• 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

作为抗克氏锥虫药物的癌症药物临床候选替匹法尼的异喹啉基类似物。

Isoquinoline-based analogs of the cancer drug clinical candidate tipifarnib as anti-Trypanosoma cruzi agents.

作者信息

Chennamaneni Naveen Kumar, Arif Jenifer, Buckner Frederick S, Gelb Michael H

机构信息

Department of Chemistry, University of Washington, Seattle, WA 98195, USA.

出版信息

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6582-4. doi: 10.1016/j.bmcl.2009.10.029. Epub 2009 Oct 13.

DOI:10.1016/j.bmcl.2009.10.029
PMID:19875282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2783978/
Abstract

We developed a synthetic route to prepare isoquinoline analogs of the cancer drug clinical candidate tipifarnib. We show that these compounds kill Trypanosoma cruzi amastigotes grown in mammalian host cells at concentrations in the low nanomolar range. These isoquinolines represent new leads for the development of drugs to treat Chagas disease.

摘要

我们开发了一条合成路线来制备癌症药物临床候选药物替匹法尼的异喹啉类似物。我们发现这些化合物能够在低纳摩尔浓度下杀死在哺乳动物宿主细胞中生长的克氏锥虫无鞭毛体。这些异喹啉代表了开发治疗恰加斯病药物的新先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/be9a7bc776c9/nihms156366f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/d85f17c85d82/nihms156366f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/9f09ef763228/nihms156366f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/2f431a968022/nihms156366f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/f299084c9c44/nihms156366f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/be9a7bc776c9/nihms156366f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/d85f17c85d82/nihms156366f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/9f09ef763228/nihms156366f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/2f431a968022/nihms156366f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/f299084c9c44/nihms156366f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471b/2783978/be9a7bc776c9/nihms156366f5.jpg

相似文献

1
Isoquinoline-based analogs of the cancer drug clinical candidate tipifarnib as anti-Trypanosoma cruzi agents.作为抗克氏锥虫药物的癌症药物临床候选替匹法尼的异喹啉基类似物。
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6582-4. doi: 10.1016/j.bmcl.2009.10.029. Epub 2009 Oct 13.
2
Second generation analogues of the cancer drug clinical candidate tipifarnib for anti-Chagas disease drug discovery.用于抗恰加斯病药物发现的癌症药物临床候选物替匹法尼的第二代类似物。
J Med Chem. 2010 May 27;53(10):3887-98. doi: 10.1021/jm9013136.
3
Synthesis, in vitro antitrypanosomal and antibacterial activity of phenoxy, phenylthio or benzyloxy substituted quinolones.苯氧基、苯硫基或苄氧基取代喹诺酮的合成、体外抗锥虫和抗菌活性。
Bioorg Med Chem Lett. 2009 Feb 1;19(3):986-9. doi: 10.1016/j.bmcl.2008.11.078. Epub 2008 Nov 24.
4
Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib.从替匹法尼衍生的抗恰加斯病先导化合物的药理学特征、结构研究和体内活性。
Antimicrob Agents Chemother. 2012 Sep;56(9):4914-21. doi: 10.1128/AAC.06244-11. Epub 2012 Jul 9.
5
Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi.合成新型奎宁类似物并评估其对克氏锥虫的作用。
Future Med Chem. 2018 Feb;10(4):391-408. doi: 10.4155/fmc-2017-0184. Epub 2018 Jan 30.
6
Rational modification of a candidate cancer drug for use against Chagas disease.对一种候选抗癌药物进行合理改造以用于治疗恰加斯病。
J Med Chem. 2009 Mar 26;52(6):1639-47. doi: 10.1021/jm801313t.
7
Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi.天然胡椒碱及其衍生物对克氏锥虫前鞭毛体和无鞭毛体的毒性作用。
Bioorg Med Chem Lett. 2004 Jul 5;14(13):3555-8. doi: 10.1016/j.bmcl.2004.04.019.
8
Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease.合成、结构-活性关系和吡唑-咪唑啉和新吡唑-四氢嘧啶杂合作为潜在的治疗恰加斯病的化疗药物的杀锥虫活性。
Eur J Med Chem. 2019 Nov 15;182:111610. doi: 10.1016/j.ejmech.2019.111610. Epub 2019 Aug 10.
9
A structure-based approach towards the identification of novel antichagasic compounds: carbonic anhydrase inhibitors.基于结构的新型抗恰加斯病化合物的筛选方法：碳酸酐酶抑制剂。
J Enzyme Inhib Med Chem. 2020 Dec;35(1):21-30. doi: 10.1080/14756366.2019.1677638.
10
New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms.1,4-萘醌新型环氧化衍生物及其对抗 T. cruzi 无鞭毛体形式的评价。
Bioorg Med Chem. 2012 Aug 15;20(16):4995-5000. doi: 10.1016/j.bmc.2012.06.027. Epub 2012 Jun 21.

引用本文的文献

1
A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.癌症的新型克星：原生动物抗肿瘤特性的最新研究
Front Cell Infect Microbiol. 2024 Jan 11;13:1325144. doi: 10.3389/fcimb.2023.1325144. eCollection 2023.
2
Crystal Structure and Hirshfeld Surface Analysis of Acetoacetanilide Based Reaction Products.乙酰乙酰苯胺基反应产物的晶体结构和 Hirshfeld 表面分析。
Molecules. 2020 May 9;25(9):2235. doi: 10.3390/molecules25092235.
3
N-Substituted Auxiliaries for Aerobic Dehydrogenation of Tetrahydro-isoquinoline: A Theory-Guided Photo-Catalytic Design.

本文引用的文献

1
Rational modification of a candidate cancer drug for use against Chagas disease.对一种候选抗癌药物进行合理改造以用于治疗恰加斯病。
J Med Chem. 2009 Mar 26;52(6):1639-47. doi: 10.1021/jm801313t.
2
The protein farnesyltransferase inhibitor Tipifarnib as a new lead for the development of drugs against Chagas disease.蛋白质法尼基转移酶抑制剂替匹法尼布作为开发抗恰加斯病药物的新先导物。
J Med Chem. 2005 Aug 25;48(17):5415-8. doi: 10.1021/jm050441z.
3
Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase.
N-取代助剂在四氢异喹啉有氧脱氢反应中的应用：理论指导下的光催化设计。
Sci Rep. 2019 Aug 2;9(1):11280. doi: 10.1038/s41598-019-47735-y.
4
Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of "Hit-To-Lead" Phase.恰加斯病的合成药物化学：处于“从活性分子到先导化合物”阶段末期的化合物
Pharmaceuticals (Basel). 2010 Mar 25;3(4):810-838. doi: 10.3390/ph3040810.
5
Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51.靶向克氏锥虫CYP51的基于N-吲哚氧基吡啶基-4-氨基丙基的抑制剂的结合模式和效力
J Med Chem. 2014 Dec 11;57(23):10162-75. doi: 10.1021/jm501568b. Epub 2014 Nov 25.
6
Drug strategies targeting CYP51 in neglected tropical diseases.针对被忽视热带病中细胞色素P450 51（CYP51）的药物策略。
Chem Rev. 2014 Nov 26;114(22):11242-71. doi: 10.1021/cr5003134. Epub 2014 Oct 22.
7
4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.基于4-氨基吡啶基的CYP51抑制剂作为抗克氏锥虫药物先导物，具有改善的药代动力学特征和体内效力。
J Med Chem. 2014 Aug 28;57(16):6989-7005. doi: 10.1021/jm500448u. Epub 2014 Aug 19.
8
Trypanocidal activity of marine natural products.海洋天然产物的抗锥虫活性。
Mar Drugs. 2013 Oct 22;11(10):4058-82. doi: 10.3390/md11104058.
9
Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target.克氏锥虫半胱氨酸蛋白酶抑制剂的化学-生物学特性研究揭示了第二个靶标和一个哺乳动物的脱靶效应。
Beilstein J Org Chem. 2013;9:15-25. doi: 10.3762/bjoc.9.3. Epub 2013 Jan 4.
10
Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51.针对克氏锥虫 CYP51 的不同抑制剂化学型。
PLoS Negl Trop Dis. 2012;6(7):e1736. doi: 10.1371/journal.pntd.0001736. Epub 2012 Jul 31.
利用表达β-半乳糖苷酶的寄生虫筛选抗克氏锥虫活性药物的高效技术。
Antimicrob Agents Chemother. 1996 Nov;40(11):2592-7. doi: 10.1128/AAC.40.11.2592.
4
Cure of short- and long-term experimental Chagas' disease using D0870.使用D0870治愈短期和长期实验性恰加斯病。
Science. 1996 Aug 16;273(5277):969-71. doi: 10.1126/science.273.5277.969.