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HERO ID
2708522
Reference Type
Journal Article
Title
1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: A new class of potent and selective aldosterone synthase inhibitors
Author(s)
Grombein, CM; Hu, Q; Heim, R; Rau, S; Zimmer, C; Hartmann, RW
Year
2015
Is Peer Reviewed?
Yes
Journal
European Journal of Medicinal Chemistry
ISSN:
0223-5234
EISSN:
1768-3254
Volume
89
Page Numbers
597-605
Language
English
PMID
25462268
DOI
10.1016/j.ejmech.2014.10.027
Web of Science Id
WOS:000348003500049
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940472958&doi=10.1016%2fj.ejmech.2014.10.027&partnerID=40&md5=ae0219d1f7dbdd609cbcf261cf7c89c4
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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.
Keywords
Aldosterone; Aldosterone synthase; 1-Phenylsulfinyl-3-(pyridin-3-yl); naphthalen-2-ols; 11 beta-hydroxylase; Selectivity
Tags
IRIS
•
Naphthalene
Database Searches - Nov 2015 (private)
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PubMed
WOS
Combined data set
Data set for title/abstract screening
Excluded - PECO criteria not met (TIAB)
Other
•
Naphthalene (2021 Evidence mapping publication)
Database Searches - Nov 2015 (private)
Previous HERO references
Database Searches
PubMed
WOS
Combined data set
Data set for title/abstract screening
Excluded – PECO criteria not met
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