Issue 2, 2011

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

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

Supplementary files

Article information

Article type
Paper
Submitted
13 Aug 2010
Accepted
21 Sep 2010
First published
03 Nov 2010

Org. Biomol. Chem., 2011,9, 473-479

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

M. K. Staples, R. L. Grange, J. A. Angus, J. Ziogas, N. P. H. Tan, M. K. Taylor and C. H. Schiesser, Org. Biomol. Chem., 2011, 9, 473 DOI: 10.1039/C0OB00573H

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