Synthesis and evaluation of kappa-opioid receptor agonistic activity and antinociceptive effect of novel morphine analogues, 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine with substituted o-, m- and p-amino group

doi:10.1007/s00044-010-9471-6

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	Synthesis and evaluation of kappa-opioid receptor agonistic activity and antinociceptive effect of novel morphine analogues, 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine with substituted o-, m- and p-amino group
	Qi, Hong 2; Li, Wei 3; Qiu, Yu 2; Cui, Yong-yao 2; Ma, Jian 2; Gao, Xiao-ling 2; Zeng, Yi-bin 3; Yang, Jie 3; Tang, Yun 4; Wang, Xing-hai 3
刊名	MEDICINAL CHEMISTRY RESEARCH
	2011-11
卷号	20 期号:8 页码:1364-1370
关键词	kappa-Opioid receptor Opioid agonist Antinociception
ISSN号	1054-2523
DOI	10.1007/s00044-010-9471-6
文献子类	Article
英文摘要	7 alpha-Phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine is an analogue of morphine but with much weaker affinity and efficacy to opioid receptors. Three compounds with o-, m- and p-amino substitution on its 7 alpha-phenyl group were designed and synthesized to evaluate their kappa-opioid receptor agonistic activity and antinociceptive effect. The introduction of amino group greatly increased the binding activity to kappa-opioid receptor but only compound with p-substitution showed agonistic activity with potency similar to the marketed kappa agonist butorphanol. In vivo antinociceptive test showed that compound with p-amino substitution displayed highest antinociceptive activity while compounds with o-, m-amino substitution showed partial or little analgesia effects. All these data indicate that p-amino substitution conferred kappa agonist activity, suggesting that 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaines with a p-amino substitution may contain a novel pharmacophore component and could be considered as a leading compound for novel antinociceptive agents.
资助项目	National Natural Science foundation of China[30672442] ; National Great Basic Science Project[2010CB529806] ; Shanghai Municipal Commission of Education Foundation[05BZ14] ; Fudan University[00000000] ; Shanghai Natural Science Foundation[08ZR1401500] ; Ministry of Education of China[20070246088]
WOS关键词	MOLECULAR-REARRANGEMENTS ; THEBAINE GROUP ; ANALGESICS ; 6,14-ENDO-ETHENOTETRAHYDROTHEBAINE ; INHIBITION ; ORVINOLS ; ALCOHOLS ; PEPTIDE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	BIRKHAUSER BOSTON INC
WOS记录号	WOS:000295577000029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278361]
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	Qiu, Yu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol, Inst Med Sci, Shanghai 200025, Peoples R China; 3.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China; 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Qi, Hong,Li, Wei,Qiu, Yu,et al. Synthesis and evaluation of kappa-opioid receptor agonistic activity and antinociceptive effect of novel morphine analogues, 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine with substituted o-, m- and p-amino group[J]. MEDICINAL CHEMISTRY RESEARCH,2011,20(8):1364-1370.
APA	Qi, Hong.,Li, Wei.,Qiu, Yu.,Cui, Yong-yao.,Ma, Jian.,...&Chen, Hong-zhuan.(2011).Synthesis and evaluation of kappa-opioid receptor agonistic activity and antinociceptive effect of novel morphine analogues, 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine with substituted o-, m- and p-amino group.MEDICINAL CHEMISTRY RESEARCH,20(8),1364-1370.
MLA	Qi, Hong,et al."Synthesis and evaluation of kappa-opioid receptor agonistic activity and antinociceptive effect of novel morphine analogues, 7 alpha-phenyl-6 alpha,14 alpha-endo-etheno-tetrahydrothebaine with substituted o-, m- and p-amino group".MEDICINAL CHEMISTRY RESEARCH 20.8(2011):1364-1370.