Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Bioorg Med Chem. 2010 Feb;18(3):1149-62. doi: 10.1016/j.bmc.2009.12.040. Epub 2009 Dec 22.
Numerous research groups have been engaged in searching for novel CB1 receptor antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, proved to be efficacious in human for the treatment of obesity. In the present study, a series of 1,2,4-triazole-containing diarylpyrazolyl carboxamides based on the 1,5-diarylpyrazole template of rimonabant, was synthesized and tested for CB1 receptor binding affinity. The structure-activity relationship studies demonstrated that incorporation of 1,2,4-triazole ring onto the pyrazole scaffold via a methylene linker led to a significant improvement for CB1 receptor binding affinity. Importantly, these analogues also exhibited excellent selectivity for CB1 receptor over CB2 receptor.
许多研究小组一直在寻找新型 CB1 受体拮抗剂，因为 CB1 受体拮抗剂 SR141716A（利莫那班）已被证明对人类肥胖症的治疗有效。在本研究中，基于利莫那班的 1,5-二芳基吡唑模板，合成了一系列含 1,2,4-三唑的二芳基吡唑基甲酰胺，并对其 CB1 受体结合亲和力进行了测试。构效关系研究表明，通过亚甲基连接将 1,2,4-三唑环引入吡唑骨架可显著提高 CB1 受体结合亲和力。重要的是，这些类似物对 CB1 受体也表现出优异的选择性，超过 CB2 受体。
