大麻素受体激动剂的最新进展。
Latest advances in cannabinoid receptor agonists.
机构信息
Northeastern University, Center for Drug Discovery, 116 Mugar Hall, Boston, MA 02115, USA.
出版信息
Expert Opin Ther Pat. 2009 Dec;19(12):1647-73. doi: 10.1517/13543770903436505.
BACKGROUND
Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, Huntington's disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.
OBJECTIVE
In this review, we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists in patents that appeared during January 2008 - June 2009.
METHODS
Data presented here are obtained through the search of PubMed for research articles and reviews, and the website of European patents (http://ep.espacenet.com), SciFinder Scholar and US patents (www.uspto.gov).
CONCLUSIONS
Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.
背景
自 20 世纪 90 年代初发现大麻素受体及其内源性配体以来，内源性大麻素系统在多种病理生理过程中发挥着至关重要的作用。它已被作为治疗多种疾病的靶点，包括神经退行性疾病（帕金森病、阿尔茨海默病、亨廷顿病和多发性硬化症）、癌症、肥胖、炎症性肠病、神经性和炎性疼痛。在过去的十年中，在开发对两种大麻素受体亚型（CB1 和 CB2）具有高选择性和效力的大麻素配体方面取得了显著进展。
目的
在这篇综述中，我们强调了开发大麻素激动剂方面的最新进展，并总结了在 2008 年 1 月至 2009 年 6 月期间公布的、具有新型化学结构骨架的新型 CB 选择性激动剂的专利。
方法
此处呈现的数据是通过在 PubMed 上搜索研究文章和综述、欧洲专利网站（http://ep.espacenet.com）、SciFinder Scholar 和美国专利（www.uspto.gov）获得的。
结论
我们的分析表明，专利申请活动主要集中在 CB2 选择性激动剂领域。限制血脑屏障通透性，从而导致外周受限的 CB1/CB2 激动剂和增强 CB2 选择性，可能是避免不良的中枢 CB1 介导的副作用的必要条件。
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