120078-30-0Relevant articles and documents
Synthesis, radio-synthesis and in vitro evaluation of terminally fluorinated derivatives of HU-210 and HU-211 as novel candidate PET tracers
Zanato, Chiara,Pelagalli, Alessia,Marwick, Katie F. M.,Piras, Monica,Dall'Angelo, Sergio,Spinaci, Andrea,Pertwee, Roger G.,Wyllie, David J. A.,Hardingham, Giles E.,Zanda, Matteo
, p. 2086 - 2096 (2017)
We report the synthesis of terminally fluorinated HU-210 and HU-211 analogues (HU-210F and HU-211F, respectively) and their biological evaluation as ligands of cannabinoid receptors (CB1 and CB2) and N-methyl d-aspartate receptor (NMDAR). [18F]-labelled HU-210F was radiosynthesised from the bromo-substituted precursor. In vitro assays showed that both HU-210F and HU-211F retain the potent pharmacological profile of HU-210 and HU-211, suggesting that [18F]-radiolabelled HU-210F and HU-211F could have potential as PET tracers for in vivo imaging.
Novel Labelled Cannabinergic Ligands and Related Analogs
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Paragraph 0152; 0156, (2021/10/02)
Novel cannabinoid ligands represented by the general formulas I, II, and III and methods for preparation and use within which one or more of a fluorescent ligand, nitroxide spin label, metal chelate, biotin moiety, or group with enhanced polarity may be incorporated. The compounds can bind to and modulate the cannabinoid CB1 and CB2 receptors and thereby considered specific ligands for these receptors. Some of the disclosed compounds that bind to cannabinoid CB1 and CB2 receptors can exhibit tight or irreversible binding characteristics for these receptors. Due to the presence of the imaging/diagnostic and/or therapeutic functional groups including fluorescent groups, nitroxide spin labels, metal chelates, biotin moieties, and groups with enhanced polarity, the disclosed compounds may be useful as imaging/diagnostic tools and/or therapeutic agents.
Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures
Hua, Tian,Li, Xiaoting,Wu, Lijie,Iliopoulos-Tsoutsouvas, Christos,Wang, Yuxia,Wu, Meng,Shen, Ling,Brust, Christina A.,Nikas, Spyros P.,Song, Feng,Song, Xiyong,Yuan, Shuguang,Sun, Qianqian,Wu, Yiran,Jiang, Shan,Grim, Travis W.,Benchama, Othman,Stahl, Edward L.,Zvonok, Nikolai,Zhao, Suwen,Bohn, Laura M.,Makriyannis, Alexandros,Liu, Zhi-Jie
, p. 655 - 18,665 (2020/02/18)
Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1. Here, we report the cryoelectron microscopy structures of synthetic cannabinoid-bound CB2 and CB1 in complex with Gi, as well as agonist-bound CB2 crystal structure. Of important scientific and therapeutic benefit, our results reveal a diverse activation and signaling mechanism, the structural basis of CB2-selective agonists design, and the unexpected interaction of cholesterol with CB1, suggestive of its endogenous allosteric modulating role. Structure and simulations of cannabinoid receptors CB2 and CB1 in their inactive, active-like, and activated signaling states reveal residue differences that may provide G protein selectivity, the distinct binding behavior of CB2 agonists in CB2 and CB1, as well as evidence for modulation of CB1 by cholesterol binding.
PROCESS FOR THE PREPARATION OF HU-910 AND CRYSTALLINE STRUCTURE THEREOF
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Page/Page column 31, (2018/05/27)
The invention provides processes for the preparation of HU-910, which are scalable to industrial purposes, using safer reagents and having high yield and pure product and a crystalline structure of HU-910, which is a unique product thereof.
