Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone:: A potent, orally bioavailable human CB1/CB2 dual agonist with antihyperalgesic properties and restricted central nervous system penetration
Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone:: A potent, orally bioavailable human CB1/CB2 dual agonist with antihyperalgesic properties and restricted central nervous system penetration
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DOI：
10.1021/jm070317a
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发表时间：
2007-08-09
影响因子：
7.3
通讯作者：
Zadrobilek, Jiri
中科院分区：
文献类型：
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作者：
Dziadulewicz, Edward K.;Bevan, Stuart J.;Zadrobilek, Jiri
只要中枢神经系统的影响减弱，外周大麻素 CB 受体的选择性激活就有可能成为慢性疼痛的有效疗法。一类新的大麻素配体是从已知的氨烷基吲哚激动剂中合理设计出来的，并且对人类 CB1 和 CB2 受体表现出良好的结合和功能活性。这导致了一种新型 CB1/CB2 双重激动剂萘-1-基-(4-戊氧基萘-1-基)甲酮 (13) 的发现，它表现出良好的口服生物利用度、在动物模型中具有有效的抗痛觉过敏活性和有限的脑渗透性。
Selective activation of peripheral cannabinoid CB, receptors has the potential to become a valuable therapy for chronic pain conditions as long as central nervous system effects are attenuated. A new class of cannabinoid ligands was rationally designed from known aminoalkylindole agonists and showed good binding and functional activities at human CB1 and CB2 receptors. This has led to the discovery of a novel CB1/CB2 dual agonist, naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (13), which displays good oral bioavailability, potent antihyperalgesic activity in animal models, and limited brain penetration.