Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1 H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2)

L Roumen, JW Peeters, JMA Emmen…

Index: Roumen, Luc; Peeters, Joris W.; Emmen, Judith M. A.; Beugels, Ilona P. E.; Custers, Erica M. G.; De Gooyer, Marcel; Plate, Ralf; Pieterse, Koen; Hilbers, Peter A. J.; Smits, Jos F. M.; Vekemans, Jef A. J.; Leysen, Dirk; Ottenheijm, Harry C. J.; Janssen, Henk M.; Rob Hermans Journal of Medicinal Chemistry, 2010 , vol. 53, # 4 p. 1712 - 1725

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Citation Number: 34

Abstract

Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, this is achieved with mineralocorticoid receptor antagonists, however, aldosterone synthase (CYP11B2) inhibitors may offer a promising alternative. In this study, we used three- dimensional modeling of CYP11B2 to model the binding modes of the natural substrate 18- hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a ...