• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

奥维诺醇6,14-桥的官能化。第3部分：18-和19-羟基取代奥维诺醇的制备及药理评价。

Functionalization of the 6,14-bridge of the orvinols. Part 3: preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols.

作者信息

Wu Huifang, Smith Trudy A, Huang Hongyan, Wang Jia Bei, Deschamps Jeffrey R, Coop Andrew

机构信息

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.

出版信息

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4829-31. doi: 10.1016/j.bmcl.2007.06.050. Epub 2007 Jun 20.

DOI:10.1016/j.bmcl.2007.06.050
PMID:17601735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2084076/
Abstract

The orvinols are a class of potent opioids which have been extensively studied, yet little is known about the effects of introducing substituents into the 18- and 19-positions. The etheno bridge of thevinone was hydroxylated to give both the 18- and 19-hydroxyl substituted thevinols. After 3-O-demethylation to the corresponding orvinols, binding and GTPgammaS functional assays indicated that hydroxyl substitution at the 18- and 19-positions differentially affects the mu opioid efficacy of orvinols.

摘要

奥维诺醇类是一类经过广泛研究的强效阿片类药物，但对于在18位和19位引入取代基的影响却知之甚少。将蒂巴因酮的乙烯桥羟基化，得到18位和19位羟基取代的奥维诺醇。在将其3-O-去甲基化转化为相应的奥维诺醇后，结合和GTPγS功能测定表明，18位和19位的羟基取代对奥维诺醇的μ阿片样物质效能有不同影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/ede0035e83bc/nihms28975f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/39ec51512d7f/nihms28975f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/dfa8b480e97a/nihms28975f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/a5ea827059ca/nihms28975f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/ede0035e83bc/nihms28975f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/39ec51512d7f/nihms28975f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/dfa8b480e97a/nihms28975f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/a5ea827059ca/nihms28975f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e879/2084076/ede0035e83bc/nihms28975f4.jpg

相似文献

1
Functionalization of the 6,14-bridge of the orvinols. Part 3: preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols.奥维诺醇6,14-桥的官能化。第3部分：18-和19-羟基取代奥维诺醇的制备及药理评价。
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4829-31. doi: 10.1016/j.bmcl.2007.06.050. Epub 2007 Jun 20.
2
Ring-constrained orvinols as analogs of buprenorphine: differences in opioid activity related to configuration of C(20) hydroxyl group.作为丁丙诺啡类似物的环约束奥维诺醇：与C(20)羟基构型相关的阿片样物质活性差异。
J Pharmacol Exp Ther. 1999 Dec;291(3):1093-9.
3
Functionalization of the 6,14-bridge of the orvinols. 2. Preparation of 18- and 19-hydroxyl-substituted thevinols and their treatment with benzyl bromide.奥维诺醇6,14-桥的官能化。2. 18-和19-羟基取代的酒石醇的制备及其与苄基溴的反应。
J Org Chem. 2005 Mar 4;70(5):1907-10. doi: 10.1021/jo048388u.
4
C(21)-fluorinated thevinol scaffold for opioid ligands. 21,21,21-Trifluoro-6-O-nororvinols: Design, synthesis and analgesic activity.用于阿片样物质配体的C(21)-氟化蒂巴因支架。21,21,21-三氟-6-O-去甲奥列文醇：设计、合成及镇痛活性。
Eur J Med Chem. 2023 Apr 5;252:115296. doi: 10.1016/j.ejmech.2023.115296. Epub 2023 Mar 22.
5
Synthesis and opioid activity of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines.手性 N-取代的 2,3,4,4a,5,6,7,7a-八氢-1H-苯并呋喃[3,2-e]异喹啉的合成及阿片样活性。
J Med Chem. 2010 Feb 11;53(3):1392-6. doi: 10.1021/jm901503e.
6
Probes for narcotic receptor mediated phenomena. 37. Synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of the ortho- and para-d-isomers.麻醉受体介导现象的探针。37. 最后一对氧化物桥连苯吗喃（邻位和对位β-异构体及其N-苯乙基类似物）的合成与阿片样物质结合亲和力，以及邻位和对位δ-异构体的N-苯乙基类似物的合成。
J Med Chem. 2008 Dec 25;51(24):7866-81. doi: 10.1021/jm800913d.
7
Synthesis, modeling, and pharmacological evaluation of UMB 425, a mixed μ agonist/δ antagonist opioid analgesic with reduced tolerance liabilities.UMB 425 的合成、建模和药理学评价，一种具有降低耐受性风险的混合 μ 激动剂/δ 拮抗剂阿片类镇痛药。
ACS Chem Neurosci. 2013 Sep 18;4(9):1256-66. doi: 10.1021/cn4000428. Epub 2013 Jun 11.
8
Activities of mixed NOP and mu-opioid receptor ligands.混合的孤啡肽（NOP）和μ-阿片受体配体的活性。
Br J Pharmacol. 2008 Feb;153(3):609-19. doi: 10.1038/sj.bjp.0707598. Epub 2007 Dec 3.
9
Stimulation of guanosine-5'-o-(3-[35S]thio)triphosphate binding in digitonin-permeabilized C6 rat glioma cells: evidence for an organized association of mu-opioid receptors and G protein.洋地黄皂苷通透的C6大鼠胶质瘤细胞中鸟苷-5'-O-(3-[35S]硫代)三磷酸结合的刺激：μ-阿片受体与G蛋白有序结合的证据
J Pharmacol Exp Ther. 2001 Jul;298(1):116-21.
10
Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants.传统型和截短型μ阿片受体剪接变体联合介导丁丙诺啡镇痛作用。
Synapse. 2016 Oct;70(10):395-407. doi: 10.1002/syn.21914. Epub 2016 Jul 12.

引用本文的文献

1
Diels-Alder Adducts of Morphinan-6,8-Dienes and Their Transformations.吗啡喃-6,8-二烯的 Diels-Alder 加合物及其转化。
Molecules. 2022 Apr 30;27(9):2863. doi: 10.3390/molecules27092863.

本文引用的文献

1
Thienorphine: receptor binding and behavioral effects in rhesus monkeys.噻诺啡：恒河猴体内的受体结合及行为效应
J Pharmacol Exp Ther. 2007 Apr;321(1):227-36. doi: 10.1124/jpet.106.113290. Epub 2007 Jan 12.
2
Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine.液体与片剂丁丙诺啡的药代动力学、生物利用度及阿片样物质效应
Drug Alcohol Depend. 2006 Mar 15;82(1):25-31. doi: 10.1016/j.drugalcdep.2005.08.005. Epub 2005 Sep 6.
3
Medications development: successes and challenges.药物研发：成功与挑战
Pharmacol Ther. 2005 Oct;108(1):94-108. doi: 10.1016/j.pharmthera.2005.06.010.
4
Major increases in opioid analgesic abuse in the United States: concerns and strategies.美国阿片类镇痛药滥用情况大幅增加：关注要点与应对策略
Drug Alcohol Depend. 2006 Feb 1;81(2):103-7. doi: 10.1016/j.drugalcdep.2005.05.009. Epub 2005 Jul 14.
5
Functionalization of the 6,14-bridge of the orvinols. 2. Preparation of 18- and 19-hydroxyl-substituted thevinols and their treatment with benzyl bromide.奥维诺醇6,14-桥的官能化。2. 18-和19-羟基取代的酒石醇的制备及其与苄基溴的反应。
J Org Chem. 2005 Mar 4;70(5):1907-10. doi: 10.1021/jo048388u.
6
Role of mPKCI, a novel mu-opioid receptor interactive protein, in receptor desensitization, phosphorylation, and morphine-induced analgesia.新型μ-阿片受体相互作用蛋白mPKCI在受体脱敏、磷酸化及吗啡诱导的镇痛中的作用
Mol Pharmacol. 2004 Nov;66(5):1285-92. doi: 10.1124/mol.66.5..
7
The orvinols and related opioids--high affinity ligands with diverse efficacy profiles.奥维诺类及相关阿片类药物——具有不同效应特征的高亲和力配体。
Curr Pharm Des. 2004;10(7):717-32. doi: 10.2174/1381612043453027.
8
Structural determinants of opioid activity in the orvinols and related structures: ethers of orvinol and isoorvinol.
J Med Chem. 2000 May 4;43(9):1852-7. doi: 10.1021/jm990951r.
9
Selected cysteine residues in transmembrane domains of mu-opioid receptor are critical for effects of sulfhydryl reagents.μ-阿片受体跨膜结构域中选定的半胱氨酸残基对巯基试剂的作用至关重要。
J Pharmacol Exp Ther. 2000 Apr;293(1):113-20.