Turner S, Myers M, Gadie B, Hale S A, Horsley A, Nelson A J, Pape R, Saville J F, Doxey J C, Berridge T L
Department of Medicinal Chemistry, Reckitt and Colman plc, Kingston-upon-Hull, United Kingdom.
J Med Chem. 1988 May;31(5):906-13. doi: 10.1021/jm00400a004.
Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11. The iminoimidazolidine 93 showed a somewhat longer duration of action than the guanidine derivatives. Preliminary studies in a pithed rat preparation indicated that these thiadiazole derivatives (11, 63, and 93) lowered blood pressure by a direct relaxant effect on vascular smooth muscle.
一些2-芳基-5-胍基-（或N-取代胍基）-1,3,4-噻二唑及其密切相关的类似物被发现可降低皮质激素（DOCA）高血压大鼠的血压。在毒性较低的未取代胍中，当芳基为2-甲基苯基环时，活性最佳（11）。对胍基的修饰并未增加抗高血压活性，但在2-甲基苯基系列中，N-正丁基-和N-（2-甲氧基乙基）胍（63和78）以及相关的亚氨基咪唑烷93与未取代胍11的活性相当。亚氨基咪唑烷93的作用持续时间比胍衍生物略长。在去大脑大鼠制备中的初步研究表明，这些噻二唑衍生物（11、63和93）通过对血管平滑肌的直接舒张作用来降低血压。
