Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3 cells (IC₅₀ = 80 nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in vivo.

最近，磷酸肌醇3激酶（PI3K）和哺乳动物雷帕霉素靶点（mTOR）被认为是治疗癌症的有希望的靶点。在此，我们合成了一系列N- (5-(喹啉-6-基)吡啶-3-基)苯磺酰胺作为新型PI3K/mTOR双重抑制剂用于癌症治疗。在生物学评价中，化合物17e被鉴定为有效的PI3K/mTOR双重抑制剂，在低纳摩尔水平下显着抑制I类PI3K、mTOR和pAkt(Ser473)的磷酸化。此外， 17e在抗增殖测定中显示出针对 PC-3 细胞的高效力 (IC ₅₀ = 80 nM)，并显示出可接受的体内药代动力学特性。