1. Beijing Inst Pharmacol & Toxicol, Lab Comp Aided Drug Design & Discovery, Beijing 100850, Peoples R China
2. Wuhan Inst Technol, Hubei Key Lab Novel Chem Reactor & Green Chem Tec, Wuhan 430073, Hubei, Peoples R China
折叠
Abstract
A novel series of PI3K (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3K, , , and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.
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