Tandem free-radical addition/substitution chemistry and its application to the preparation of novel AT1 receptor antagonists??

Organic & Biomolecular Chemistry Pub Date: 2010-11-03 DOI: 10.1039/C0OB00573H

Abstract

Benzothiophene and benzoselenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT1 receptor antagonist properties. While the sulfur-containing systems were prepared following existing methodology, the selenium-containing analogues required the development of novel, tandem free-radical chemistry involving addition of aryl radicals to alkynes, followed by intramolecular homolytic substitution at the higher heteroatom. All four compounds prepared proved to be excellent AT1 receptor antagonists, with pKB estimates of 7.2–9.5.

Graphical abstract: Tandem free-radical addition/substitution chemistry and its application to the preparation of novel AT1 receptor antagonists
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