CAJ | 학술논문

根据已知的激酶变构抑制剂与其靶点激酶的X射线共晶结构,设计了一系列以吡啶联异唑为中心结构的潜在激酶变构抑制剂。以2-甲基-5-硝基-3-吡啶甲酸甲酯为原料,通过形成酰胺、磺酰胺和连接嘧啶片段等衍生化手段合成了21个新的吡啶联异唑类化合物,其结构经1 H NMR,13 C NMR和MS确证。采用噻唑蓝( MTT)法测试了所合成化合物的体外抗肿瘤活性,初步测试结果表明该类化合物对肿瘤细胞的增长具有显著的抑制作用。
근거이지적격매변구억제제여기파점격매적X사선공정결구,설계료일계렬이필정련이서위중심결구적잠재격매변구억제제。이2-갑기-5-초기-3-필정갑산갑지위원료,통과형성선알、광선알화련접밀정편단등연생화수단합성료21개신적필정련이서류화합물,기결구경1 H NMR,13 C NMR화MS학증。채용새서람( MTT)법측시료소합성화합물적체외항종류활성,초보측시결과표명해류화합물대종류세포적증장구유현저적억제작용。
Based on the X-ray co-crystal structures of reported allosteric kinase inhibitors bound to their corresponding protein kinases, a pharmacophore model was proposed. To examine the validity of this hypothe-sis, 21 new pyridinylisoxazole derivatives were designed and synthesized. Their structures were confirmed using 1 H NMR, 13 C NMR and MS data. Their inhibitory effects against human breast cancer cell ( MCF-7 ) proliferation were evaluated. Preliminary results indicated that some of these pyridinylisoxazole derivatives possess potent anti-proliferative activities, with IC50 data in the micromolar range. The mechanism-of-action of these compounds is under investigation.