苯并呋喃类聚腺苷二磷酸核糖聚合酶(PARP)抑制剂的设计、合成及活性研究  

Design, Synthesis and Activity of Benzofuran-7-carboxamide Poly(ADP-ribose)-polymerase Inhibitors

作　　者：金秋[1,2] 辛敏行[2] 丛欣[2] 尤启冬[1] 

机构地区：[1]江苏省药物分子设计与成药性优化重点实验室中国药科大学,南京210009 [2]江苏省抗肿瘤分子靶向药物重点实验室江苏先声药业有限公司,南京210042

出　　处：《有机化学》2013年第3期590-595,共6页Chinese Journal of Organic Chemistry

基　　金：江苏省自然科学基金(No.BK2011086)资助项目~~

摘　　要：苯并呋喃类聚腺苷二磷酸核糖聚合酶(PARP)是抗肿瘤治疗的一个有效靶点.本研究根据现有PARP抑制剂的结构特征,设计并合成了未见文献报道的12个苯并呋喃类化合物,并进行了初步体外活性筛选.实验结果表明所合成的化合物均显示出一定的PARP抑制活性,其中化合物7c的活性与阳性对照药Veliparib活性相当,IC50为20.5 nmol·L-1。Poly-（ADP-ribose）-polymerase （PARP） is a promising anti-cancer target as it plays a crucial role in the cellular reparation and survival mechanisms. A series of benzofuran-7-carboxamides was designed to maintain the required pharma- cophore conformation through an intramolecular hydrogen bond. Twelve compounds were synthesized and the inhibitory ef- fect on PARP activity of these compounds were tested and evaluated. The results showed that all the target compounds dis- played potency against the PARP enzyme, and compound 7c was the most potent one with an IC50 value of 20.5 nmol·L-1.

关 键 词：抗肿瘤 PARP 苯并呋喃 合成 

分 类 号：TQ460.1[化学工程—制药化工]