Université Bordeaux Segalen, Pharmacochimie, FRE 3396, F-33000 Bordeaux, France.
Eur J Med Chem. 2013 Jul;65:205-22. doi: 10.1016/j.ejmech.2013.04.051. Epub 2013 May 3.
Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors.
在此，我们描述了取代的苯基氨基吡咯并[1,2-a]喹喔啉-羧酸衍生物的合成和性质，这些衍生物是一类新型的强效人蛋白激酶 CK2 抑制剂。使用方便、直接的合成方案设计并合成了一组 15 种化合物。对这些化合物抑制人蛋白激酶 CK2 的活性进行了测试，CK2 是人蛋白激酶家族的一种酶，是许多疾病（包括炎症性疾病和癌症）的潜在药物靶点。确定了具有微摩尔和亚微摩尔范围内的 IC50 的新型抑制剂。最有前途的化合物是 4-[(3-氯苯基)氨基]吡咯并[1,2-a]喹喔啉-3-羧酸 1c，其对人 CK2 的抑制作用的 IC50 为 49 nM。我们的研究结果表明，吡咯并[1,2-a]喹喔啉是进一步开发和优化人蛋白激酶 CK2 抑制剂的有前途的起始支架。
