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

2.50
Hdl Handle:
http://hdl.handle.net/10033/345291
Title:
1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors.
Authors:
Grombein, Cornelia M; Hu, Qingzhong; Heim, Ralf; Rau, Sabrina; Zimmer, Christina; Hartmann, Rolf W
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.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus C23, D-66123 Saarbrücken, Germany.
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
Journal:
European journal of medicinal chemistry
Issue Date:
7-Jan-2015
URI:
http://hdl.handle.net/10033/345291
DOI:
10.1016/j.ejmech.2014.10.027
PubMed ID:
25462268
Type:
Article
Language:
en
ISSN:
1768-3254
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorGrombein, Cornelia Men
dc.contributor.authorHu, Qingzhongen
dc.contributor.authorHeim, Ralfen
dc.contributor.authorRau, Sabrinaen
dc.contributor.authorZimmer, Christinaen
dc.contributor.authorHartmann, Rolf Wen
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.en
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

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