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dc.contributor.authorGrombein, Cornelia M
dc.contributor.authorHu, Qingzhong
dc.contributor.authorHeim, Ralf
dc.contributor.authorRau, Sabrina
dc.contributor.authorZimmer, Christina
dc.contributor.authorHartmann, Rolf W
dc.date.accessioned2015-02-25T10:38:26Zen
dc.date.available2015-02-25T10:38:26Zen
dc.date.issued2015-01-07en
dc.identifier.citation1-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 Chemen
dc.identifier.issn1768-3254en
dc.identifier.pmid25462268en
dc.identifier.doi10.1016/j.ejmech.2014.10.027en
dc.identifier.urihttp://hdl.handle.net/10033/345291en
dc.description.abstract1-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.isoenen
dc.title1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus C23, D-66123 Saarbrücken, Germany.en
dc.identifier.journalEuropean journal of medicinal chemistryen
refterms.dateFOA2018-06-13T09:14:54Z
html.description.abstract1-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.


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