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J Med Chem. 2014 Jun 26;57(12):5011-22. doi: 10.1021/jm401430e. Epub 2014 Jan 24.

Aldosterone synthase inhibitors as promising treatments for mineralocorticoid dependent cardiovascular and renal diseases.

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1
Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) , Campus C2.3, D-66123 Saarbr├╝cken, Germany.

Abstract

Besides the well-known roles of aldosterone as a mineralocorticoid in regulating homeostasis of electrolytes and volume, recent studies revealed that it is also a potent proinflammation factor inducing reactive oxygen species and up-regulating a panel of fibrosis related genes. Under pathological circumstances, excessive aldosterone is involved in a lot of chronic diseases, including hypertension, cardiac fibrosis, congestive heart failure, ventricular remodeling, and diabetic nephropathy. Therefore, the inhibition of aldosterone synthase (CYP11B2), which is the pivotal enzyme in aldosterone biosynthesis, was proposed as a superior approach. Expected pharmacodynamic effects have been demonstrated in both animal models and clinical trials after the application of CYP11B2 inhibitors. The importance of selectivity over other steroidogenic CYP enzymes, in particular 11╬▓-hydroxylase (CYP11B1), was also revealed. Recently, much more selective CYP11B2 inhibitors have been reported, which could be promising drug candidates for the treatment of aldosterone related diseases.

PMID:
24422519
DOI:
10.1021/jm401430e
[Indexed for MEDLINE]

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