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有机化学
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有机化学 ›› 2013, Vol. 33 ›› Issue (03): 590-595.DOI: 10.6023/cjoc201211019 上一篇    下一篇

研究论文

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

金秋a,b, 辛敏行b, 丛欣b, 尤启冬a   

  1. a 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;
    b 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
  • 收稿日期:2012-11-09 修回日期:2012-12-03 发布日期:2012-12-06
  • 通讯作者: 尤启冬 E-mail:youqidong@gmail.com
  • 基金资助:

    江苏省自然科学基金(No. BK2011086)资助项目.

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

Jin Qiua,b, Xin Minhangb, Cong Xinb, You Qidonga   

  1. a Jiangsu Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing 210009;
    b Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing 210042
  • Received:2012-11-09 Revised:2012-12-03 Published:2012-12-06
  • Supported by:

    Project supported by the National Science Foundation of Jiangsu Province (No. BK2011086).

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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 pharmacophore conformation through an intramolecular hydrogen bond. Twelve compounds were synthesized and the inhibitory effect on PARP activity of these compounds were tested and evaluated. The results showed that all the target compounds displayed potency against the PARP enzyme, and compound 7c was the most potent one with an IC50 value of 20.5 nmol稬-1.

Key words: PARP inhibitor, Benzofuran-7-carboxamide, anti-tumor , synthesis