108748-26-1Relevant 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.
, p. 788 - 796 (2015)
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).
N-{[2-(PIPERIDIN-1-YL)PHENYL](PHENYL)METHYL}-2-(3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXA ZIN-7-YL)ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ROR-GAMMA MODULATORS FOR TREATING AUTOIMMUNE DISEASES
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Page/Page column 68; 109, (2018/08/20)
The present invention provides e.g. N-{[2-(piperidin-1-yl)phenyl] (phenyl)methyl}-2-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)acetamide derivatives and related compounds as ROR-gamma modulators for treating e.g. autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases or cholestatic diseases, such as e.g. arthitis and asthma.
