蛋白酶激活受体-4拮抗剂的研究进展.pdfVIP

现代药物与临床 Drugs Clinic 第 32 卷 第 12 期 2017 年 12 月 ·2529 · • 综 述 • 蛋白酶激活受体-4 拮抗剂的研究进展 1 2* 3 2 3 解晓帅 ，路 楠 ，黄长江 ，许佑君 ，刘登科 1. 天津市第一中心医院 药学部，天津 300192 2. 沈阳药科大学 制药工程学院，辽宁 沈阳 110016 3. 天津药物研究院，天津 300193 摘 要：蛋白酶激活受体-4 （PAR-4 ）是一个由300 个氨基酸经过 7 次跨膜形成的 G 蛋白偶联受体，它可通过与凝血酶的结 合诱导血小板聚集，参与凝血过程。因此，PAR-4 受体可以作为抗血小板药物的新靶点。近年来研究者发现了 3 种不同结构 类型的小分子 PAR-4 受体拮抗剂，分别含有吲唑、吲哚和咪唑并噻二唑结构。对这几种拮抗剂的结构、药理活性等方面的 研究进展进行综述。 关键词：蛋白酶激活受体-4 ；抗血小板药物；PAR-4 受体拮抗剂；吲唑；吲哚；咪唑并噻二唑 中图分类号：R973 文献标志码：A 文章编号：1674 - 5515(2017)12 - 2529 - 05 DOI: 10.7501/j.issn.1674-5515.2017.12.052 Research progress on PAR-4 inhibitors 1 2 3 2 3 XIE Xiao-shuai , LU Nan , HUANG Chang-jiang , XU You-jun , LIU Deng-ke 1. Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China 2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China 3. Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: Protease-activated receptor-4 (PAR-4) is a G protein-coupled receptor formed by 300 amino acids through 7 transmembrane. It can induce platelet aggregation by binding to the thrombin, and participate in the process of blood coagulation. As a result, PAR-4 can be considered as a very valuable potential treatment of antiplatelet target. In recent years, three type of small molecules PAR-4 inhibitors, including indazoles, indoles, and imidazothiadiazoles have been developed. Research progress on the structure and pharmacological activities of PAR-4 inhibitors are reviewed in this paper. Key words: protease-activated receptor-4 (PAR-4); antiplatelet drugs; PAR-4 inhibitors; indazoles; indoles; imidazothiadiazoles