854583-85-0Relevant articles and documents
Heteroatom insertion into 3,4-dihydro-1 H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase
Grombein, Cornelia M.,Hu, Qingzhong,Rau, Sabrina,Zimmer, Christina,Hartmann, Rolf W.
supporting information, p. 788 - 796 (2015/02/19)
Aldosterone synthase (CYP11B2) catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. CYP11B2 is regarded as a new target for several cardiovascular diseases which are associated with chronically elevated aldosterone levels such as hypertension, congestive heart failure and myocardial fibrosis. In this paper, we optimized heterocycle substituted 3,4-dihydropyridin-2(1H)-ones as CYP11B inhibitors by systematic introduction of heteroatoms and by bioisosteric exchange of the lactame moiety by a sultame moiety. The most promising compounds regarding inhibition of human CYP11B2 and selectivity versus human enzymes CYP11B1, CYP17, and CYP19 were tested for inhibition of rat CYP11B2. Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2. 2 μM).
Inhibitors of the Human Aldosterone Sythase CYP11B2
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Page/Page column 33, (2011/05/16)
The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and a method of treating of hyperaldosteronism and/or disorders or diseases that are mediated by 11β-hydroxylase (CYP11B1) with these compounds.
6-PYRIDIN-3-YL-3,4-DIHYDRO-1H-QUINOLIN-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN ALDOSTERONE SYNTHASE CYP11B2
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Page/Page column 50, (2010/01/29)
The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and the use of these compounds and other heteroaryl substituted quinolinone derivatives for the treatment of hyperaldosteronism and/or disorders or diseases that are mediated by 11 β-hydroxylase (CYP11 B1 ).