1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors.

Grombein, Cornelia M; Hu, Qingzhong; Heim, Ralf; Rau, Sabrina; Zimmer, Christina; Hartmann, Rolf W

dc.contributor.author	Grombein, Cornelia M
dc.contributor.author	Hu, Qingzhong
dc.contributor.author	Heim, Ralf
dc.contributor.author	Rau, Sabrina
dc.contributor.author	Zimmer, Christina
dc.contributor.author	Hartmann, Rolf W
dc.date.accessioned	2015-02-25T10:38:26Z	en
dc.date.available	2015-02-25T10:38:26Z	en
dc.date.issued	2015-01-07	en
dc.identifier.citation	1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors. 2015, 89:597-605 Eur J Med Chem	en
dc.identifier.issn	1768-3254	en
dc.identifier.pmid	25462268	en
dc.identifier.doi	10.1016/j.ejmech.2014.10.027	en
dc.identifier.uri	http://hdl.handle.net/10033/345291	en
dc.description.abstract	1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols and related compounds were synthesized and evaluated for inhibition of aldosterone synthase (CYP11B2), a potential target for cardiovascular diseases associated with elevated plasma aldosterone levels like congestive heart failure and myocardial fibrosis. Introduction of substituents at the phenylsulfinyl moiety and changes of the substitution pattern at the naphthalene core were examined. Potent compounds were further examined for selectivity versus other important steroidogenic CYP enzymes, i.e. the highly homologous 11β-hydroxylase (CYP11B1), CYP17 and CYP19. The most potent compound (IC50 = 14 nM) discovered was the meta-trifluoromethoxy derivative 11, which also exhibited excellent selectivity toward CYP11B1 (SF = 415), and showed no inhibition of CYP17 and CYP19.
dc.language.iso	en	en
dc.title	1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus C23, D-66123 Saarbrücken, Germany.	en
dc.identifier.journal	European journal of medicinal chemistry	en
refterms.dateFOA	2018-06-13T09:14:54Z
html.description.abstract	1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols and related compounds were synthesized and evaluated for inhibition of aldosterone synthase (CYP11B2), a potential target for cardiovascular diseases associated with elevated plasma aldosterone levels like congestive heart failure and myocardial fibrosis. Introduction of substituents at the phenylsulfinyl moiety and changes of the substitution pattern at the naphthalene core were examined. Potent compounds were further examined for selectivity versus other important steroidogenic CYP enzymes, i.e. the highly homologous 11β-hydroxylase (CYP11B1), CYP17 and CYP19. The most potent compound (IC50 = 14 nM) discovered was the meta-trifluoromethoxy derivative 11, which also exhibited excellent selectivity toward CYP11B1 (SF = 415), and showed no inhibition of CYP17 and CYP19.