183322-18-1Relevant articles and documents
Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors
Chen, Zhe-Sheng,Dai, Qing-Qing,Li, Guo-Bo,Liu, Hong-Min,Liu, Hui,Wang, Bo,Wang, Shaomeng,Yu, Bin,Yuan, Shuo,Zhang, Jing-Ya,Zhang, Xiao-Nan,Zuo, Jia-Hui
, p. 14895 - 14911 (2021/10/12)
The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.
4-arylmercaptoquinazoline compound as well as preparation method and medical application thereof
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Paragraph 0024; 0026, (2021/01/24)
The invention discloses a 4-arylmercaptoquinazoline compound as well as a preparation method and medical application thereof. The 4-arylmercaptoquinazoline compound is reported for the first time. Research finds that the 4-arylmercaptoquinazoline compound has LSD1 inhibitory activity and has a prospect of being developed into antitumor drugs. Taking the compound 1 as an example, the IC50 value ofthe compound for inhibiting the LSD1 protein is 0.69 [mu]M and is remarkably superior to that of positive control; and in an anti-tumor test, the compound has relatively strong inhibitory activity ongastric cancer MGC-803, gastric cancer BGC-823, gastric cancer SGC-7901, breast cancer MCF-7, lung cancer H1650, lung cancer A549, lung cancer H1975, lung cancer H460, esophageal cancer EC-109, livercancer HepG2 and leukemia THP1 cells, and has a prospect of being developed into medicines for resisting gastric cancer, breast cancer, lung cancer, cancer of the esophagus, liver cancer and leukemia.
Transition-metal and oxidant-free approach for the synthesis of diverse N-heterocycles by TMSCl activation of isocyanides
Chen, Fen-Er,Dong, Lin,Li, Hongyan,Liu, Jinxin,Luo, Liangliang,Xiao, You-Cai,Zhou, Yuan
, p. 29257 - 29262 (2020/10/02)
A highly efficient TMSCl-mediated addition of N-nucleophiles to isocyanides has been achieved. This transition-metal and oxidant-free strategy has been applied to the construction of various N-heterocyles such as quinazolinone, benzimidazole and benzothiazole derivatives by the use of distinct amino-based binucleophiles. The notable feature of this protocol includes its mild reaction condition, broad functional group tolerance and excellent yield. This journal is