Derivatives of Apomorphine and of Other <em>N</em>-Substituted Norapomorphines

Derivatives of apomorphine and of N‐n‐propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N‐substituted derivatives and their esters was evaluated and compared to the parent compounds. The N‐n‐propyl diacetate derivative and N‐methyl and N‐n‐propyl ascorbate salts were remarkably stable to air; apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid‐catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.

制备了阿扑吗啡和N - n - 丙基去甲阿扑吗啡的衍生物，以获得改良的药理活性和增强的化学稳定性。进行了小鼠实验和犬呕吐实验，并对各种N - 取代衍生物及其酯的活性进行了评估，并与母体化合物进行了比较。N - n - 丙基二乙酸酯衍生物以及N - 甲基和N - n - 丙基抗坏血酸盐对空气具有显著的稳定性；阿扑吗啡醚化物并不比游离碱更稳定。二聚体是在吗啡酸催化重排为阿扑吗啡过程中形成的主要产物，它们都是强效的催吐剂。此外，其中两种在小鼠和犬中对吗啡表现出显著的拮抗作用。