title: Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2).
abstract: Recently, we proposed inhibition of aldosterone synthase (CYP11B2) as a novel strategy for the treatment of congestive heart failure and myocardial fibrosis and synthesized a large number of inhibitors. In this work, a pharmacophore model for CYP11B2 inhibitors was developed by superimposition of active and non-active compounds. This model was confirmed by the synthesis of two pyridyl substituted acenaphthene derivatives (A,B). This new class of compounds as well as the pharmacophore could be helpful for the discovery of novel inhibitors.
authors.affiliation: 8.2 Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 15 11 50, D-66041 Saarbrücken, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ulmschneider
authors.forename: Matthias
authors.initials: M
authors.lastname: Negri
authors.forename: Marieke
authors.initials: M
authors.lastname: Voets
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000073:Acenaphthenes / Q000737:chemistry; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D009281:Naphthalenes / Q000037:antagonists & inhibitors; D011485:Protein Binding; D011955:Receptors, Drug / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D000073:Acenaphthenes; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011955:Receptors, Drug; C031721:naphthalene; D019405:Cytochrome P-450 CYP11B2; C042552:acenaphthene