Kang Suk Youn, Lee Sung-Han, Seo Hee Jeong, Jung Myung Eun, Ahn Kwangwoo, Kim Jeongmin, Lee Jinhwa
Small Molecule Group, Central Research Institute, Green Cross Corporation, 341 Bojeong-Dong, Giheung-Gu, Yongin, Gyunggi-Do 446-799, Republic of Korea.
Bioorg Med Chem Lett. 2008 Apr 1;18(7):2385-9. doi: 10.1016/j.bmcl.2008.02.061. Epub 2008 Feb 29.
Cannabinoid CB1 receptors have been the focus of extensive studies since the first clinical results of rimonabant (SR141716) for the treatment of obesity and related metabolic disorders were reported in 2001. To further evaluate the properties of CB receptors, we have designed a new series of tetrazole-biarylpyrazoles. The various analogues were efficiently prepared and bio-assayed for binding to cannabinoid CB1 receptor. Six of the new compounds which displayed high in vitro CB1 binding affinities were assayed for binding to CB2 receptor. Noticeably, cyclopentyl-tetrazole (9a) demonstrated good binding affinity and selectivity for CB1 receptor (IC(50)=11.6nM and CB2/CB1=366).
自2001年报道了利莫那班（SR141716）治疗肥胖及相关代谢紊乱的首批临床结果以来，大麻素CB1受体一直是广泛研究的焦点。为了进一步评估CB受体的特性，我们设计了一系列新的四唑-联芳基吡唑。高效制备了各种类似物，并对其与大麻素CB1受体结合进行了生物测定。对六种在体外显示出高CB1结合亲和力的新化合物进行了与CB2受体结合的测定。值得注意的是，环戊基-四唑（9a）对CB1受体表现出良好的结合亲和力和选择性（IC(50)=11.6nM，CB2/CB1=366）。
