• 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

探索 7-氧代噻唑并[5,4-d]嘧啶核心，设计新型人腺嘌呤 A3 受体拮抗剂。合成、分子模拟研究和药理学评价。

Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation.

机构信息

Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Universita' di Firenze, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.

Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Universita' di Firenze, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.

出版信息

Eur J Med Chem. 2015;96:105-21. doi: 10.1016/j.ejmech.2015.04.010. Epub 2015 Apr 4.

DOI:10.1016/j.ejmech.2015.04.010
PMID:25874336
Abstract

A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A1, A2A, and A3 adenosine receptors (ARs). Efficacy at the hA(2B) and antagonism of selected ligands at the hA3 were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA3AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (K(I) hA3 = 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA3 receptor model.

摘要

合成了一系列在 2 位具有不同取代基（芳基、杂芳基和芳氨基）的 5-甲基-噻唑并[5,4-d]嘧啶-7-酮，并在放射性配体结合测定中对其进行了评估，以确定它们与人（h）A1、A2A 和 A3 腺苷受体（AR）的亲和力。还通过 cAMP 实验评估了 hA(2B)的效能和选定配体对 hA3 的拮抗作用。一些新的衍生物表现出对 hA3AR 的良好至高亲和力和选择性，与所有其他 AR 亚型相比。发现化合物 2-(4-氯苯基)-5-甲基-噻唑并[5,4-d]嘧啶-7-酮 4 是该系列中最有效和选择性的配体（K(I)hA3 = 18 nM）。对报道的衍生物进行了分子对接研究，以描绘它们在我们的 hA3 受体模型中的假设结合模式。

相似文献

1
Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation.探索 7-氧代噻唑并[5,4-d]嘧啶核心，设计新型人腺嘌呤 A3 受体拮抗剂。合成、分子模拟研究和药理学评价。
Eur J Med Chem. 2015;96:105-21. doi: 10.1016/j.ejmech.2015.04.010. Epub 2015 Apr 4.
2
Structural refinement of pyrazolo[4,3-d]pyrimidine derivatives to obtain highly potent and selective antagonists for the human A3 adenosine receptor.吡唑并[4,3-d]嘧啶衍生物的结构优化，以获得对人A3腺苷受体具有高效能和高选择性的拮抗剂。
Eur J Med Chem. 2016 Jan 27;108:117-133. doi: 10.1016/j.ejmech.2015.11.015. Epub 2015 Nov 17.
3
A facile and novel synthesis of N(2)-, C(6)-substituted pyrazolo[3,4-d]pyrimidine-4 carboxylate derivatives as adenosine receptor antagonists.一种简便新颖的 N(2)-、C(6)-取代的吡唑并[3,4-d]嘧啶-4 羧酸酯衍生物的合成方法，作为腺苷受体拮抗剂。
Eur J Med Chem. 2015 Mar 6;92:784-98. doi: 10.1016/j.ejmech.2015.01.046. Epub 2015 Jan 22.
4
2-Arylpyrazolo[4,3-d]pyrimidin-7-amino derivatives as new potent and selective human A3 adenosine receptor antagonists. Molecular modeling studies and pharmacological evaluation.2-芳基吡唑并[4,3-d]嘧啶-7-氨基衍生物作为新型强效和选择性人 A3 腺苷受体拮抗剂。分子模拟研究和药理学评价。
J Med Chem. 2013 Mar 28;56(6):2256-69. doi: 10.1021/jm400068e. Epub 2013 Mar 7.
5
New 2-heterocyclyl-imidazo[2,1-i]purin-5-one derivatives as potent and selective human A3 adenosine receptor antagonists.新型 2-杂环基-咪唑并[2,1-i]嘌呤-5-酮衍生物作为有效的和选择性的人 A3 腺苷受体拮抗剂。
J Med Chem. 2011 Jul 28;54(14):5205-20. doi: 10.1021/jm2004738. Epub 2011 Jun 28.
6
Novel human adenosine receptor antagonists based on the 7-amino-thiazolo[5,4-d]pyrimidine scaffold. Structural investigations at the 2-, 5- and 7-positions to enhance affinity and tune selectivity.基于 7-氨基噻唑并[5,4-d]嘧啶骨架的新型人腺苷受体拮抗剂。在 2-、5-和 7-位进行结构研究，以提高亲和力和调节选择性。
Bioorg Med Chem Lett. 2019 Feb 15;29(4):563-569. doi: 10.1016/j.bmcl.2018.12.062. Epub 2018 Dec 31.
7
1,2,4-triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A₃ receptor antagonists. Synthesis, structure-affinity relationships and molecular modeling studies.1,2,4-三唑并[1,5-a]喹喔啉衍生物及其简化类似物作为腺苷A₃受体拮抗剂。合成、构效关系及分子模拟研究。
Bioorg Med Chem. 2015 Jan 1;23(1):9-21. doi: 10.1016/j.bmc.2014.11.033. Epub 2014 Nov 27.
8
Imidazo[1,2-a]pyrazin-8-amine core for the design of new adenosine receptor antagonists: Structural exploration to target the A and A subtypes.咪唑并[1,2-a]吡嗪-8-胺核心用于设计新型腺苷受体拮抗剂：针对 A 和 A2a 亚型的结构探索。
Eur J Med Chem. 2017 Jan 5;125:611-628. doi: 10.1016/j.ejmech.2016.09.076. Epub 2016 Sep 26.
9
Synthesis of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: potent and selective adenosine A3 receptor antagonists.新型吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶衍生物的合成：有效的和选择性的腺苷 A3 受体拮抗剂。
Arch Pharm (Weinheim). 2013 Oct;346(10):699-707. doi: 10.1002/ardp.201300003. Epub 2013 Aug 30.
10
Pyrimidine derivatives as potent and selective A3 adenosine receptor antagonists.嘧啶衍生物作为强效和选择性的 A3 腺苷受体拮抗剂。
J Med Chem. 2011 Jan 27;54(2):457-71. doi: 10.1021/jm100843z. Epub 2010 Dec 27.

引用本文的文献

1
Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives with High Affinity for Both the Adenosine A and A Receptors, and Efficacy in Animal Models of Depression.对腺苷A1和A2A受体具有高亲和力且在抑郁症动物模型中有效的新型噻唑并[5,4-d]嘧啶衍生物的设计与合成
Pharmaceuticals (Basel). 2021 Jul 9;14(7):657. doi: 10.3390/ph14070657.
2
Exploring novel capping framework: high substituent pyridine-hydroxamic acid derivatives as potential antiproliferative agents.探索新型盖帽框架：高取代吡啶-羟肟酸衍生物作为潜在的抗增殖剂。
Daru. 2021 Dec;29(2):291-310. doi: 10.1007/s40199-021-00406-8. Epub 2021 Jul 23.
3
Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.
探讨查耳酮类和相关杂环化合物作为腺苷受体配体的应用：治疗学开发。
Mol Divers. 2022 Jun;26(3):1779-1821. doi: 10.1007/s11030-021-10257-9. Epub 2021 Jun 27.
4
Design, synthesis, and biological evaluation of new thiazolo[5,4-]pyrimidine derivatives as potent antiproliferative agents.新型噻唑并[5,4 -]嘧啶衍生物作为强效抗增殖剂的设计、合成及生物学评价
Medchemcomm. 2017 Jun 22;8(8):1655-1658. doi: 10.1039/c7md00165g. eCollection 2017 Aug 1.
5
The role of 5-arylalkylamino- and 5-piperazino- moieties on the 7-aminopyrazolo[4,3-d]pyrimidine core in affecting adenosine A and A receptor affinity and selectivity profiles.7-氨基吡唑并[4,3-d]嘧啶核心上的5-芳基烷基氨基和5-哌嗪基部分对腺苷A和A受体亲和力及选择性谱的影响。
J Enzyme Inhib Med Chem. 2017 Dec;32(1):248-263. doi: 10.1080/14756366.2016.1247060.