The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation.
The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation.
复制标题
DOI：
10.4137/pmc.s32171
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Rimoldi JM
中科院分区：
文献类型：
--
作者：
Bow EW;Rimoldi JM
大麻素是从大麻中分离出来的一类看似简单的萜酚次生代谢物，以(−)-Δ9-tetrahydrocannabinol （THC）突出显示，引起主要由大麻素受体（CB1或CB2）信号传导介导的独特药理作用。自从四氢大麻酚和相关大麻素被发现以来，人们对合成和半合成的经典大麻素类似物进行了评估，以帮助确定受体结合模式和结构- cb1 /CB2功能活性关系。这一观点将研究经典大麻素，特别强调五个区域的构效关系：C3侧链，酚羟基，芳香a环，吡喃b环和环己烯基c环。迄今为止，累积的结构-活性关系研究已经帮助确定了CB1和CB2的效力和选择性所需的关键结构元件，更重要的是，引领了具有增强的物理化学和药理特征的当代非经典大麻素调节剂的发现和发展。
The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles.