Studies on angiotensin converting enzyme inhibitors. III. 2-Carboxyethylcarbamoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.
- 1 January 1985
- journal article
- research article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 33 (5) , 2011-2022
- https://doi.org/10.1248/cpb.33.2011
Abstract
(3S)-2-[N-Substituted N-(2-carboxyethyl)carbamoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives and their monoester compounds were synthesized by condensation of (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylates, 3-aminopropionates and phosgene, followed by deprotection of ester groups. Their in vitro angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationship is discussed. Some of the N-ethylcarbamoyl analogs which had hydrophobic substituents (C8H17-C12H25, CH2CH2Ph) at the .alpha.-position to the carboxyl group in the side chain, showed potent in vitro ACE inhibitory activities with IC50 [median inhibitory concentration] values of 4.0-8.8 .times. 10-9 M. The monoesters reduced the systolic blood pressure by more than 30 mmHg in spontaneously hypertensive rats (SHR) at an oral dose of 50 mg/kg.This publication has 14 references indexed in Scilit:
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