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Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs. Discovery of Potent Analgesics for Neuropathic Pain

文献类型：期刊论文

作者Huang, Bin1,2; Zhang, Fengying1,2; Yu, Gang3; Song, Yan1,2; Wang, Xintong1,2; Wang, Meiliang3; Gong, Zehui3; Su, Ruibin3; Jia, Yanxing1,2
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2016-04-28
卷号59期号:8页码:3953-3963
ISSN号0022-2623
DOI10.1021/acs.jmedchem.6b00132
文献子类Article
英文摘要(-)-Incarvillateine (INCA) is the major antinociceptive component of Incarvillea sinensis, which has been used to treat rheumatism and relieve pain in traditional Chinese medicine. We have developed a concise and general synthetic approach for INCA, which enabled gram-scale asymmetric syntheses of (-)-INCA, (-)-incarvilline, (-)-isoincarvilline, and six other INCA analogues. The synthesis of isoincarvilline was reported for the first time. Three structurally simplified analogues of INCA were also synthesized. In vivo screening found that INCA and two structurally optimized analogues were efficacious hi preventing the acetic acid-induced writhing response. Moreover, their analgesic efficacy was demonstrated in formalin induced pain model. More importantly, administration of 20 or 40 mg/kg INCA and two structurally optimized analogues showed strong analgesic effects in spared nerve injury (SNI) model, and their effective doses were lower than the current gold standard, gabapentin (100 mg/kg in this model).
WOS关键词ALPHA-TRUXILLIC ACID ; INCARVILLEA-SINENSIS ; PHARMACOLOGICAL-TREATMENT ; DERIVATIVES ; ALKALOIDS ; INHIBITOR
资助项目National Natural Science Foundation of China[21290183] ; National Natural Science Foundation of China[21372017] ; National Natural Science Foundation of China[21572008] ; State Key Laboratory of Drug Research[00000000]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000375519900025
源URL[http://119.78.100.183/handle/2S10ELR8/276066]  
专题新药研究国家重点实验室
中科院受体结构与功能重点实验室
通讯作者Jia, Yanxing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China;
3.Beijing Inst Pharmacol & Toxicol, Beijing Key Lab Neuropsychopharmacol, State Key Lab Toxicol & Med Countermeasures, 27 Taiping Rd, Beijing 100850, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Bin,Zhang, Fengying,Yu, Gang,et al. Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs. Discovery of Potent Analgesics for Neuropathic Pain[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(8):3953-3963.
APA Huang, Bin.,Zhang, Fengying.,Yu, Gang.,Song, Yan.,Wang, Xintong.,...&Jia, Yanxing.(2016).Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs. Discovery of Potent Analgesics for Neuropathic Pain.JOURNAL OF MEDICINAL CHEMISTRY,59(8),3953-3963.
MLA Huang, Bin,et al."Gram Scale Syntheses of (-)-Incarvillateine and Its Analogs. Discovery of Potent Analgesics for Neuropathic Pain".JOURNAL OF MEDICINAL CHEMISTRY 59.8(2016):3953-3963.

入库方式： OAI收割

来源：上海药物研究所

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