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SLL-627 Is a Highly Selective and Potent ? Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity

文献类型：期刊论文

作者Kong, Linghui8; Shu, Xuelian4,5,6,7; Tang, Siyuan8; Ye, Rongrong3; Sun, Huijiao8; Jiang, Shuang2; Li, Zixiang8; Chai, Jingrui5,6,7; Fang, Yun8; Lan, Yinjie8
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-07-28
页码16
ISSN号0022-2623
DOI10.1021/acs.jmedchem.2c00014
通讯作者Wang, Yujun(yjwang@simm.ac.cn) ; Li, Wei(wei-li@fudan.edu.cn) ; Liu, Jinggen(jgliu@simm.ac.cn) ; Shao, Liming(limingshao@fudan.edu.cn)
英文摘要Undue central nervous system (CNS) side effects including dysphoria and sedation remain to be a challenge for the development of kappa opioid receptor (KOR) agonists as effective and safe analgesics. On the basis of our previous work on morphinan-based KOR agonists, a series of 7 alpha-methyl-7 beta-substituted north-ebaine derivatives were designed, synthesized, and biologically assayed. Among others, compound 4a (SLL-627) has been identified as a highly selective and potent KOR agonist both in vitro and in vivo, and its molecular basis was also examined and discussed. Besides low liability to conditioned place aversion (CPA) test, treatment of SLL-627 was associated with a nonreduction in locomotor activity, compared to most of the other arylacetamide-or morphinan-based KOR agonists which generally exhibited apparently sedative effects. This unexpected finding provides new insights to dissociate analgesia from sedation for future discovery of innovative KOR agonists.
WOS关键词NALFURAFINE HYDROCHLORIDE ; NOCICEPTIN/ORPHANIN FQ ; HEMODIALYSIS-PATIENTS ; EFFICACY ; TOLERANCE ; DISCOVERY ; LIGANDS ; PAIN ; REARRANGEMENTS ; BUPRENORPHINE
资助项目Ministry of Science and Technology[2021ZD0202900] ; Ministry of Science and Technology[2021ZD0203500] ; National Natural Science Foundation of China[82030112] ; National Natural Science Foundation of China[81773710] ; Science and Technology Commis-sion of Shanghai Municipality[20ZR1468200] ; Shenzhen-Hong Kong Institute of Brain Science?[NYKFKT2019015] ; Shenzhen Fundamental Research Institutions
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000835249000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/301884]  
专题新药研究国家重点实验室
通讯作者Wang, Yujun; Li, Wei; Liu, Jinggen; Shao, Liming
作者单位1.Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
2.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China
3.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Collaborat Innovat Ctr Brain Sci, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
8.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Kong, Linghui,Shu, Xuelian,Tang, Siyuan,et al. SLL-627 Is a Highly Selective and Potent ? Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022:16.
APA Kong, Linghui.,Shu, Xuelian.,Tang, Siyuan.,Ye, Rongrong.,Sun, Huijiao.,...&Shao, Liming.(2022).SLL-627 Is a Highly Selective and Potent ? Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity.JOURNAL OF MEDICINAL CHEMISTRY,16.
MLA Kong, Linghui,et al."SLL-627 Is a Highly Selective and Potent ? Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity".JOURNAL OF MEDICINAL CHEMISTRY (2022):16.

入库方式： OAI收割

来源：上海药物研究所

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