• 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

碳酸酐酶抑制剂：4-取代-3-吡啶磺酰胺对人细胞质同工酶 I 和 II 以及跨膜同工酶 IX、XII（与癌症相关）和 XIV 的合成和抑制。

Carbonic anhydrase inhibitors: synthesis and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with 4-substituted 3-pyridinesulfonamides.

机构信息

Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.

出版信息

Eur J Med Chem. 2010 Jun;45(6):2396-404. doi: 10.1016/j.ejmech.2010.02.020. Epub 2010 Feb 12.

DOI:10.1016/j.ejmech.2010.02.020
PMID:20202722
Abstract

A series of novel 4-substituted-3-pyridinesulfonamides (2-27 and 31-33) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, the cytosolic, ubiquitous isozymes CA I and II, and transmembrane isozymes CA IX, XII (cancer-associated) and XIV. Against the human isozymes hCA I, the new compounds showed inhibition constants in the range of 0.078-11.7 microM, against hCA II in the range of 9.9-140 nM, against hCA IX in the range of 4.6-313 nM, against hCA XII in the range of 3.4-21.6 nM, and against hCA XIV in the range of 50.9-160 nM, respectively. Compounds 4, 6, 7, 9, 11-14, 19, 20, 22-24, 26, 27, 31 and 32 showed excellent hCA IX inhibitory efficacy, with inhibition constants of 4.6-12.0 nM, being much more effective as compared to the clinically used sulfonamides AAZ, MZA, EZA, DCP and IND. 4-[N'-(6-chloro-7-cyano-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazino]-3-pyridinesulfonamide (31) is the prominent of the compounds due to its remarkable inhibitory activity toward hCA I (KIs=0.078 microM), hCA IX (KIs=7.2 nM) and hCA XII (KIs=3.4 nM).

摘要

一系列新型 4-取代-3-吡啶磺酰胺（2-27 和 31-33）已被合成并作为五种锌酶碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制剂进行了研究，即细胞溶质、普遍存在的同工酶 CA I 和 II，以及跨膜同工酶 CA IX、XII（与癌症相关）和 XIV。针对人同工酶 hCA I，新化合物的抑制常数在 0.078-11.7 μM 范围内，对 hCA II 的抑制常数在 9.9-140 nM 范围内，对 hCA IX 的抑制常数在 4.6-313 nM 范围内，对 hCA XII 的抑制常数在 3.4-21.6 nM 范围内，对 hCA XIV 的抑制常数在 50.9-160 nM 范围内。化合物 4、6、7、9、11-14、19、20、22-24、26、27、31 和 32 对 hCA IX 具有优异的抑制作用，抑制常数为 4.6-12.0 nM，与临床使用的磺胺类药物 AAZ、MZA、EZA、DCP 和 IND 相比，效果要好得多。4-[N'-(6-氯-7-氰基-1,1-二氧代-1,4,2-苯并噻二嗪-3-基)腙基]-3-吡啶磺酰胺（31）是这些化合物中较为突出的一种，因为它对 hCA I（KIs=0.078 μM）、hCA IX（KIs=7.2 nM）和 hCA XII（KIs=3.4 nM）具有显著的抑制活性。

相似文献

1
Carbonic anhydrase inhibitors: synthesis and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with 4-substituted 3-pyridinesulfonamides.碳酸酐酶抑制剂：4-取代-3-吡啶磺酰胺对人细胞质同工酶 I 和 II 以及跨膜同工酶 IX、XII（与癌症相关）和 XIV 的合成和抑制。
Eur J Med Chem. 2010 Jun;45(6):2396-404. doi: 10.1016/j.ejmech.2010.02.020. Epub 2010 Feb 12.
2
Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII.碳酸酐酶抑制剂。新型 1-取代的 1,4-二氢-4-氧代-3-吡啶磺酰胺的区域选择性合成及其对人胞质同工酶 I 和 II 以及跨膜癌相关同工酶 IX 和 XII 的抑制作用。
Eur J Med Chem. 2010 Sep;45(9):3656-61. doi: 10.1016/j.ejmech.2010.05.011. Epub 2010 May 12.
3
Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series N-substituted N'-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII.碳酸酐酶抑制剂。新型 N-取代的 N'-(2-芳甲基硫代-4-氯-5-甲基苯磺酰)胍的合成及分子结构及其对人胞质同工酶 I 和 II 以及跨膜肿瘤相关同工酶 IX 和 XII 的抑制作用。
Eur J Med Chem. 2014 Jan;71:135-47. doi: 10.1016/j.ejmech.2013.10.081. Epub 2013 Nov 10.
4
Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives.碳酸酐酶抑制剂。新型 3-吡啶磺酰胺衍生物的合成、分子结构及对人胞质同工酶 I 和 II 以及跨膜同工酶 IX、XII（与癌症相关）和 XIV 的抑制作用。
Eur J Med Chem. 2011 Sep;46(9):4403-10. doi: 10.1016/j.ejmech.2011.07.011. Epub 2011 Jul 8.
5
Carbonic anhydrase inhibitors. Regioselective synthesis of novel series 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII.碳酸酐酶抑制剂。新型 1-取代 1,4-二氢-4-氧代-3-吡啶磺酰胺的区域选择性合成及其对人胞质同工酶 I 和 II 以及跨膜癌相关同工酶 IX 和 XII 的抑制作用。
Eur J Med Chem. 2012 Oct;56:282-91. doi: 10.1016/j.ejmech.2012.08.006. Epub 2012 Aug 11.
6
Synthesis of a new series of N⁴-substituted 4-(2-aminoethyl)benzenesulfonamides and their inhibitory effect on human carbonic anhydrase cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII.合成一系列新型的 N⁴-取代的 4-(2-氨乙基)苯磺酰胺及其对人碳酸酐酶胞质同工酶 I 和 II 以及跨膜肿瘤相关同工酶 IX 和 XII 的抑制作用。
Eur J Med Chem. 2014 Sep 12;84:59-67. doi: 10.1016/j.ejmech.2014.06.074. Epub 2014 Jul 5.
7
Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII.碳酸酐酶抑制剂。新型5-取代2,4-二氯苯磺酰胺系列的合成及其对人胞质同工酶I和II以及跨膜肿瘤相关同工酶IX和XII的抑制作用。
Eur J Med Chem. 2014 Jul 23;82:47-55. doi: 10.1016/j.ejmech.2014.05.039. Epub 2014 May 13.
8
Carbonic anhydrase inhibitors. Synthesis of heterocyclic 4-substituted pyridine-3-sulfonamide derivatives and their inhibition of the human cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII.碳酸酐酶抑制剂。杂环 4-取代吡啶-3-磺酰胺衍生物的合成及其对人胞质同工酶 I 和 II 以及跨膜肿瘤相关同工酶 IX 和 XII 的抑制作用。
Eur J Med Chem. 2013 Nov;69:701-10. doi: 10.1016/j.ejmech.2013.09.027. Epub 2013 Sep 20.
9
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, IX, and XII with N-hydroxysulfamides--a new zinc-binding function in the design of inhibitors.碳酸酐酶抑制剂：N-羟基磺胺类化合物对胞质/肿瘤相关碳酸酐酶同工酶I、II、IX和XII的合成及抑制作用——抑制剂设计中的一种新的锌结合功能
Bioorg Med Chem Lett. 2005 May 2;15(9):2353-8. doi: 10.1016/j.bmcl.2005.02.091.
10
Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.含磺酰胺基的吡唑基吡唑啉作为碳酸酐酶同工酶I、II、IX和XII的强效抑制剂。
Bioorg Med Chem Lett. 2015 Aug 15;25(16):3208-12. doi: 10.1016/j.bmcl.2015.05.096. Epub 2015 Jun 14.

引用本文的文献

1
Computational Discovery of Selective Carbonic Anhydrase IX (CA IX) Inhibitors via Pharmacophore Modeling and Molecular Simulations for Cancer Therapy.通过药效团建模和分子模拟进行选择性碳酸酐酶IX（CA IX）抑制剂的计算发现用于癌症治疗
Int J Mol Sci. 2025 Aug 30;26(17):8465. doi: 10.3390/ijms26178465.
2
4-Substituted Pyridine-3-Sulfonamides as Carbonic Anhydrase Inhibitors Modified by Click Tailing: Synthesis, Activity, and Docking Studies.通过点击尾化修饰的4-取代吡啶-3-磺酰胺类碳酸酐酶抑制剂：合成、活性及对接研究
Int J Mol Sci. 2025 Apr 17;26(8):3817. doi: 10.3390/ijms26083817.
3
Shared and Related Molecular Targets and Actions of Salicylic Acid in Plants and Humans.
水杨酸在植物和人类中的共享和相关分子靶标及作用。
Cells. 2023 Jan 4;12(2):219. doi: 10.3390/cells12020219.
4
New Sulfamethoxazole Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors: Design, Synthesis, Cytotoxic Activity and Molecular Modeling.新型磺胺甲恶唑衍生物作为选择性碳酸酐酶IX和XII抑制剂：设计、合成、细胞毒性活性及分子模拟
Pharmaceuticals (Basel). 2022 Sep 10;15(9):1134. doi: 10.3390/ph15091134.
5
Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors.新型 1,3,5-三嗪基氨基苯磺酰胺类化合物，包含氨醇、氨查耳酮和氨二苯乙烯结构基序，作为有效的抗万古霉素肠球菌（VRE）药物，同时也是碳酸酐酶 I、II、VII、IX 和 XII 的抑制剂。
Int J Mol Sci. 2021 Dec 26;23(1):231. doi: 10.3390/ijms23010231.
6
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors.新型三芳基咪唑-苯磺酰胺杂合体的设计、合成、生物评价及计算研究：作为有前途的碳酸酐酶 IX 和 XII 选择性抑制剂。
Molecules. 2021 Aug 4;26(16):4718. doi: 10.3390/molecules26164718.
7
Rational Design and Synthesis of Diverse Pyrimidine Molecules Bearing Sulfonamide Moiety as Novel ERK Inhibitors.合理设计和合成含磺酰胺部分的多种嘧啶分子作为新型 ERK 抑制剂。
Int J Mol Sci. 2019 Nov 8;20(22):5592. doi: 10.3390/ijms20225592.
8
Syntheses of Novel 4-Substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamide Derivatives with Potential Antifungal Activity.新型具有潜在抗真菌活性的 4-取代 N-(5-氨基-1H-1,2,4-三唑-3-基)吡啶-3-磺酰胺衍生物的合成。
Molecules. 2017 Nov 7;22(11):1926. doi: 10.3390/molecules22111926.
9
Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking.作为一类新型的刀豆脲酶抑制剂的磺酰胺连接的环丙沙星、磺胺嘧啶和金刚烷胺衍生物；合成、动力学机制及分子对接
Molecules. 2017 Aug 16;22(8):1352. doi: 10.3390/molecules22081352.
10
Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity.具有酪氨酸酶和脲酶抑制活性的手性吡唑并[4,3-e][1,2,4]三嗪磺酰胺的合成
J Enzyme Inhib Med Chem. 2017 Dec;32(1):99-105. doi: 10.1080/14756366.2016.1238362. Epub 2016 Oct 25.