Tully W R, Gardner C R, Gillespie R J, Westwood R
Roussel Laboratories Ltd., Wiltshire, U.K.
J Med Chem. 1991 Jul;34(7):2060-7. doi: 10.1021/jm00111a021.
Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivated conflict test thought to predict anxiolytic properties. Compounds 4, 5, and 13 were equipotent with chlordiazepoxide but showed little or no myorelaxant effects. Replacing the oxadiazole group by thiazole gave compounds such as 23 which binds to the benzodiazepine receptor but exhibits the intrinsic activity of a partial inverse agonist in vivo.
已发现，在一系列咪唑并[1,2-a]嘧啶中，恶二唑如同苯甲酰基一样，是苯二氮䓬受体配体中酯基在代谢方面的稳定替代基团。这一变化已产生了许多与受体结合的化合物，并且这些化合物在被认为可预测抗焦虑特性的食物激发冲突试验中表现出强效激动剂活性。化合物4、5和13与氯氮䓬等效，但几乎没有或没有肌松作用。用噻唑取代恶二唑基团得到了如化合物23这样的化合物，它能与苯二氮䓬受体结合，但在体内表现出部分反向激动剂的内在活性。
