The discovery of 1-(5-chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as a new class of potent (IC(50) values of 3-10 nM) and selective inhibitors of Chk1 kinase was described. One of these compounds (2e) potentiates HeLa cells by over 22-fold against doxorubicin in an antiproliferation assay, and SW620 cells against camptothecin by 20-fold in an antiproliferation assay and 14-fold in a soft agar assay. Flow cytometry (FACS) analysis confirmed that 2e abrogated G2 checkpoint arrest of H1299 cells caused by doxorubicin and S checkpoint arrest caused by camptothecin.

中文翻译：

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1-（5-氯-2-烷氧基苯基）-3-（5-氰基吡嗪-2-基）脲[氰基吡嗪的校正]作为Chk1激酶的有效和选择性抑制剂：合成，初步SAR和生物活性。

1-（5-氯-2-烷氧基苯基）-3-（5-氰基吡嗪-2-基）脲类化合物作为新型有效化合物（IC（50）值为3-10 nM）和Chk1选择性抑制剂的发现描述了激酶。这些化合物之一（2e）在抗增殖试验中对阿霉素的HeLa细胞增效超过22倍，在抗增殖试验中对喜树碱的SW620细胞增效20倍，在软琼脂试验中对喜树碱的增效能力为14倍。流式细胞仪（FACS）分析证实2e消除了由阿霉素引起的H1299细胞的G2检查点停滞和由喜树碱引起的S检查点停滞。