• 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

一系列取代的2-(1H-呋喃并[2,3-g]吲唑-1-基)乙胺衍生物作为5-HT2C受体激动剂的合成及构效关系

Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists.

作者信息

Shimada Itsuro, Maeno Kyoichi, Kazuta Ken-ichi, Kubota Hideki, Kimizuka Tetsuya, Kimura Yasuharu, Hatanaka Ken-ichi, Naitou Yuki, Wanibuchi Fumikazu, Sakamoto Shuichi, Tsukamoto Shin-ichi

机构信息

Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

出版信息

Bioorg Med Chem. 2008 Feb 15;16(4):1966-82. doi: 10.1016/j.bmc.2007.10.100. Epub 2007 Nov 4.

DOI:10.1016/j.bmc.2007.10.100
PMID:18035544
Abstract

A series of novel indazole derivatives were synthesized, and their structure-activity relationships examined in order to identify potent and selective 5-HT2C receptor agonists. Among these compounds, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348) had a good in vitro profile, that is, high agonistic activity to the human 5-HT2C receptor subtype (EC50 = 1.0 nM) and high selectivity over 5-HT2A receptors. This compound was also effective in a rat penile erection model when administered p.o.

摘要

合成了一系列新型吲唑衍生物，并研究了它们的构效关系，以确定强效且选择性的5-HT2C受体激动剂。在这些化合物中，(S)-2-(7-乙基-1H-呋喃并[2,3-g]吲唑-1-基)-1-甲胺(YM348)具有良好的体外活性，即对人5-HT2C受体亚型具有高激动活性(EC50 = 1.0 nM)，且对5-HT2A受体具有高选择性。该化合物经口服给药时，在大鼠阴茎勃起模型中也有效。

相似文献

1
Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists.一系列取代的2-(1H-呋喃并[2,3-g]吲唑-1-基)乙胺衍生物作为5-HT2C受体激动剂的合成及构效关系
Bioorg Med Chem. 2008 Feb 15;16(4):1966-82. doi: 10.1016/j.bmc.2007.10.100. Epub 2007 Nov 4.
2
Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists.一系列作为5-羟色胺2C受体激动剂的苯并氮杂卓衍生物的合成及构效关系
Bioorg Med Chem. 2008 Mar 15;16(6):3309-20. doi: 10.1016/j.bmc.2007.12.009. Epub 2007 Dec 8.
3
5-HT(2C) receptor activation is a common mechanism on proerectile effects of apomorphine, oxytocin and melanotan-II in rats.5-羟色胺（2C）受体激活是阿扑吗啡、催产素和黑素皮质素-Ⅱ对大鼠勃起作用的共同机制。
Eur J Pharmacol. 2008 Jul 28;589(1-3):157-62. doi: 10.1016/j.ejphar.2008.05.022. Epub 2008 May 24.
4
Thermogenic effect of YM348, a novel 5-HT2C-receptor agonist, in rats.新型5-HT2C受体激动剂YM348对大鼠的产热作用。
J Pharm Pharmacol. 2004 Dec;56(12):1551-6. doi: 10.1211/0022357044841.
5
Characterization of intracavernous pressure increase induced by Ym348, a novel 5-HT2C receptor agonist, in anesthetized rats.新型5-HT2C受体激动剂Ym348诱导麻醉大鼠海绵体内压力升高的特征
J Urol. 2006 May;175(5):1953-7. doi: 10.1016/S0022-5347(05)00920-1.
6
Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methylethylamines. Improved therapeutics for obsessive compulsive disorder.5HT2C受体的新型激动剂。取代的2-(吲哚-1-基)-1-甲基乙胺和2-(茚并[1,2-b]吡咯-1-基)-1-甲基乙胺的合成及生物学评价。用于强迫症的改良疗法。
J Med Chem. 1997 Aug 15;40(17):2762-9. doi: 10.1021/jm970030l.
7
Antiobesity effect of YM348, a novel 5-HT2C receptor agonist, in Zucker rats.新型5-HT2C受体激动剂YM348对肥胖Zucker大鼠的抗肥胖作用
Brain Res. 2004 Jun 18;1011(2):221-7. doi: 10.1016/j.brainres.2004.03.032.
8
The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT2C receptor agonist.一种用作5-HT2C受体激动剂的三环单氮支架的设计与合成。
Bioorg Med Chem Lett. 2006 Aug 1;16(15):4130-4. doi: 10.1016/j.bmcl.2006.04.070. Epub 2006 Jun 5.
9
Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C receptor agonist.新型强效口服活性5-HT2C受体激动剂YM348的药理学特性
Eur J Pharmacol. 2004 Jan 1;483(1):37-43. doi: 10.1016/j.ejphar.2003.10.004.
10
Identification of 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT2C receptor agonists.鉴定4-甲基-1,2,3,4,10,10a-六氢吡嗪并[1,2-a]吲哚为5-HT2C受体激动剂。
Bioorg Med Chem Lett. 2005 Aug 1;15(15):3604-8. doi: 10.1016/j.bmcl.2005.05.074.

引用本文的文献

1
Rapid Assembly of Tetrasubstituted Furans via Pummerer-Type Rearrangement.通过 Pummerer 重排反应快速合成四取代呋喃。
J Am Chem Soc. 2021 Jan 20;143(2):1216-1223. doi: 10.1021/jacs.0c12194. Epub 2021 Jan 5.
2
Fast and accurate prediction of the regioselectivity of electrophilic aromatic substitution reactions.亲电芳香取代反应区域选择性的快速准确预测。
Chem Sci. 2017 Nov 13;9(3):660-665. doi: 10.1039/c7sc04156j. eCollection 2018 Jan 21.
3
De Novo Synthesis of Benzannelated Heterocycles.苯并稠合杂环的从头合成。
Chemistry. 2018 Jan 26;24(6):1455-1458. doi: 10.1002/chem.201705662. Epub 2017 Dec 22.
4
Toward biophysical probes for the 5-HT3 receptor: structure-activity relationship study of granisetron derivatives.针对 5-HT3 受体的生物物理探针：格拉司琼衍生物的构效关系研究。
J Med Chem. 2010 Mar 11;53(5):2324-8. doi: 10.1021/jm901827x.
5
Unprecedented rearrangement of 2-(2-aminoethyl)-1-aryl-3,4-dihydropyrazino[1,2-b]indazole-2-ium 6-oxides to 2,3-dihydro-1H-imidazo[1,2-b]indazoles.2-(2-氨基乙基)-1-芳基-3,4-二氢吡嗪并[1,2-b]吲哚-2-鎓 6-氧化物的空前重排为 2,3-二氢-1H-咪唑并[1,2-b]吲哚。
J Org Chem. 2010 Jan 15;75(2):502-5. doi: 10.1021/jo902301x.
6
Remarkably efficient synthesis of 2H-indazole 1-oxides and 2H-indazoles via tandem carbon-carbon followed by nitrogen-nitrogen bond formation.通过碳-碳串联反应随后形成氮-氮键，高效合成2H-吲唑-1-氧化物和2H-吲唑。
J Org Chem. 2008 Nov 21;73(22):9027-32. doi: 10.1021/jo8018895. Epub 2008 Oct 21.