Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor was written by Zhao, Yujun;Zhou, Bing;Bai, Longchuan;Liu, Liu;Yang, Chao-Yie;Meagher, Jennifer L.;Stuckey, Jeanne A.;McEachern, Donna;Przybranowski, Sally;Wang, Mi;Ran, Xu;Aguilar, Angelo;Hu, Yang;Kampf, Jeff W.;Li, Xiaoqin;Zhao, Ting;Li, Siwei;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2018.COA of Formula: C20H16ClN3O2 This article mentions the following:
We report the structure-based discovery of CF53 (28) as a highly potent and orally active inhibitor of bromodomain and extra-terminal (BET) proteins. By the incorporation of a NH-pyrazole group into the 9H-pyrimido[4,5-b]indole core, we identified a series of compounds that bind to BRD4 BD1 protein with Ki values of <1 nM and achieve low nanomolar potencies in the cell growth inhibition of leukemia and breast cancer cells. The most-promising compound, CF53, possesses excellent oral pharmacokinetic properties and achieves significant antitumor activity in both triple-neg. breast cancer and acute leukemia xenograft models in mice. Determination of the co-crystal structure of CF53 with the BRD4 BD1 protein provides a structural basis for its high binding affinity to BET proteins. CF53 is very selective over non-BET bromodomain-containing proteins. These data establish CF53 as a potent, selective, and orally active BET inhibitor, which warrants further evaluation for advanced preclin. development. In the experiment, the researchers used many compounds, for example, (S)-2-(6-(4-Chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamide (cas: 1380087-89-7COA of Formula: C20H16ClN3O2).
(S)-2-(6-(4-Chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamide (cas: 1380087-89-7) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. The weakness of this bond allows the ring opening of these heterocycles under reductive conditions. As with isoxazolines, isoxazoles may be cleaved using low-valent titanium obtained from the Kulinkovich reaction.This procedure affords enaminoketones from 2,4-substituted isoxazoles.COA of Formula: C20H16ClN3O2
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem