• 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

5,6-二芳基吡嗪-2-酰胺衍生物的骨架跃迁、合成及构效关系：一类新型的CB1受体拮抗剂

Scaffold hopping, synthesis and structure-activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: a novel series of CB1 receptor antagonists.

作者信息

Boström Jonas, Berggren Kristina, Elebring Thomas, Greasley Peter J, Wilstermann Michael

机构信息

Lead Generation Department, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden.

出版信息

Bioorg Med Chem. 2007 Jun 15;15(12):4077-84. doi: 10.1016/j.bmc.2007.03.075. Epub 2007 Mar 30.

DOI:10.1016/j.bmc.2007.03.075
PMID:17433696
Abstract

A scaffold hopping approach has been exploited to design a novel class of cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis of shape-complementarity and synthetic feasibility the central fragment, a methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1 antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide derivatives are described. Several compounds showed antagonist potency below 10nM for the CB1 receptor.

摘要

一种基于骨架跃迁的方法已被用于设计一类新型的大麻素（CB1）受体拮抗剂，用于治疗肥胖症。基于形状互补性和合成可行性，利莫那班中的中心片段甲基吡唑被吡嗪所取代。本文描述了一系列新型5,6-二芳基吡嗪-2-酰胺衍生物的合成及其对CB1的拮抗活性。几种化合物对CB1受体显示出低于10nM的拮抗效力。

相似文献

1
Scaffold hopping, synthesis and structure-activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: a novel series of CB1 receptor antagonists.5,6-二芳基吡嗪-2-酰胺衍生物的骨架跃迁、合成及构效关系：一类新型的CB1受体拮抗剂
Bioorg Med Chem. 2007 Jun 15;15(12):4077-84. doi: 10.1016/j.bmc.2007.03.075. Epub 2007 Mar 30.
2
Novel thioamide derivatives as neutral CB1 receptor antagonists.新型硫代酰胺衍生物作为中性 CB1 受体拮抗剂。
Bioorg Med Chem Lett. 2010 Jan 15;20(2):479-82. doi: 10.1016/j.bmcl.2009.11.125. Epub 2009 Nov 27.
3
Synthesis and pharmacological evaluation of novel octahydro-1H-pyrido[1,2-a]pyrazine as mu-opioid receptor antagonists.新型八氢-1H-吡啶并[1,2-a]吡嗪作为μ-阿片受体拮抗剂的合成与药理学评价
J Med Chem. 2006 Dec 14;49(25):7290-306. doi: 10.1021/jm0604878.
4
Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands.作为CB1大麻素受体配体的哌嗪类似物的设计、合成及生物学评价
Bioorg Med Chem. 2008 Apr 1;16(7):4035-51. doi: 10.1016/j.bmc.2008.01.023. Epub 2008 Jan 19.
5
Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists.二芳基咪唑基恶二唑和噻二唑衍生物作为大麻素CB1受体拮抗剂
Bioorg Med Chem Lett. 2009 Jan 1;19(1):142-5. doi: 10.1016/j.bmcl.2008.10.130. Epub 2008 Nov 5.
6
Keynote review: Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists.
Drug Discov Today. 2005 May 15;10(10):693-702. doi: 10.1016/S1359-6446(05)03427-6.
7
Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity.新型3,4-二芳基吡唑啉类化合物作为亲脂性较低的强效大麻素CB1受体拮抗剂。
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4794-8. doi: 10.1016/j.bmcl.2005.07.054.
8
Chemical and biological investigation of cyclopropyl containing diaryl-pyrazole-3-carboxamides as novel and potent cannabinoid type 1 receptor antagonists.含环丙基的二芳基吡唑-3-甲酰胺作为新型强效大麻素1型受体拮抗剂的化学与生物学研究
J Med Chem. 2009 Jul 23;52(14):4329-37. doi: 10.1021/jm900179y.
9
Biarylpyrazolyl oxadiazole as potent, selective, orally bioavailable cannabinoid-1 receptor antagonists for the treatment of obesity.联芳基吡唑基恶二唑作为强效、选择性、口服生物可利用的大麻素-1受体拮抗剂用于治疗肥胖症。
J Med Chem. 2008 Nov 27;51(22):7216-33. doi: 10.1021/jm800843r.
10
Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists.1,2,4-三唑啉酮作为CB1受体选择性拮抗剂的设计、合成、生物学评价及比较对接研究
Eur J Med Chem. 2014 Mar 3;74:73-84. doi: 10.1016/j.ejmech.2013.12.018. Epub 2013 Dec 31.

引用本文的文献

1
Scaffold Hopping and Structural Modification of NSC 663284: Discovery of Potent (Non)Halogenated Aminobenzoquinones.NSC 663284的骨架跃迁与结构修饰：新型（非）卤代氨基苯醌的发现
Biomedicines. 2023 Dec 24;12(1):50. doi: 10.3390/biomedicines12010050.
2
I-Catalyzed Carbonylation of α-Methylene Ketones to Synthesize 1,2-Diaryl Diketones and Antiviral Quinoxalines in One Pot.碘催化α-亚甲基酮的羰基化反应一锅法合成1,2-二芳基二酮和抗病毒喹喔啉类化合物
ACS Omega. 2021 Dec 21;7(1):1380-1394. doi: 10.1021/acsomega.1c06017. eCollection 2022 Jan 11.
3
Shape-Restrained Modeling of Protein-Small-Molecule Complexes with High Ambiguity Driven DOCKing.
基于高模糊度驱动对接的蛋白质-小分子复合物的形状约束建模。
J Chem Inf Model. 2021 Sep 27;61(9):4807-4818. doi: 10.1021/acs.jcim.1c00796. Epub 2021 Aug 26.
4
Ammonium chloride-catalyzed green multicomponent synthesis of dihydropyrazine and tetrahydrodiazepine derivatives "on water".氯化铵催化的水相中绿色多组分合成二氢吡嗪和四氢哒嗪衍生物。
Mol Divers. 2019 Aug;23(3):585-592. doi: 10.1007/s11030-018-9893-5. Epub 2018 Nov 21.
5
Advances in the Development of Shape Similarity Methods and Their Application in Drug Discovery.形状相似性方法的发展进展及其在药物发现中的应用
Front Chem. 2018 Jul 25;6:315. doi: 10.3389/fchem.2018.00315. eCollection 2018.
6
Shape similarity guided pose prediction: lessons from D3R Grand Challenge 3.形状相似性引导的姿势预测：D3R 大挑战 3 的经验教训。
J Comput Aided Mol Des. 2019 Jan;33(1):47-59. doi: 10.1007/s10822-018-0142-x. Epub 2018 Aug 6.
7
The comparison of automated clustering algorithms for resampling representative conformer ensembles with RMSD matrix.用于通过均方根偏差（RMSD）矩阵对代表性构象异构体集合进行重采样的自动聚类算法比较。
J Cheminform. 2017 Mar 23;9(1):21. doi: 10.1186/s13321-017-0208-0.
8
Classification of scaffold-hopping approaches.支架跳跃方法的分类。
Drug Discov Today. 2012 Apr;17(7-8):310-24. doi: 10.1016/j.drudis.2011.10.024. Epub 2011 Oct 26.
9
Identification of a chemical probe for NAADP by virtual screening.通过虚拟筛选鉴定NAADP的化学探针
Nat Chem Biol. 2009 Apr;5(4):220-6. doi: 10.1038/nchembio.150. Epub 2009 Feb 22.