4-Anilidopiperidine analgesics. 3. 1-Substituted 4-(propananilido)perhydroazepines as ring-expanded analogues.
A study of ring-expanded analogues of the 4-(propananilido)piperidine analgesics has been undertaken in order to evaluate the influence of this structural modification on both analgesic activity and physical-dependence capacity. Thus, a series of 1-substituted 4-(propananilido)perhydroazepine derivatives was synthesized and pharmacologically evaluated in mice for analgesic activity and physical-dependence capacity. The results of this study indicate that the ring-expanded analogues of the 4-(propananilido)piperidines retain a relatively high degree of analgesic potency, except in the case of the 1-phenylethylated analogue which is approximately 150-fold less potent than the correspondingly 1-substituted piperidine analgesic. Evaluation of physical-dependence capacity of the most potent 1-substituted 4-(propananilido)perhydroazepines reveals no significant difference for these compounds as compared with morphine. The 4-(propananilido)perhydroazepines having 1-substitutents in common with known opiate antagonists failed to exhibit antagonism of morphine analgesia.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001381:Azepines / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000209:etiology
D000700:Analgesics; D001381:Azepines; D010880:Piperidines; D009270:Naloxone; D009020:Morphine