A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.

中文翻译：

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发现新的硫代嘧啶衍生物作为有效的和口服有效的磷酸肌醇3-激酶抑制剂

已经发现了一系列新的硫代嘧啶衍生物作为有效的PI3K抑制剂。描述了这些类似物的系统SAR研究。其中，8a和9a表现出纳摩尔级的酶促活性和亚微摩尔级的细胞抗增殖活性。图8a显示了有利的药代动力学曲线，而图9a容易经历脱乙酰化以产生主要代谢物8a。此外，在NCI-H460异种移植模型中，8a和9a以剂量依赖的方式有效抑制肿瘤的生长，并具有可接受的安全性。