102676-29-9Relevant academic research and scientific papers
Synthesis, Biological Evaluation, and Molecular Modeling of 1 -Benzyl-1H-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)
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
experimental part, p. 1712 - 1725 (2010/07/17)
Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, this is achieved, with mineralocorticoid, receptor antagonists, however, aldosterone synthase (CYP 11B2) 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 rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead, MOERAS 115 (4-((5-phenyl-1H-imidazol-1-yl)methyl) benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC 50 for CYP11B26.0 nM, selectivity 19.8). Molecular docking of the inhibitors in the models enabled us to generate posthoc hypotheses on their binding modes, providing a valuable basis for future studies and further design of CYP11B2 inhibitors.
N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors
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Page/Page column 7-8, (2009/09/26)
The invention relates to the use of a N-benzyl 5-substituted imidazole derivative having the general formula I wherein R is (C1-3)alkyl, (C1-3)alkyloxy, halogen, nitro or cyano; R1 is (C1-6)alkyl, optionally substituted with OH, (C1-3)alkyloxy, (C1-3)alkylcarbonyloxy, (C1-3)alkyloxycarbonyl or halogen, or (C1-3)alkyloxycarbonyl; or R1 is phenyl, optionally substituted with 1-3 substituents independently selected from (C1-3)alkyl, (C1-3)alkyloxy, hydroxylmethyl and halogen; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a disorder or disease in a subject mediated by aldosterone synthase or responsive to inhibition of aldosterone synthase.
Fedrazole Hydrochloride: A Potent, Selective, Nonsteroidal Inhibitor ofAromatase for the Treatment of Estrogen-Dependent Disease
Browne, L. J.,Gude, C.,Rodriguez, H.,Steele, R. E.
, p. 725 - 736 (2007/10/02)
A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered.The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazopyridin-5-yl)benzonitrile monohydrochloride, 26a.
