کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372308 | 981868 | 2013 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K](/preview/png/1372308.png)
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 how the potency of a benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping. This effort led to the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 16, 15 August 2013, Pages 4652–4656