Liu, Zhiqing; Chen, Haiying; Wang, Pingyuan; Li, Yi; Wold, Eric A.; Leonard, Paul G.; Joseph, Sarah; Brasier, Allan R.; Tian, Bing; Zhou, Jia published the artcile< Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation>, SDS of cas: 112253-70-0, the main research area is arylquinazolinone arylchromone preparation inhibitor BRD4 antiinflammatory agent; structure arylquinazolinone arylchromone antiinflammatory activity inhibition BRD4; selectivity arylchromone inhibition BRD4 pharmacokinetics metabolism hERG CYP.
Arylquinazolinones and arylchromenones such as I (X = CH2, MeN) were prepared as selective inhibitors of bromodomain-containing protein 4 (BRD4) for potential use as orally bioavailable antiinflammatory agents. I inhibited BRD4 with IC50 values of 67-84 nM and were selective for BRD1 over binding domains of BRD2, BRD3, and BRDT and over CBP; I inhibited the expression of Toll-like receptor (TLR3)-induced inflammatory genes in vitro and inhibited airway inflammation in mice. The pharmacokinetics (t1/2, AUC, Cmax, and clearance), metabolic stability of I (X = NMe) in murine and human cells, and inhibition of cytochrome P450 enzymes and hERG by I (X = MeN) were determined The structure of I (X = NMe) bound to human BRD4 binding domain 1 was determined by X-ray crystallog.
Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 112253-70-0 belongs to class amides-buliding-blocks, and the molecular formula is C7H7BrN2O, SDS of cas: 112253-70-0.
Referemce:
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