• 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

哒嗪酮衍生物作为潜在的抗炎剂：作为磷酸二酯酶4（PDE4）抑制剂的合成与生物学评价

Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors.

作者信息

Allart-Simon Ingrid, Moniot Aurélie, Bisi Nicolo, Ponce-Vargas Miguel, Audonnet Sandra, Laronze-Cochard Marie, Sapi Janos, Hénon Eric, Velard Frédéric, Gérard Stéphane

机构信息

Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), UMR CNRS 7312, UFR Sciences, Moulin de la housse and UFR Pharmacie 51 rue Cognacq-Jay F-51096 Reims France

Université de Reims-Champagne-Ardenne, EA 4691 Biomatériaux & Inflammation en site OSseux (BIOS), UFR Pharmacie and UFR Odontologie 51 rue Cognacq-Jay F-51096 Reims France.

出版信息

RSC Med Chem. 2021 Mar 1;12(4):584-592. doi: 10.1039/d0md00423e. eCollection 2021 Apr 28.

DOI:10.1039/d0md00423e
PMID:34046629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8127987/
Abstract

Cyclic nucleotide phosphodiesterase type 4 (PDE4), which controls the intracellular level of cyclic adenosine monophosphate (cAMP), has aroused scientific attention as a suitable target for anti-inflammatory therapy of respiratory diseases. This work describes the development and characterization of pyridazinone derivatives bearing an indole moiety as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4-(5-methoxy-1-indol-3-yl)-6-methylpyridazin-3(2)-one possesses promising activity, and selectivity towards PDE4B isoenzymes and is able to regulate potent pro-inflammatory cytokine and chemokine production by human primary macrophages.

摘要

4型环核苷酸磷酸二酯酶（PDE4）可控制细胞内环磷酸腺苷（cAMP）的水平，作为呼吸系统疾病抗炎治疗的合适靶点已引起科学界的关注。本文描述了带有吲哚部分的哒嗪酮衍生物作为潜在PDE4抑制剂的开发与特性，并将其作为抗炎剂进行了评估。在这些衍生物中，4-(5-甲氧基-1-吲哚-3-基)-6-甲基哒嗪-3(2)-酮具有良好的活性，对PDE4B同工酶具有选择性，并且能够调节人原代巨噬细胞中强效促炎细胞因子和趋化因子的产生。

相似文献

1
Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors.哒嗪酮衍生物作为潜在的抗炎剂：作为磷酸二酯酶4（PDE4）抑制剂的合成与生物学评价
RSC Med Chem. 2021 Mar 1;12(4):584-592. doi: 10.1039/d0md00423e. eCollection 2021 Apr 28.
2
Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents.哒嗪酮衍生物的合成及作为潜在抗炎剂的生物评价。
Eur J Med Chem. 2018 Feb 25;146:139-146. doi: 10.1016/j.ejmech.2018.01.035. Epub 2018 Jan 17.
3
Synthesis, Docking and Anti-Inflammatory Activity of Triazole Amine Derivatives as Potential Phosphodiesterase-4 Inhibitors.作为潜在磷酸二酯酶-4抑制剂的三唑胺衍生物的合成、对接及抗炎活性
Antiinflamm Antiallergy Agents Med Chem. 2017;16(1):58-67. doi: 10.2174/1871523016666170616115752.
4
Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships.联苯哒嗪酮衍生物作为吸入性磷酸二酯酶4抑制剂：结构生物学与构效关系
J Med Chem. 2016 Dec 8;59(23):10479-10497. doi: 10.1021/acs.jmedchem.6b00829. Epub 2016 Nov 17.
5
Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3-Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7.一些新型1,3-噻唑烷-2,4-二酮衍生物作为磷酸二酯酶4和磷酸二酯酶7双重抑制剂的合成、抗炎活性及对接研究
Curr Comput Aided Drug Des. 2019;15(3):225-234. doi: 10.2174/1573409914666181003151528.
6
Design, synthesis and biological evaluation of novel tetrahydroisoquinoline derivatives as potential PDE4 inhibitors.新型四氢异喹啉衍生物作为潜在PDE4抑制剂的设计、合成及生物学评价
Bioorg Med Chem Lett. 2015 Oct 15;25(20):4610-4. doi: 10.1016/j.bmcl.2015.08.043. Epub 2015 Aug 21.
7
Phosphodiesterase inhibitors in airways disease.气道疾病中的磷酸二酯酶抑制剂
Eur J Pharmacol. 2006 Mar 8;533(1-3):110-7. doi: 10.1016/j.ejphar.2005.12.059. Epub 2006 Feb 2.
8
Phosphodiesterase 4 and its inhibitors in inflammatory diseases.磷酸二酯酶4及其抑制剂在炎症性疾病中的作用
Chang Gung Med J. 2012 May-Jun;35(3):197-210. doi: 10.4103/2319-4170.106152.
9
Selective up-regulation of phosphodiesterase-4 cyclic adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase variants by elevated cAMP content in human myometrial cells in culture.培养的人子宫肌层细胞中，环磷酸腺苷（cAMP）含量升高导致磷酸二酯酶4环腺苷3',5'-单磷酸（cAMP）特异性磷酸二酯酶变体的选择性上调。
Endocrinology. 1999 Jul;140(7):3228-37. doi: 10.1210/endo.140.7.6847.
10
CuCl-catalyzed inexpensive, faster and ligand/additive free synthesis of isoquinolin-1(2H)-one derivatives via the coupling-cyclization strategy: Evaluation of a new class of compounds as potential PDE4 inhibitors.CuCl 催化的廉价、快速、无需配体/添加剂的异喹啉-1(2H)-酮衍生物的偶联-环化策略合成：作为潜在 PDE4 抑制剂的新型化合物的评估。
Bioorg Chem. 2021 Oct;115:105265. doi: 10.1016/j.bioorg.2021.105265. Epub 2021 Aug 13.

引用本文的文献

1
Diverse Pharmacological Potential of Pyridazine Analogs against Various Diseases.哒嗪类似物对多种疾病的多样化药理潜力。
Med Chem. 2024;20(3):245-267. doi: 10.2174/1573406419666230913102835.
2
PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes.PDE4 抑制剂：通过多种结构类别对命中化合物进行剖析。
Int J Mol Sci. 2023 Jul 15;24(14):11518. doi: 10.3390/ijms241411518.
3
The regulatory role of PDE4B in the progression of inflammatory function study.磷酸二酯酶4B（PDE4B）在炎症功能进展中的调节作用研究
Front Pharmacol. 2022 Oct 6;13:982130. doi: 10.3389/fphar.2022.982130. eCollection 2022.
4
Inhibition of Recruitment and Activation of Neutrophils by Pyridazinone-Scaffold-Based Compounds.基于哒嗪酮骨架的化合物对中性粒细胞募集和激活的抑制作用。
Int J Mol Sci. 2022 Jun 29;23(13):7226. doi: 10.3390/ijms23137226.
5
Pyridazinones and Structurally Related Derivatives with Anti-Inflammatory Activity.具有抗炎活性的哒嗪酮和结构相关衍生物。
Molecules. 2022 Jun 10;27(12):3749. doi: 10.3390/molecules27123749.
6
Autoxidation of 4-Hydrazinylquinolin-2(1)-one; Synthesis of Pyridazino[4,3-:5,6-']diquinoline-6,7(5,8)-diones.4-肼基喹啉-2(1H)-酮的自动氧化；哒嗪并[4,3-:5,6-']二喹啉-6,7(5,8)-二酮的合成。
Molecules. 2022 Mar 25;27(7):2125. doi: 10.3390/molecules27072125.
7
Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo.哒嗪酮衍生物在体外和体内均能抑制骨肉瘤细胞的生长。
Cancers (Basel). 2021 Nov 28;13(23):5992. doi: 10.3390/cancers13235992.

本文引用的文献

1
Advances in the Development of Phosphodiesterase-4 Inhibitors.磷酸二酯酶-4 抑制剂的研究进展。
J Med Chem. 2020 Oct 8;63(19):10594-10617. doi: 10.1021/acs.jmedchem.9b02170. Epub 2020 Jun 10.
2
Lung Macrophage Functional Properties in Chronic Obstructive Pulmonary Disease.慢性阻塞性肺疾病中的肺巨噬细胞功能特性。
Int J Mol Sci. 2020 Jan 28;21(3):853. doi: 10.3390/ijms21030853.
3
Asthma control and COPD symptom burden in patients using fixed-dose combination inhalers (SPRINT study).固定剂量复方吸入器治疗患者的哮喘控制和 COPD 症状负担（SPRINT 研究）。
NPJ Prim Care Respir Med. 2020 Jan 7;30(1):1. doi: 10.1038/s41533-019-0159-1.
4
Atomic Decomposition Scheme of Noncovalent Interactions Applied to Host-Guest Assemblies.非共价相互作用的原子分解方案在主客体组装中的应用。
J Chem Inf Model. 2020 Jan 27;60(1):268-278. doi: 10.1021/acs.jcim.9b01016. Epub 2020 Jan 13.
5
Long-term macrolide treatment for the prevention of acute exacerbations in COPD: a systematic review and meta-analysis.长期使用大环内酯类药物预防慢性阻塞性肺疾病急性加重：一项系统评价和荟萃分析。
Int J Chron Obstruct Pulmon Dis. 2018 Nov 22;13:3813-3829. doi: 10.2147/COPD.S181246. eCollection 2018.
6
Inhibitors of phosphodiesterase as cancer therapeutics.磷酸二酯酶抑制剂作为癌症治疗药物
Eur J Med Chem. 2018 Apr 25;150:742-756. doi: 10.1016/j.ejmech.2018.03.046. Epub 2018 Mar 16.
7
Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents.哒嗪酮衍生物的合成及作为潜在抗炎剂的生物评价。
Eur J Med Chem. 2018 Feb 25;146:139-146. doi: 10.1016/j.ejmech.2018.01.035. Epub 2018 Jan 17.
8
Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density.准确提取约化密度梯度与电子密度的NCI图中存在的分子间相互作用的特征。
Phys Chem Chem Phys. 2017 Jul 21;19(27):17928-17936. doi: 10.1039/c7cp02110k. Epub 2017 Jun 30.
9
Human lung and monocyte-derived macrophages differ with regard to the effects of β-adrenoceptor agonists on cytokine release.人肺巨噬细胞和单核细胞衍生的巨噬细胞在β-肾上腺素能受体激动剂对细胞因子释放的影响方面存在差异。
Respir Res. 2017 Jun 21;18(1):126. doi: 10.1186/s12931-017-0613-y.
10
Ovarian hormones in innate inflammation.先天炎症中的卵巢激素。
Immunobiology. 2017 Aug;222(8-9):878-883. doi: 10.1016/j.imbio.2017.05.007. Epub 2017 May 20.