We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC₅₀ of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies.

我们确定了一系列新的喹喔啉-2-羧酸衍生物，针对莫洛尼鼠白血病病毒1（Hs Pim-1）激酶的人类前病毒整合位点。合成了十七个类似物，为研究结构-活性关系提供了有用的见识。在Hs Pim-1的ATP口袋中实现的对接研究与这些抑制剂的非经典结合模式一致。铅化合物1能够在纳摩尔浓度（IC ₅₀为74 nM）下阻断Hs Pim-1的酶促活性，对一组哺乳动物蛋白激酶具有良好的选择性。体外对人类慢性髓样白血病细胞株KU812的研究显示，在微摩尔浓度下具有抗肿瘤活性。结果，化合物1代表了设计新型抗癌靶向疗法的有希望的先导。