described. Reactions of N,N-bis(2-chloroethyl)-1,2-diphenylethylamine (3) with ammonia and primary amines gave N-(1,2-diphenylethyl)piperazine (4) and N1-substituted derivatives (5-20, 22), respectively. The alkylation of 4 afforded 12-21. Compounds 5-18 and 22 were also obtained by the reactions of 1,2-diphenylethylamine (23) and N-substituted 2,2'-dichlorodiethylamine. Racemate 5 was resolved with (+)- or (-)-2'-nitrotartranilic acid into its optical isomers [(+)-5 and (-)-5], and the absolute configuration of (+)-5 was determined to be S configuration by the synthesis and optical rotatory dispersion measurements. The most active members in this series of compounds were 5-7, which were approximately as potent as (-)-morphine. In the case of 5, the more potent enantiomer (S)-(+)-5 has the opposite configuration to that of (-)-N,N-dimethyl-1,2-diphenylethylamine (Spa) or (-)-morphine with respect to the (C-9) asymmetric center and belongs to a new series of compounds having potent analgesic activity.
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D009904:Optical Rotation; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011809:Quinones; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D010879:Piperazines; D011809:Quinones