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

被引：62

作者：

Staples, Maree K. ^{[1
,2
]}

Grange, Rebecca L. ^{[1
,2
]}

Angus, James A. ^{[1
,3
]}

Ziogas, James ^{[1
,3
]}

Tan, Nichole P. H. ^{[1
,2
]}

Taylor, Michelle K. ^{[1
,2
]}

Schiesser, Carl H. ^{[1
,2
]}

机构：

[1] Univ Melbourne, ARC Ctr Excellence Free Rad Chem & Biotechnol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia

[2] Univ Melbourne, Sch Chem, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia

[3] Univ Melbourne, Dept Pharmacol, Melbourne, Vic 3010, Australia

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2011年 / 9卷 / 02期

关键词：

1-(CARBOXYBENZYL)IMIDAZOLE-5-ACRYLIC ACIDS; BENZO(B)SELENOPHENE DERIVATIVES; ANGIOTENSIN; POTENT; THERAPY; ANALOGS;

D O I：

10.1039/c0ob00573h

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：473 / 479

页数：7

共 31 条

[21] Eprosartan - A review of its use in the management of hypertension [J].