82594-80-7Relevant articles and documents
1,(3,)5-substituted imidazoles, useful in the treatment of hypertension and methods for their preparation
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Paragraph 0171; 0172; 0173, (2016/03/04)
The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds in hydrophilic or lipophilic form, which are useful as angiotensin II ATI receptor antagonists suitable for transdermal delivery. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases.
LRRK2 INHIBITORS
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Page/Page column 111, (2013/02/28)
Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.
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.