Wright W B, Brabander H J, Greenblatt E N, Day I P, Hardy R A
J Med Chem. 1978 Oct;21(10):1087-9. doi: 10.1021/jm00208a017.
A study of the pharmacological properties of pyrrolo[2,1-c][1,4]benzodiazepine derivatives led to the choice of (+)-1,2,3,11a-tetrahydro-10-methyl-5H-pyrrolol[2,1-c][1,4]benzodiazepine-5,11)10H)-dione as a candidate for anxiolytic evaluation in a limited clinical trial in man. Metabolism studies in laboratory animals have pointed to rapid hydroxylation, possibly in the 3 and 11a positions. A series of compouds containing methyl groups in one or more of these positions has been prepared in an effort to block metabolism and thereby obtain more active or longer acting compounds. All of these derivatives were less active than the parent compound.
一项关于吡咯并[2,1-c][1,4]苯二氮䓬衍生物药理特性的研究，促使人们选择(+)-1,2,3,11a-四氢-10-甲基-5H-吡咯并[2,1-c][1,4]苯二氮䓬-5,11(10H)-二酮作为在人体有限临床试验中进行抗焦虑评估的候选药物。对实验动物的代谢研究表明，可能在3位和11a位发生快速羟基化。为了阻断代谢从而获得活性更高或作用时间更长的化合物，已经制备了一系列在这些位置中的一个或多个位置含有甲基的化合物。所有这些衍生物的活性均低于母体化合物。
