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

Maree K. Staples; Rebecca L. Grange; James A. Angus; James Ziogas; Nichole P. H. Tan; Michelle K. Taylor; Carl H. Schiesser

doi:10.1039/C0OB00573H

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

Maree K. Staples,^a^b Rebecca L. Grange,^a^b James A. Angus,^a^c James Ziogas,^a^c Nichole P. H. Tan,^a^b Michelle K. Taylor^a^b^d and Carl H. Schiesser*^a^b

Author affiliations

* Corresponding authors

^a ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, The University of Melbourne, Victoria, Australia

^b School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia
E-mail: carlhs@unimelb.edu.au
Fax: +61 3 9347 8189
Tel: +61 3 8344 2432

^c Department of Pharmacology, The University of Melbourne, Victoria, Australia

^d Current address: Division of Chemistry, School of Science and Technology, The University of New England, Armidale, Australia

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 pK_B estimates of 7.2–9.5.

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Publication details

The article was received on 13 Aug 2010, accepted on 21 Sep 2010 and first published on 03 Nov 2010

Article type: Paper

DOI: 10.1039/C0OB00573H

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

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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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Organic & Biomolecular Chemistry

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

Abstract

Supplementary files

Publication details

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

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