新型5-氨基-2-(苄基硫代)噻唑-4-甲酰胺类化合物的设计、合成及抗肿瘤活性  

Design,synthesis and anti-tumor activity of novel 5-amino-2-(benzylthio)thiazole-4-carboxamide derivatives

作　　者：王璐[1,2] 尤启冬[1,2] 姜正羽 

机构地区：[1]中国药科大学江苏省药物分子设计与成药性优化重点实验室,南京21009 [2]中国药科大学药物化学教研室,南京21009

出　　处：《中国药科大学学报》2017年第1期16-22,共7页Journal of China Pharmaceutical University

基　　金：高等学校博士学科点专项科研基金资助项目(No.2013009611002);国家"重大新药创制"科技重大专项资助项目(No.2013ZX09402102)~~

摘　　要：为了寻找具有更好抗肿瘤活性的化合物,设计合成了一系列5-氨基-2-(苄基硫代)噻唑-4-甲酰胺衍生物。以2-氨基-2-氰基-乙酰胺为起始原料,合成了16个化合物DDO-5401~DDO-5416;目标化合物结构经IR、1H NMR和ESI-MS确证;采用MTT法对目标化合物进行5株肿瘤细胞(HCT116、Hep G2、A549、MDA-MB-231、MCF-7)体外抗肿瘤活性测定。合成的化合物对肿瘤细胞尤其是A549细胞表现出了良好的抑制活性;构效关系研究表明,苯环上连有给电子基团的化合物抑制活性要好于连有吸电子基团的化合物。化合物DDO-5413的抑制活性最强,对乳腺癌细胞MDA-MB-231和MCF-7抑制活性好于阳性对照药达沙替尼,值得进一步研究。A series of 5-amino-2-（ benzylthio） thiazole-4-carboxamide derivatives were designed and synthesized to discover novel compounds with anti-tumor activity.Compounds DDO-5401-DDO-5416 were synthesized using2-amino-2-cyanoacetamide as the start material.The structures of the synthesized compounds were confirmed by IR,~1H NMR and ESI-MS.The in vitro anti-tumor activities of the synthesized compounds were determined by MTT assay in HCT116,Hep G2,A549,MDA-MB-231 and MCF-7 cell lines.Target compounds showed good antitumor activity especially in A549 cell line.SAR study showed that electron donating groups were more favorable than electron absorption ones.Compound DDO-5413 exhibited noteworthy activity in MDA-MB-231 and MCF-7cell lines with IC_（50） value lower than the positive reference dasatinib.It suggested that DDO-5413 might be the candidate for further investigation.

关 键 词：5-氨基-2-(苄基硫代)噻唑-4-甲酰胺类衍生物 合成 抗肿瘤活性 

分 类 号：R91[医药卫生—药学] R914.5R96