[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 2. Modifications of the oxyacetic side chain.

doi:10.1021/JM00378A011

Paper

[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 2. Modifications of the oxyacetic side chain.

Published Dec 1, 1984 · J. Plattner, A. Fung, J. R. Smital

Journal of medicinal chemistry

Q1 SJR score

3

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0

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Abstract

The discovery of high-ceiling natriuretic activity from a series of aminomethyl derivatives of ethyl [2,3-dichloro-4-(4-hydroxybenzoyl)phenoxy]acetate prompted our continued investigation of this new class of (aryloxy)acetic acid diuretics. Systematic alteration of the oxyacetic side chain has shown that the carboxylic acid function is the active species in vivo and that the ethyl ester group serves as a prodrug to enhance oral absorption. Side-chain functional groups that are incapable of generating the carboxylic acid in vivo failed to impart diuretic activity to the target compounds. Additional side-chain modifications including homologation, methyl substitution, and heteroatom replacement are also described. Ring annelation of the oxyacetic side chain to a dihydrobenzofuran-2-carboxylic acid produced compound 32, which displayed the highest level of saluretic activity for this series.

Study Snapshot

This study demonstrates that carboxylic acid function is the active species in vivo, and that side-chain modifications can enhance oral absorption and diuretic activity in this new class of diuretics.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 2. Modifications of the oxyacetic side chain.

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