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Author, Editor(s)
Author(s):
Voets, Marieke
Antes, Iris
Scherer, Christiane
Müller-Vieira, Ursula
Biemel, Klaus
Marchais-Oberwinkler, Sandrine
Hartmann, Rolf W.		dblp
dblp
dblp
dblp
dblp
dblp
dblp
Not MPG Author(s):
Voets, Marieke
Scherer, Christiane
Müller-Vieira, Ursula
Biemel, Klaus
Marchais-Oberwinkler, Sandrine
Hartmann, Rolf W.

BibTeX cite key*:

Antes2006a

Title

Title*:

Synthesis and evaluation of heteroaryl substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis

Journal

Journal Title*:

Journal of Medicinal Chemistry
Journal's URL:


Download URL
for the article:

http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/jm060055x
Language:

English

Publisher

Publisher's
Name:


Publisher's URL:


Publisher's
Address:


ISSN:


Vol, No, pp, Date

Volume*:

49
Number:

7

Publishing Date:

2006

Pages*:

2222-2231
Number of
VG Pages:

9

Page Start:

2222
Page End:

2231

Sequence Number:


DOI:


Note, Abstract, ©

Note:


(LaTeX) Abstract:

In this study, the synthesis and biological evaluation of heteroaryl-substituted dihydronaphthalenes and indenes
(1-16) is described. The compounds were tested for activity by use of human CYP11B2 expressed in
fission yeast and V79 MZh cells and for selectivity by use of human CYP11B1, CYP17, and CYP19. The
most active inhibitor was the 6-methoxydihydronaphthalene 4 (IC50 ) 2 nM), showing a Ki value of 1.3 nM
and a competitive type of inhibition. The 5-methoxyindene 3 was found to be the most selective CYP11B2
inhibitor (IC50 ) 4 nM; CYP11B1 IC50 ) 5684 nM), which also showed only marginal inhibition of human
CYP3A4 and CYP2D6. Docking and molecular dynamics studies using our homology-modeled CYP11B2
structure were performed to understand some structure-activity relationships. Caco-2 cell experiments
revealed highly cell-permeable compounds, and metabolic studies with 4 using rat liver microsomes showed
sufficient stability.

URL for the Abstract:


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Keywords:


HyperLinks / References / URLs:

http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/jm060055x

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Access Level:

Intranet

Correlation
MPG Unit:
Max-Planck-Institut für Informatik
MPG Subunit:
Computational Biology and Applied Algorithmics
Appearance:
MPII WWW Server, MPII FTP Server, MPG publications list, university publications list, working group publication list, Fachbeirat, VG Wort


BibTeX Entry:

@ARTICLE{Antes2006a,
AUTHOR = {Voets, Marieke and Antes, Iris and Scherer, Christiane and M{\"u}ller-Vieira, Ursula and Biemel, Klaus and Marchais-Oberwinkler, Sandrine and Hartmann, Rolf W.},
 TITLE = {Synthesis and evaluation of heteroaryl substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase {(CYP11B2)} for the treatment of congestive heart failure and myocardial fibrosis},
 JOURNAL = {Journal of Medicinal Chemistry},
 YEAR = {2006},
 NUMBER = {7},
 VOLUME = {49},
 PAGES = {2222--2231},
}

Entry last modified by Christine Kiesel, 05/08/2007
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Editor(s)
Iris Antes		Created
12/22/2005 13:55:31
Revisions
9.
8.
7.
6.
5.		Editor(s)
Christine Kiesel
Iris Antes
Iris Antes
Iris Antes
Iris Antes		Edit Dates
08.05.2007 21:21:56
03/26/2007 03:10:31 PM
03/13/2007 04:55:01 PM
03/13/2007 04:48:58 PM
03/13/2007 04:47:05 PM