Identification of Cannabigerol-Derived Dual CB2 Receptor Agonists and TRPM8 Antagonists with Anti-Inflammatory and Analgesic Activities
文献类型：期刊论文
| 作者 | Yang, Wenjiao6,7; Sun, Haiguo7; Ji, Jing4,5; Chen, Hai3; Cheng, Jiaxin4,7; Hu, Zhengtao3; Gong, Xudong6; Liu, Qi6; Peng, Su2; Suo, Jin7
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2025-06-20 |
| 卷号 | 68期号:13页码:13335-13357 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.4c03220 |
| 英文摘要 | Emerging evidence suggests that compounds possessing both CB2 receptor (CB2R) agonist and TRPM8 antagonist activities may offer effective pain relief while minimizing the severe side effects commonly associated with current analgesics. In this study, we designed and synthesized a series of novel cannabigerol (CBG) derivatives with the goal of identifying potent dual ligands that act as both CB2R agonists and TRPM8 antagonists. Structure-activity relationship studies revealed that the introduction of an amide group at the C-2 position or alkylation at the C-3 position of CBG is essential for enhancing CB2R agonistic and TRPM8 antagonistic activities. CBG amides 2a and 6b exhibited dual activity as CB2R agonists and TRPM8 antagonists, displaying notable anti-inflammatory and analgesic efficacy alongside a favorable safety profile. Notably, compound 8b, a prodrug of 6b, demonstrated improved oral plasma exposure and enhanced analgesic effects in mice. |
| WOS关键词 | POTENTIAL CHANNELS ; IN-VITRO ; PAIN ; CANNABINOIDS ; OPTIMIZATION ; ADMETLAB ; MODULATE ; PLATFORM ; TARGETS ; SYSTEM |
| 资助项目 | Ministry of Science and Technology of the People's Republic of China[2021ZD0200900] ; STI2030-Major Projects[SIMM0420245006-1] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[24ZR1477200] ; R&D Program of Shanghai Municipal Science and Technology Commission[SKLDR-2022-LH-09] ; Fund of State Key Laboratory of Drug Research |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001514125400001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318642]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Hou, Qiongqiong; He, Yang; Aisa, Haji Akber |
| 作者单位 | 1.Xinjiang Med Univ, Sch Pharm, Urumqi 830054, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plants, Urumqi 830011, Peoples R China 6.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Wenjiao,Sun, Haiguo,Ji, Jing,et al. Identification of Cannabigerol-Derived Dual CB2 Receptor Agonists and TRPM8 Antagonists with Anti-Inflammatory and Analgesic Activities[J]. JOURNAL OF MEDICINAL CHEMISTRY,2025,68(13):13335-13357. |
| APA | Yang, Wenjiao.,Sun, Haiguo.,Ji, Jing.,Chen, Hai.,Cheng, Jiaxin.,...&Aisa, Haji Akber.(2025).Identification of Cannabigerol-Derived Dual CB2 Receptor Agonists and TRPM8 Antagonists with Anti-Inflammatory and Analgesic Activities.JOURNAL OF MEDICINAL CHEMISTRY,68(13),13335-13357. |
| MLA | Yang, Wenjiao,et al."Identification of Cannabigerol-Derived Dual CB2 Receptor Agonists and TRPM8 Antagonists with Anti-Inflammatory and Analgesic Activities".JOURNAL OF MEDICINAL CHEMISTRY 68.13(2025):13335-13357. |
入库方式： OAI收割
来源：上海药物研究所
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