• 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

探索苯乙醇胺N-甲基转移酶的活性位点：3-烷基-7-取代-1,2,3,4-四氢异喹啉抑制剂

Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors.

作者信息

Grunewald Gary L, Romero F Anthony, Chieu Alex D, Fincham Kelcie J, Bhat Seema R, Criscione Kevin R

机构信息

Department of Medicinal Chemistry, School of Pharmacy, Malott Hall, Room 4060, University of Kansas, 1251 Wescoe Hall Dr., Lawrence, KS 66045-7582, USA.

出版信息

Bioorg Med Chem. 2005 Feb 15;13(4):1261-73. doi: 10.1016/j.bmc.2004.11.015.

DOI:10.1016/j.bmc.2004.11.015
PMID:15670935
Abstract

A series of 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinolines was synthesized and these compounds were evaluated for their PNMT inhibitory potency and affinity for the alpha2-adrenoceptor. 7-Nitro-, 7-bromo-, 7-aminosulfonyl-, or 7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs that possess a 3-alkyl substituent that is longer than a methyl group showed decreased PNMT inhibitory potency, except for 3-propyl-7-aminosulfonyl-THIQ, which displayed excellent PNMT inhibitory potency. The rank order for selectivity (PNMT vs the alpha2-adrenoceptor) is 3-alkyl-7-aminosulfonyl-THIQs congruent with 3-alkyl-7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs>3-alkyl-7-nitro-THIQs>3-alkyl-7-bromo-THIQs.

摘要

合成了一系列3-烷基-7-取代的1,2,3,4-四氢异喹啉，并对这些化合物的去甲肾上腺素甲基转移酶（PNMT）抑制活性以及对α2-肾上腺素能受体的亲和力进行了评估。具有比甲基长的3-烷基取代基的7-硝基、7-溴、7-氨基磺酰基或7-N-2,2,2-三氟乙基氨基磺酰基-四氢异喹啉（THIQs）显示出去甲肾上腺素甲基转移酶（PNMT）抑制活性降低，但3-丙基-7-氨基磺酰基-四氢异喹啉（THIQ）除外，其显示出优异的去甲肾上腺素甲基转移酶（PNMT）抑制活性。选择性（去甲肾上腺素甲基转移酶（PNMT）与α2-肾上腺素能受体）的排序为：3-烷基-7-氨基磺酰基-四氢异喹啉（THIQs）与3-烷基-7-N-2,2,2-三氟乙基氨基磺酰基-四氢异喹啉（THIQs）相当>3-烷基-7-硝基-四氢异喹啉（THIQs）>3-烷基-7-溴-四氢异喹啉（THIQs）。

相似文献

1
Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors.探索苯乙醇胺N-甲基转移酶的活性位点：3-烷基-7-取代-1,2,3,4-四氢异喹啉抑制剂
Bioorg Med Chem. 2005 Feb 15;13(4):1261-73. doi: 10.1016/j.bmc.2004.11.015.
2
3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-adrenoceptor.3,7-二取代-1,2,3,4-四氢异喹啉作为苯乙醇胺N-甲基转移酶的抑制剂，相对于α2-肾上腺素能受体显示出显著的效力和选择性。
J Med Chem. 1999 Jun 3;42(11):1982-90. doi: 10.1021/jm9807252.
3
Synthesis, biochemical evaluation, and classical and three-dimensional quantitative structure-activity relationship studies of 7-substituted-1,2,3,4-tetrahydroisoquinolines and their relative affinities toward phenylethanolamine N-methyltransferase and the alpha2-adrenoceptor.7-取代-1,2,3,4-四氢异喹啉的合成、生化评价以及经典和三维定量构效关系研究及其对苯乙醇胺N-甲基转移酶和α2-肾上腺素能受体的相对亲和力
J Med Chem. 1999 Jan 14;42(1):118-34. doi: 10.1021/jm980429p.
4
Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inhibition of phenylethanolamine N-methyltransferase vs the alpha 2-adrenoceptor.研究酸性氢在赋予7-（氨磺酰基）-1,2,3,4-四氢异喹啉（SK&F 29661）对苯乙醇胺N-甲基转移酶与α2-肾上腺素能受体抑制作用的选择性方面的作用。
J Med Chem. 1997 Dec 5;40(25):3997-4005. doi: 10.1021/jm960235e.
5
Inhibitors of phenylethanolamine N-methyltransferase that are predicted to penetrate the blood-brain barrier: design, synthesis, and evaluation of 3-fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines that possess low affinity toward the alpha2-adrenoceptor.预测可穿透血脑屏障的苯乙醇胺N-甲基转移酶抑制剂：对α2-肾上腺素能受体亲和力低的3-氟甲基-7-(N-取代氨磺酰基)-1,2,3,4-四氢异喹啉的设计、合成及评价
J Med Chem. 2004 Aug 26;47(18):4483-93. doi: 10.1021/jm0400653.
6
Synthesis and evaluation of 3-trifluoromethyl-7-substituted-1,2,3, 4-tetrahydroisoquinolines as selective inhibitors of phenylethanolamine N-methyltransferase versus the alpha(2)-adrenoceptor.3-三氟甲基-7-取代-1,2,3,4-四氢异喹啉作为苯乙醇胺N-甲基转移酶相对于α(2)-肾上腺素能受体的选择性抑制剂的合成与评价
J Med Chem. 1999 Aug 26;42(17):3315-23. doi: 10.1021/jm980734a.
7
3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display remarkable potency and selectivity.3-羟甲基-7-(N-取代氨磺酰基)-1,2,3,4-四氢异喹啉对苯乙醇胺N-甲基转移酶具有显著的效力和选择性的抑制剂。
J Med Chem. 2005 Jan 13;48(1):134-40. doi: 10.1021/jm049368n.
8
Enantiospecific synthesis of 3-fluoromethyl-, 3-hydroxymethyl-, and 3-chloromethyl-1,2,3,4-tetrahydroisoquinolines as selective inhibitors of phenylethanolamine N-methyltransferase versus the alpha(2)-adrenoceptor.对映体特异性合成3-氟甲基-、3-羟甲基-和3-氯甲基-1,2,3,4-四氢异喹啉，作为苯乙醇胺N-甲基转移酶相对于α(2)-肾上腺素能受体的选择性抑制剂。
J Med Chem. 1999 Oct 21;42(21):4351-61. doi: 10.1021/jm990086a.
9
Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines.用3-羟乙基-和3-羟丙基-7-取代-1,2,3,4-四氢异喹啉探索苯乙醇胺N-甲基转移酶的活性位点。
Bioorg Med Chem Lett. 2005 Feb 15;15(4):1143-7. doi: 10.1016/j.bmcl.2004.12.013.
10
Effects of a 3-alkyl-, 4-hydroxy- and/or 8-aromatic-substituent on the phenylethanolamine N-methyltransferase inhibitor potency and alpha2-adrenoceptor affinity of 2,3,4,5-tetrahydro-1H-2-benzazepines.3-烷基、4-羟基和/或8-芳基取代基对2,3,4,5-四氢-1H-2-苯并氮杂䓬类苯乙醇胺N-甲基转移酶抑制剂活性及α2-肾上腺素能受体亲和力的影响
Bioorg Med Chem. 2001 Aug;9(8):1957-65. doi: 10.1016/s0968-0896(01)00112-2.

引用本文的文献

1
Molecular recognition of physiological substrate noradrenaline by the adrenaline-synthesizing enzyme PNMT and factors influencing its methyltransferase activity.肾上腺素合成酶PNMT对生理底物去甲肾上腺素的分子识别及其甲基转移酶活性的影响因素。
Biochem J. 2009 Aug 27;422(3):463-71. doi: 10.1042/BJ20090702.
2
Synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines and comparison with their isosteric 1,2,3,4-tetrahydroisoquinolines as inhibitors of phenylethanolamine N-methyltransferase.4,5,6,7-四氢噻吩并[3,2-c]吡啶的合成及其作为苯乙醇胺N-甲基转移酶抑制剂与等排体1,2,3,4-四氢异喹啉的比较。
Bioorg Med Chem. 2008 Jan 1;16(1):542-59. doi: 10.1016/j.bmc.2007.08.066. Epub 2007 Oct 11.
3
Application of the Goldilocks effect to the design of potent and selective inhibitors of phenylethanolamine N-methyltransferase: balancing pKa and steric effects in the optimization of 3-methyl-1,2,3,4-tetrahydroisoquinoline inhibitors by beta-fluorination.
“金发姑娘效应”在苯乙醇胺N-甲基转移酶强效和选择性抑制剂设计中的应用：通过β-氟化优化3-甲基-1,2,3,4-四氢异喹啉抑制剂时平衡pKa和空间效应
J Med Chem. 2006 May 18;49(10):2939-52. doi: 10.1021/jm051262k.