Roark W H, Tinney F J, Cohen D, Essenburg A D, Kaplan H R
J Med Chem. 1985 Sep;28(9):1291-5. doi: 10.1021/jm00147a030.
A series of non-sulfhydryl modified dipeptides related to CI-906, CI-907, and enalapril was prepared in which various isosteric moieties (O, S, SO, SO2) have been substituted for the amino group and in which the proline residue has been replaced with various hydrophobic amino acids. The compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme and in vivo for antihypertensive activity. Compound 7c, the most potent member of this series, had an in vitro IC50 of 1.4 X 10(-8) M and showed modest oral antihypertensive activity at 30 mg/kg in conscious, two kidney, one clip Goldblatt hypertensive rats. Structure-activity relationships are discussed.
制备了一系列与CI-906、CI-907和依那普利相关的非巯基修饰二肽，其中各种等排基团（O、S、SO、SO2）取代了氨基，且脯氨酸残基被各种疏水氨基酸所取代。对这些化合物进行了体外血管紧张素转换酶抑制活性评估以及体内抗高血压活性评估。该系列中活性最强的化合物7c，其体外IC50为1.4×10(-8) M，在清醒的两肾一夹Goldblatt高血压大鼠中，30 mg/kg剂量时显示出适度的口服抗高血压活性。并讨论了构效关系。
