综述ccr2拮抗剂研究进展.pdfVIP

现代药物与临床 Drugs Clinic 第 26 卷 第 3 期 2011 年 5 月 • 161 • • 综 述 • CCR2 拮抗剂研究进展 蔡志强，袁 静，黄长江，李祎亮，徐为人，汤立达 天津药物研究院 天津市新药设计与发现重点实验室，天津 300193 摘 要：细胞表面趋化因子受体 2 （CCR2 ）属于 G 蛋白偶联受体 （GPCR ）超家族成员，并且是单核细胞趋化蛋白 1～4 （MCP 1～4 ）的受体。MCP 1～4 是促炎症反应的化学诱导物，CCR2 和 MCP-1 在人类侵蚀性疾病模型如动脉粥状硬化、多发性硬 化症中均起显著作用。大量研究证明 CCR2 和 MCP-1 拮抗剂可以减少临床炎症模型的发病率，这些化学拮抗剂的结构多样， 主要包括 γ-氨基丁酰胺类、甘胺酰胺类、噻唑类、吲哚类、二取代双哌啶醇类、季铵盐类和不饱和杂环类等，它们表现出不 同的药理活性。CCR2 拮抗剂对各种与趋化因子相关的疾病具有较好的疗效，部分药物已经进入临床试验阶段，综述 CCR2 及其受体拮抗剂的研究进展。 关键词：CCR2 ；CCR2 拮抗剂；药理作用；构效关系；作用机制 中图分类号：R979.9 文献标识码：A 文章编号：1674-5515(2011)03 - 0161 - 07 Advances in study on chemokine receptor 2 antagonists CAI Zhi-qiang, YUAN Jing, HUANG Chang-jiang, LI Yi-liang, XU Wei-ren, TANG Li-da Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: CC Chemokine Receptor 2 (CCR2) is a member of the G protein-coupled receptor (GPCR) superfamily that serves as the receptor for monocyte chemoattractant proteins 1—4 (MCP-1 to -4), a group of pro-inflammatory chemotactic cytokines (chemokines). Many researches proved that CCR2 and the MCP-1 antagonist compound reduced the clinical inflammation model disease incidence rate, MCP-1 and CCR2 play the remarkable role in the human corrosive disease model like artery gruel shape hardening and the multiple scierosis. Its chemistry antagonist compound with the structural diversity, including 4-aminobutanamide antagonists, glycinamide antagonists, thiazole antagonists, indole antagonists, disubstituted piperidine alcohols antagonists, quaternary ammonium salts antagonists, and unsaturated heterocyclic antagonists, has displayed the different medicine activeness. CCR2 antagonists have good effect on various chemokine-related diseases, and some d