Synthesis of angiotensin II antagonists containing sarcosine in position 7

Analogues of the type [1-sarcosine,7-sarcosine, 8-X]angiotensin II, where X = isoleucine, leucine, alanine, methionine, O-methylthreonine, or DL-alloisoleucine, were synthesized by the solid-phase method and purified by partition chromatography, cation-exchange chromatography, and high-pressure liquid chromatography. In the isolated rat uterus, these analogues had activities of less than 0.1, less than 0.1, less than 0.1, less than 0.1, less than 0.1, and 0.7%, respectively, of the hyotropic activity of angiotensin II and inhibited the contractile response to angiotensin II with pA2 values of 8.1, 7.2, 6.7, 7.7, 7.4, and 8.4, respectively. In the vagotomized ganglion blocked rat, the analogues had 0.7, 0.21, 0.06, 0.72, 0.13, and 12.5%, respectively, of the pressor activity of angiotensin II.