Borgman R J, Baldessarini R J, Walton K G
J Med Chem. 1976 May;19(5):717-9. doi: 10.1021/jm00227a026.
A series of diesters of apomorphine was synthesized to serve as prodrugs. They were converted in vivo to free apomorphine, which could be detected in the brain. Stereotyped gnawing behavior and unilateral rotation similar to that produced by apomorphine were induced by all of the diesters but the time course of action of the latter was prolonged. The duration of action generally increased with the size of the ester substituent and appeared to correlate inversely with the rate of hydrolysis of the esters by liver extracts. It is concluded that the diesters serve as prodrugs of apomorphine and their prolonged duration is partly explained by a decreasing rate of hydrolysis attributable to increased steric hindrance at the acyl carbon atoms.
合成了一系列阿扑吗啡二酯作为前药。它们在体内转化为游离阿扑吗啡，可在脑中检测到。所有二酯均诱导出与阿扑吗啡产生的类似的刻板啃咬行为和单侧旋转，但后者的作用时间进程延长。作用持续时间一般随酯取代基大小增加，且似乎与肝提取物对酯的水解速率呈负相关。结论是二酯作为阿扑吗啡的前药，其作用时间延长部分是由于酰基碳原子处空间位阻增加导致水解速率降低所致。
