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Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update.大麻素受体2（CB2）激动剂和拮抗剂：专利综述
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Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists.发现1a,2,5,5a-四氢-1H-2,3-二氮杂环丙[a]戊搭烯-4-甲酰胺作为强效和选择性CB2受体激动剂。
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Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a).烟碱酸受体（GPR109a）的强效三环吡唑四唑激动剂。
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Characterizing cannabinoid CB2 receptor ligands using DiscoveRx PathHunter beta-arrestin assay.使用DiscoveRx PathHunter β-抑制蛋白检测法对大麻素CB2受体配体进行表征。
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Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons.大麻素受体CB2在人类感觉神经元中的定位以及激动剂介导的辣椒素反应抑制作用。
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APD371的发现：一种用于治疗慢性疼痛的高效且选择性的CB激动剂的鉴定。

Discovery of APD371: Identification of a Highly Potent and Selective CB Agonist for the Treatment of Chronic Pain.

作者信息

Han Sangdon, Thoresen Lars, Jung Jae-Kyu, Zhu Xiuwen, Thatte Jayant, Solomon Michelle, Gaidarov Ibragim, Unett David J, Yoon Woo Hyun, Barden Jeremy, Sadeque Abu, Usmani Amin, Chen Chuan, Semple Graeme, Grottick Andrew J, Al-Shamma Hussein, Christopher Ronald, Jones Robert M

机构信息

Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, California 92121, United States.

出版信息

ACS Med Chem Lett. 2017 Nov 30;8(12):1309-1313. doi: 10.1021/acsmedchemlett.7b00396. eCollection 2017 Dec 14.

DOI:10.1021/acsmedchemlett.7b00396
PMID:29259753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5733264/
Abstract

The discovery of a novel, selective and fully efficacious CB agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB receptor to avoid tachyphylaxis. Based on its overall favorable preclinical profile, (APD371) was selected for further development for the treatment of pain.

摘要

本文描述了一种新型、选择性且完全有效的CB激动剂的发现，其具有令人满意的药代动力学和药物性质。化合物在口服给药后对骨关节炎疼痛的大鼠模型有效，并且与吗啡不同，在为期5天的亚慢性治疗模式中维持其镇痛效果。这些数据与我们的假设一致，即CB受体的有效内化和再循环需要完全激动剂效力以避免快速耐受性。基于其总体良好的临床前特征，选择（APD371）进行疼痛治疗的进一步开发。