Chang Chia-En A, Ai Rizi, Gutierrez Michael, Marsella Michael J
Department of Chemistry, University of California, Riverside, CA, USA.
Methods Mol Biol. 2012;819:595-613. doi: 10.1007/978-1-61779-465-0_35.
Cannabinoids represent a promising class of compounds for developing novel therapeutic agents. Since the isolation and identification of the major psychoactive component Δ(9)-THC in Cannabis sativa in the 1960s, numerous analogues of the classical plant cannabinoids have been synthesized and tested for their biological activity. These compounds primarily target the cannabinoid receptors 1 (CB1) and Cannabinoid receptors 2 (CB2). This chapter focuses on CB1. Despite the lack of crystal structures for CB1, protein-based homology modeling approaches and molecular docking methods can be used in the design and discovery of cannabinoid analogues. Efficient synthetic approaches for therapeutically interesting cannabinoid analogues have been developed to further facilitate the drug discovery process.
大麻素是一类很有前景的化合物，可用于开发新型治疗药物。自20世纪60年代在大麻中分离并鉴定出主要的精神活性成分Δ(9)-四氢大麻酚以来，已合成了许多经典植物大麻素的类似物，并对其生物活性进行了测试。这些化合物主要作用于大麻素受体1（CB1）和大麻素受体2（CB2）。本章重点介绍CB1。尽管缺乏CB1的晶体结构，但基于蛋白质的同源建模方法和分子对接方法可用于大麻素类似物的设计和发现。已开发出针对具有治疗意义的大麻素类似物的高效合成方法，以进一步促进药物发现过程。
