Tandem free-radical addition/substitution chemistry and its application to the preparation of novel AT1 receptor antagonists.
Benzothiophene and benzoselenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT(1) 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 AT(1) receptor antagonists, with pK(B) estimates of 7.2-9.5.
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, 3010, Australia.
Maree K
MK
Staples
Rebecca L
RL
Grange
James A
JA
Angus
James
J
Ziogas
Nichole P H
NP
Tan
Michelle K
MK
Taylor
Carl H
CH
Schiesser
D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D015394:Molecular Structure
D047228:Angiotensin II Type 1 Receptor Blockers; D005609:Free Radicals