亲脂性血管紧张素拮抗剂辛酰基[8-亮氨酰]血管紧张素II的合成。

Synthesis of octanoyl[8-leucyl]angiotensin II, a lipophilic angiotensin antagonist.

作者信息

Paiva A C, Nouailhetas V L, Paiva T B

出版信息

J Med Chem. 1977 Jul;20(7):898-901. doi: 10.1021/jm00217a006.

Abstract

Octanoyl[8-leucyl]angiotensin II (oct-LAT) was synthesized with the aim of obtaining a longer acting angiotensin (AT) inhibitor. The new compound, with a partition coefficient K=7.00 in n-BuOH-HOAc-H2O, was compared with [Leu8]angiotensin II (LAT, K=0.18) as an AT antagonist in two isolated smooth muscle preparations and in the rat blood pressure assay. The two compounds were equally potent in the rat uterus, but LAT was more effective in the guinea pig ileum and the in vivo assay. LAT's effect was longer lasting in the smooth muscles, but the duration of in vivo inhibition was the same for the two compounds. It is concluded that partitioning between external medium and biophase is not a limiting factor for antagonistic potency and permanence of effects of 8-substituted AT derivatives.

摘要

为了获得一种作用时间更长的血管紧张素（AT）抑制剂，合成了辛酰基[8-亮氨酰]血管紧张素II（oct-LAT）。在两种离体平滑肌制剂和大鼠血压测定中，将这种在正丁醇-醋酸-水体系中分配系数K = 7.00的新化合物与[亮氨酸8]血管紧张素II（LAT，K = 0.18）作为AT拮抗剂进行了比较。这两种化合物在大鼠子宫中的效力相当，但LAT在豚鼠回肠和体内试验中更有效。LAT在平滑肌中的作用持续时间更长，但两种化合物在体内的抑制持续时间相同。结论是，外部介质和生物相之间的分配不是8-取代AT衍生物拮抗效力和作用持久性的限制因素。