Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):471-4. doi: 10.1016/j.bmcl.2010.10.114. Epub 2010 Oct 28.
Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.
我们小组之前的研究成果表明，吡唑并[1,5-a]嘧啶是开发强效和选择性细胞周期蛋白依赖性激酶（CDK）抑制剂的可行核心。作为利用吡唑并[1,5-a]嘧啶核心作为设计和合成强效和选择性激酶抑制剂模板的一部分，我们专注于细胞周期进程中的关键调节剂 CHK1。对吡唑并[1,5-a]嘧啶核心的 C5 和 C6 位置的进一步 SAR 研究，结合之前在 C3 和 C7 位置披露的 SAR，发现了强效和选择性的 CHK1 抑制剂。
