Novartis Institutes for Biomedical Research, Emeryville, CA, USA.
Bioorg Med Chem Lett. 2010 Dec 1;20(23):6895-8. doi: 10.1016/j.bmcl.2010.10.021. Epub 2010 Oct 13.
PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described.
PI3 激酶是一类脂质激酶，介导多种细胞过程，如增殖、迁移和分化。PI3 激酶途径在癌症中经常通过 PI3Kα 过表达、基因扩增、突变和 PTEN 磷酸酶缺失而失调。因此，PI3K 抑制剂是癌症治疗的一种有吸引力的治疗方式。本文描述了一系列新型 PI3K 抑制剂，它们具有嘧啶核心结构，在生化测定和细胞中对 I 类 PI3 激酶具有显著的活性。描述了该化学型的发现、合成和 SAR。
