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