苯酰胺类c-Met激酶抑制剂的合成及其体外抗肿瘤活性研究  

Synthesis of benzamide compounds c-Met inhibitors and its anti-tumor activities in vitro

作　　者：张晶[1] 程璐[1] 梁泰刚[1] 班树荣[1] 李青山[1] 胡龙勤 

机构地区：[1]山西医科大学药学院,山西太原030001 [2]Ernest Mario School of Pharmacy,Rutgers The State University of New Jersey

出　　处：《现代药物与临床》2016年第9期1313-1318,共6页Drugs & Clinic

摘　　要：目的设计和合成苯酰胺类c-Met激酶抑制剂,并测定其体外抗肿瘤活性。方法以4-氯-6,7二甲氧基喹啉、6-氯-7-氮杂嘌呤和4-氯-7-氮杂吲哚为起始物,经取代、还原和缩合反应制备目标化合物3a^5c,并采用噻唑蓝法(MTT)测定目标化合物对GTL-16细胞的抑制作用。结果合成了9个化合物,其结构经MS、1H-NMR和13C-NMR确证。化合物3a^5c对GTL-16细胞均呈现不同程度的抑制作用,其中化合物3c对GTL-16细胞的IC50达到411 nmol/L。结论苯酰胺类化合物具有抑制GTL-16细胞活性的作用,值得进一步深入研究。Objective To design and synthesize benzamide compounds c-Met inhibitors, and study their anti-tumor activities in vitro. Methods 6,7-Dimethoxy-4-chloroquinoline, 6-chloro-7-deazapurinepurine, and 4-chloro-7-azaindole were used as starting material to synthesize the target compounds 3a-5c by substitution, reduction and condensation reactions. The antitumor activities of the compounds against GTL-16 cells were investigated by methyl thiazolyl tetrazoliym （MTT） assay. Results Nine novel benzamide compounds were synthesized. The structures were characterized by MS, 1H-NMR, and 13C-NMR techniques. All of the compounds had different extents potency of antitumor activities against GTL-16 cells. Especially the IC50 value of the compound 3c was 411 nmol/L. Conclusion Benzamide compounds have good antitumor activities against GTL-16 cells, which could be a valuable candidate for further development.

关 键 词：苯酰胺类 c-Met激酶抑制剂 合成 GTL-16细胞 抑制 

分 类 号：R979.1[医药卫生—药品]