3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2.

Yin, Lina; Hu, Qingzhong; Hartmann, Rolf W

dc.contributor.author	Yin, Lina
dc.contributor.author	Hu, Qingzhong
dc.contributor.author	Hartmann, Rolf W
dc.date.accessioned	2013-02-21T08:04:32Z
dc.date.available	2013-02-21T08:04:32Z
dc.date.issued	2012
dc.identifier.citation	3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2. 2012, 7 (11):e48048 PLoS ONE	en_GB
dc.identifier.issn	1932-6203
dc.identifier.pmid	23133610
dc.identifier.doi	10.1371/journal.pone.0048048
dc.identifier.uri	http://hdl.handle.net/10033/269912
dc.description.abstract	Aldosterone synthase (CYP11B2) is a promising therapeutic target for the treatment of cardiovascular diseases related to abnormally high aldosterone levels. On the basis of our previously identified lead compounds I-III, a series of 3-pyridinyl substituted aliphatic cycles were designed, synthesized and tested as CYP11B2 inhibitors. Aromaticity abolishment of the core was successfully applied to overcome the undesired CYP1A2 inhibition. This study resulted in a series of potent and selective CYP11B2 inhibitors, with compound 12 (IC(50) = 21 nM, SF = 50) as the most promising one, which shows no inhibition toward CYP1A2 at 2 µM. The design conception demonstrated in this study can be helpful in the optimization of CYP inhibitor drugs regarding CYP1A2 selectivity.
dc.language.iso	en	en
dc.rights	Archived with thanks to PloS one	en_GB
dc.title	3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2.	en
dc.type	Article	en
dc.contributor.department	Pharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.	en_GB
dc.identifier.journal	PloS one	en_GB
refterms.dateFOA	2018-06-12T17:49:31Z
html.description.abstract	Aldosterone synthase (CYP11B2) is a promising therapeutic target for the treatment of cardiovascular diseases related to abnormally high aldosterone levels. On the basis of our previously identified lead compounds I-III, a series of 3-pyridinyl substituted aliphatic cycles were designed, synthesized and tested as CYP11B2 inhibitors. Aromaticity abolishment of the core was successfully applied to overcome the undesired CYP1A2 inhibition. This study resulted in a series of potent and selective CYP11B2 inhibitors, with compound 12 (IC(50) = 21 nM, SF = 50) as the most promising one, which shows no inhibition toward CYP1A2 at 2 µM. The design conception demonstrated in this study can be helpful in the optimization of CYP inhibitor drugs regarding CYP1A2 selectivity.