Synthetic analgesics: N-(1-[2-arylethyl]-4-substituted 4-piperidinyl) N-arylalkanamides.
The synthesis of several 4-arylamino-4-piperdinecarboxylic acids is reported. These acids were starting materials for the preparation of alpha-amino esthers, ethers and ketones. Different synthetic approaches are described. Suitable substitution on both nitrogen atoms afforded extremely potent analgesics. Thus, methyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate (22),N-(4-(methoxymethyl)-2-[2-(2-thienyl)ethyl]-4-piperidinyl)-N-phenylpropranamide (67) and N-[4-acetyl-1-(2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide (82) were found to be respectively 7682, 3987 and 4921 times as potent as morfine. Both cis- and trans-3-methyl homologs of 22 have been prepared. As expected, analgesic activity resides mainly in the cis-isomer.
D000698:Analgesia; D000701:Analgesics, Opioid / Q000138:chemical synthesis*; D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D005283:Fentanyl / Q000031:analogs & derivatives; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D000813:Anilides; D010880:Piperidines; D005283:Fentanyl