Stereochemical Requirements for the Mineralocorticoid Receptor Antagonist Activity of Dihydropyridines

被引：37

作者：

Arhancet, Graciela B. ^{[1
]}

Woodard, Scott S. ^{[1
]}

Dietz, Jessica D. ^{[1
]}

Garland, Danny J. ^{[1
]}

Wagner, Grace M. ^{[1
]}

Iyanar, Kaliappan ^{[1
]}

Collins, Joe T. ^{[1
]}

Blinn, James R. ^{[1
]}

Numann, Randal E. ^{[1
]}

Hu, Xiao ^{[1
]}

Huang, Horng-Chih ^{[1
]}

机构：

[1] Pfizer Inc, St Louis Labs, Pfizer Global Res & Dev, St Louis, MO 63017 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 10期

关键词：

ALDOSTERONE SYNTHASE INHIBITORS; CONGESTIVE-HEART-FAILURE; SELECTIVE INHIBITORS; HYPERTENSION; PREVALENCE; MECHANISMS; CYP11B2;

D O I：

10.1021/jm1002827

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A number of known 1,4-dihydropyridine CCBs were identified as having comparable potency to the steroidal MR antagonist eplerenone. Chiral resolution of mebudipine revealed that MR and CCB activity reside in opposite enantiomers. Small molecule X-ray crystal structures showed that the C4 stereochemistry of optimized selective MR analogues, e.g. 5, is consistent with MR-active mebudipine. Molecular modeling supports a binding pose consistent with that previously proposed for DHP diesters.

引用

页码：4300 / 4304

页数：5

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