Discovery Chemistry, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Bioorg Med Chem Lett. 2010 Oct 15;20(20):5984-7. doi: 10.1016/j.bmcl.2010.08.079. Epub 2010 Aug 21.
A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure-activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines. Further exploration has revealed that this class of compounds inhibits several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. Together, these properties suggest a compelling basis for their use as antitumor agents.
已鉴定出一系列新型吡唑并苯并二氮杂4（3）作为细胞周期蛋白依赖性激酶 2（CDK2）的有效抑制剂。本文描述了它们的合成和构效关系（SAR）。该类别的代表性化合物可在体外可逆地抑制 CDK2 活性，并阻断人肿瘤细胞系中的细胞周期进程。进一步的研究表明，该类化合物抑制了在癌细胞生长和分裂以及肿瘤血管生成中起关键作用的几种激酶。这些特性共同表明，它们具有作为抗肿瘤剂的应用潜力。
