• 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

吡唑并[3,4-]异喹啉的合成及激酶抑制活性。

Synthesis and Kinase Inhibitory Potencies of Pyrazolo[3,4-]isoquinolines.

机构信息

Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France.

Sorbonne Université, CNRS, Plateforme de Criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Protein Phosphorylation and Human Diseases Unit, Station Biologique, Place Georges Teissier, F-29688 Roscoff, France.

出版信息

Molecules. 2022 Aug 30;27(17):5578. doi: 10.3390/molecules27175578.

DOI:10.3390/molecules27175578
PMID:36080340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9457941/
Abstract

A new series of pyrazolo[3,4-]isoquinoline derivatives, diversely substituted at the 4- or 8-position, were synthesized. The results of the kinase inhibitory potency study demonstrated that the introduction of a bromine atom at the 8-position was detrimental to Haspin inhibition, while the introduction of an alkyl group at the 4-position led to a modification of the kinase inhibition profiles. Altogether, the results obtained demonstrated that new pyrazolo[3,4-]isoquinolines represent a novel family of kinase inhibitors with various selectivity profiles.

摘要

我们合成了一系列新型的吡唑并[3,4-]异喹啉衍生物，它们在 4-或 8-位上具有不同的取代基。激酶抑制活性研究结果表明，在 8-位引入溴原子会对 Haspin 的抑制产生不利影响，而在 4-位引入烷基则会改变激酶抑制谱。总的来说，这些结果表明，新型吡唑并[3,4-]异喹啉代表了一类具有不同选择性特征的新型激酶抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/f59b78ae1bf3/molecules-27-05578-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/1d70c1c02463/molecules-27-05578-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/ea1408d7e22e/molecules-27-05578-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/aae3b531faf3/molecules-27-05578-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/f59b78ae1bf3/molecules-27-05578-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/1d70c1c02463/molecules-27-05578-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/ea1408d7e22e/molecules-27-05578-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/aae3b531faf3/molecules-27-05578-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fa/9457941/f59b78ae1bf3/molecules-27-05578-g002.jpg

相似文献

1
Synthesis and Kinase Inhibitory Potencies of Pyrazolo[3,4-]isoquinolines.吡唑并[3,4-]异喹啉的合成及激酶抑制活性。
Molecules. 2022 Aug 30;27(17):5578. doi: 10.3390/molecules27175578.
2
Synthesis and biological evaluation of 1H-pyrrolo[3,2-g]isoquinolines.1H-吡咯并[3,2-g]异喹啉的合成与生物评价。
Bioorg Med Chem. 2024 Feb 15;100:117619. doi: 10.1016/j.bmc.2024.117619. Epub 2024 Feb 1.
3
Synthesis and biological evaluation of 7-substituted-1-(3-bromophenylamino)isoquinoline-4-carbonitriles as inhibitors of myosin light chain kinase and epidermal growth factor receptor.7-取代-1-(3-溴苯基氨基)异喹啉-4-甲腈的合成及作为肌球蛋白轻链激酶和表皮生长因子受体抑制剂的生物评价。
Bioorg Med Chem. 2011 Jan 1;19(1):429-39. doi: 10.1016/j.bmc.2010.11.007. Epub 2010 Nov 10.
4
Selective inhibition of cyclic AMP-dependent protein kinase by isoquinoline derivatives.异喹啉衍生物对环磷酸腺苷依赖性蛋白激酶的选择性抑制作用。
Biol Chem Hoppe Seyler. 1996 Jun;377(6):373-84. doi: 10.1515/bchm3.1996.377.6.373.
5
Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-kappaB activation.吡唑并[4,3-c]异喹啉类化合物作为 NF-κB 激活的潜在抑制剂。
Biochem Pharmacol. 2010 May 15;79(10):1462-72. doi: 10.1016/j.bcp.2010.01.007. Epub 2010 Jan 21.
6
Synthesis, EGFR Inhibition and Anti-cancer Activity of New 3,6-dimethyl-1-phenyl-4-(substituted-methoxy)pyrazolo[3,4-d] pyrimidine Derivatives.新型3,6-二甲基-1-苯基-4-(取代甲氧基)吡唑并[3,4-d]嘧啶衍生物的合成、表皮生长因子受体抑制作用及抗癌活性
Anticancer Agents Med Chem. 2017;17(10):1389-1400. doi: 10.2174/1872211311666170213105004.
7
Effects of newly synthetized isoquinoline derivatives on rat uterine contractility and ROCK II activity.新合成异喹啉衍生物对大鼠子宫收缩性及ROCK II活性的影响。
Bioorg Med Chem Lett. 2018 Feb 1;28(3):466-469. doi: 10.1016/j.bmcl.2017.12.017. Epub 2017 Dec 13.
8
Discovery of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-diones and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4.发现4-（苄基氨基亚甲基）异喹啉-1,3-（2H，4H）-二酮和4- [（吡啶基甲基）氨基亚甲基]异喹啉-1,3-（2H，4H）-二酮作为细胞周期蛋白依赖性激酶4的有效和选择性抑制剂。
J Med Chem. 2009 Apr 23;52(8):2289-310. doi: 10.1021/jm801026e.
9
Structural basis for selectivity of the isoquinoline sulfonamide family of protein kinase inhibitors.异喹啉磺酰胺类蛋白激酶抑制剂选择性的结构基础。
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6308-13. doi: 10.1073/pnas.93.13.6308.
10
Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines.取代的 2H-异喹啉-1-酮作为有效的 Rho-激酶抑制剂：第 3 部分，芳基取代的吡咯烷。
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3746-9. doi: 10.1016/j.bmcl.2010.04.069. Epub 2010 Apr 21.

本文引用的文献

1
Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity.Haspin抑制剂的合成与生物学评价：激酶抑制活性和细胞活性
Eur J Med Chem. 2022 Jun 5;236:114369. doi: 10.1016/j.ejmech.2022.114369. Epub 2022 Apr 9.
2
Recent Advances in Pain Management: Relevant Protein Kinases and Their Inhibitors.疼痛管理的最新进展：相关蛋白激酶及其抑制剂
Molecules. 2021 May 4;26(9):2696. doi: 10.3390/molecules26092696.
3
New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis.
新型吡啶并[3,4-g]喹唑啉衍生物作为 CLK1 和 DYRK1A 的抑制剂：合成、生物评价及结合模式分析。
Eur J Med Chem. 2019 Mar 15;166:304-317. doi: 10.1016/j.ejmech.2019.01.052. Epub 2019 Jan 26.
4
Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives.新型多样取代吡啶并[3,4 - g]喹唑啉衍生物的合成及初步体外激酶抑制活性评价
Bioorg Med Chem Lett. 2016 Sep 1;26(17):4327-9. doi: 10.1016/j.bmcl.2016.07.032. Epub 2016 Jul 16.
5
Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.发现吡啶并[3,4-g]喹唑啉衍生物作为 CMGC 家族蛋白激酶抑制剂：设计、合成、抑制活性和 X 射线共晶结构。
Eur J Med Chem. 2016 Aug 8;118:170-7. doi: 10.1016/j.ejmech.2016.04.004. Epub 2016 Apr 5.
6
Computational protein-ligand docking and virtual drug screening with the AutoDock suite.使用AutoDock套件进行蛋白质-配体对接计算和虚拟药物筛选。
Nat Protoc. 2016 May;11(5):905-19. doi: 10.1038/nprot.2016.051. Epub 2016 Apr 14.
7
Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.新型β-咔啉作为强效和选择性DYRK1激酶抑制剂的选择性分析及生物活性
PLoS One. 2015 Jul 20;10(7):e0132453. doi: 10.1371/journal.pone.0132453. eCollection 2015.
8
A force field with discrete displaceable waters and desolvation entropy for hydrated ligand docking.具有离散可移动水和去溶剂化熵的力场用于水合配体对接。
J Med Chem. 2012 Jan 26;55(2):623-38. doi: 10.1021/jm2005145. Epub 2012 Jan 13.
9
ADP-Glo: A Bioluminescent and homogeneous ADP monitoring assay for kinases.ADP-Glo：一种用于激酶的生物发光均相ADP监测检测方法。
Assay Drug Dev Technol. 2009 Dec;7(6):560-72. doi: 10.1089/adt.2009.0222.
10
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.AutoDock Vina：通过新的评分函数、高效优化和多线程改进对接的速度和准确性。
J Comput Chem. 2010 Jan 30;31(2):455-61. doi: 10.1002/jcc.21334.