• 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

脂肪酸酰胺水解酶（FAAH）的苯并噻吩哌嗪和哌啶脲抑制剂。

Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH).

作者信息

Johnson Douglas S, Ahn Kay, Kesten Suzanne, Lazerwith Scott E, Song Yuntao, Morris Mark, Fay Lorraine, Gregory Tracy, Stiff Cory, Dunbar James B, Liimatta Marya, Beidler David, Smith Sarah, Nomanbhoy Tyzoon K, Cravatt Benjamin F

机构信息

Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.

出版信息

Bioorg Med Chem Lett. 2009 May 15;19(10):2865-9. doi: 10.1016/j.bmcl.2009.03.080. Epub 2009 Mar 24.

DOI:10.1016/j.bmcl.2009.03.080
PMID:19386497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3150822/
Abstract

The synthesis and structure-activity relationships (SAR) of a series of benzothiophene piperazine and piperidine urea FAAH inhibitors is described. These compounds inhibit FAAH by covalently modifying the enzyme's active site serine nucleophile. Activity-based protein profiling (ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Several compounds showed in vivo activity in a rat complete Freund's adjuvant (CFA) model of inflammatory pain.

摘要

描述了一系列苯并噻吩哌嗪和哌啶脲脂肪酸酰胺水解酶（FAAH）抑制剂的合成及其构效关系（SAR）。这些化合物通过共价修饰酶的活性位点丝氨酸亲核试剂来抑制FAAH。基于活性的蛋白质谱分析（ABPP）表明，相对于其他哺乳动物丝氨酸水解酶，这些脲抑制剂对FAAH具有完全选择性。几种化合物在大鼠完全弗氏佐剂（CFA）炎性疼痛模型中显示出体内活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/1cbdc70ad33e/nihms298813f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/97555aa5b2a5/nihms298813f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/36d4af8943be/nihms298813f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/28e30853d11c/nihms298813f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/b0ac33061893/nihms298813f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/c071cf5d5ce3/nihms298813f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/e0f47e0686f7/nihms298813f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/60b53d7cdf11/nihms298813f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/4c6950b22a97/nihms298813f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/8b110807bd2b/nihms298813f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/1cbdc70ad33e/nihms298813f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/97555aa5b2a5/nihms298813f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/36d4af8943be/nihms298813f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/28e30853d11c/nihms298813f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/b0ac33061893/nihms298813f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/c071cf5d5ce3/nihms298813f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/e0f47e0686f7/nihms298813f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/60b53d7cdf11/nihms298813f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/4c6950b22a97/nihms298813f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/8b110807bd2b/nihms298813f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf1/3150822/1cbdc70ad33e/nihms298813f10.jpg

相似文献

1
Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH).脂肪酸酰胺水解酶（FAAH）的苯并噻吩哌嗪和哌啶脲抑制剂。
Bioorg Med Chem Lett. 2009 May 15;19(10):2865-9. doi: 10.1016/j.bmcl.2009.03.080. Epub 2009 Mar 24.
2
Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity.具有显著选择性的新型脂肪酸酰胺水解酶抑制剂的作用机制类别
Biochemistry. 2007 Nov 13;46(45):13019-30. doi: 10.1021/bi701378g. Epub 2007 Oct 19.
3
Piperazine and piperidine carboxamides and carbamates as inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).哌嗪和哌啶甲酰胺及氨基甲酸酯类作为脂肪酸酰胺水解酶（FAAH）和单酰甘油脂肪酶（MAGL）的抑制剂。
Bioorg Med Chem. 2014 Dec 1;22(23):6694-6705. doi: 10.1016/j.bmc.2014.09.012. Epub 2014 Sep 16.
4
Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain.一种可减轻炎性疼痛的高选择性脂肪酸酰胺水解酶（FAAH）抑制剂的发现与特性研究
Chem Biol. 2009 Apr 24;16(4):411-20. doi: 10.1016/j.chembiol.2009.02.013.
5
Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain.PF-04457845 的作用机制和药理学特性研究：一种高效且选择性的脂肪酸酰胺水解酶抑制剂，可减轻炎症性和非炎症性疼痛。
J Pharmacol Exp Ther. 2011 Jul;338(1):114-24. doi: 10.1124/jpet.111.180257. Epub 2011 Apr 19.
6
Characterization of tunable piperidine and piperazine carbamates as inhibitors of endocannabinoid hydrolases.哌啶和哌嗪氨基甲酸酯作为内源性大麻素水解酶抑制剂的构效关系研究。
J Med Chem. 2010 Feb 25;53(4):1830-42. doi: 10.1021/jm9016976.
7
Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology.脂肪酸酰胺水解酶抑制剂哌啶和哌嗪针对兴奋毒性病理学。
Bioorg Med Chem. 2019 Dec 1;27(23):115096. doi: 10.1016/j.bmc.2019.115096. Epub 2019 Sep 10.
8
Covalent inhibitors of fatty acid amide hydrolase: a rationale for the activity of piperidine and piperazine aryl ureas.脂肪酸酰胺水解酶的共价抑制剂：哌啶和哌嗪芳基脲活性的原理。
J Med Chem. 2011 Oct 13;54(19):6612-23. doi: 10.1021/jm2004283. Epub 2011 Sep 8.
9
Heteroarylureas with fused bicyclic diamine cores as inhibitors of fatty acid amide hydrolase.具有稠合双环二胺核的杂芳基脲作为脂肪酸酰胺水解酶抑制剂。
Bioorg Med Chem Lett. 2020 Oct 15;30(20):127463. doi: 10.1016/j.bmcl.2020.127463. Epub 2020 Aug 9.
10
Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.从生物活性分子中挖掘脂肪酸酰胺水解酶（FAAH）抑制剂：苯丁锡和安比西林被鉴定为 FAAH 抑制剂。
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6793-6. doi: 10.1016/j.bmcl.2009.09.086. Epub 2009 Sep 30.

引用本文的文献

1
The pyridazine heterocycle in molecular recognition and drug discovery.哒嗪杂环在分子识别与药物发现中的应用
Med Chem Res. 2023 Mar 15:1-69. doi: 10.1007/s00044-023-03035-9.
2
Synthesis and Evaluation of 3-Halobenzo[]thiophenes as Potential Antibacterial and Antifungal Agents.3-卤代苯并噻吩作为潜在抗菌和抗真菌剂的合成与评价
Pharmaceuticals (Basel). 2021 Dec 28;15(1):39. doi: 10.3390/ph15010039.
3
Copper-Catalyzed Electrophilic Chlorocyclization Reaction Using Sodium Chloride as the Source of Electrophilic Chlorine.以氯化钠作为亲电氯源的铜催化亲电氯环化反应

本文引用的文献

1
Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase.4-（3-苯基-[1,2,4]噻二唑-5-基）-哌嗪-1-羧酸苯酰胺的生化及生物学特性，一种基于机制的脂肪酸酰胺水解酶抑制剂
Anesth Analg. 2009 Jan;108(1):316-29. doi: 10.1213/ane.0b013e31818c7cbd.
2
Discovery and development of fatty acid amide hydrolase (FAAH) inhibitors.脂肪酸酰胺水解酶（FAAH）抑制剂的发现与开发。
J Med Chem. 2008 Dec 11;51(23):7327-43. doi: 10.1021/jm800311k.
3
Structure-guided inhibitor design for human FAAH by interspecies active site conversion.
ACS Omega. 2019 Apr 9;4(4):6538-6545. doi: 10.1021/acsomega.9b00300. eCollection 2019 Apr 30.
4
Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells.通过抑制或敲低 BV2 小胶质细胞中的脂肪酸酰胺水解酶发挥抗炎作用。
Cells. 2019 May 22;8(5):491. doi: 10.3390/cells8050491.
5
Discovery of a Potent, Long-Acting, and CNS-Active Inhibitor (BIA 10-2474) of Fatty Acid Amide Hydrolase.发现一种强效、长效且中枢神经系统活性的脂肪酸酰胺水解酶抑制剂（BIA 10-2474）。
ChemMedChem. 2018 Oct 22;13(20):2177-2188. doi: 10.1002/cmdc.201800393. Epub 2018 Sep 11.
6
Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.对脂肪酸酰胺水解酶具有双重活性的可溶性环氧化物水解酶抑制剂的鉴定与优化。
Bioorg Med Chem Lett. 2018 Feb 15;28(4):762-768. doi: 10.1016/j.bmcl.2018.01.003. Epub 2018 Jan 4.
7
Piperidinyl thiazole isoxazolines: A new series of highly potent, slowly reversible FAAH inhibitors with analgesic properties.哌啶基噻唑异恶唑啉类：一类具有镇痛特性的新型高效、缓慢可逆的脂肪酸酰胺水解酶抑制剂。
Bioorg Med Chem Lett. 2016 Jun 15;26(12):2965-2973. doi: 10.1016/j.bmcl.2016.02.061. Epub 2016 Feb 22.
8
Preclinical Characterization of the FAAH Inhibitor JNJ-42165279.脂肪酸酰胺水解酶（FAAH）抑制剂JNJ-42165279的临床前特性研究
ACS Med Chem Lett. 2015 Nov 2;6(12):1204-8. doi: 10.1021/acsmedchemlett.5b00353. eCollection 2015 Dec 10.
9
Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and esters.苄基醚和酯的立体选择性镍催化交叉偶联反应。
Acc Chem Res. 2015 Aug 18;48(8):2344-53. doi: 10.1021/acs.accounts.5b00223. Epub 2015 Jul 21.
10
O-(triazolyl)methyl carbamates as a novel and potent class of fatty acid amide hydrolase (FAAH) inhibitors.O-（三唑基）甲基氨基甲酸酯类作为一类新型强效脂肪酸酰胺水解酶（FAAH）抑制剂。
ChemMedChem. 2015 Feb;10(2):380-95. doi: 10.1002/cmdc.201402374. Epub 2014 Oct 22.
通过种间活性位点转换进行人脂肪酸酰胺水解酶的结构导向抑制剂设计。
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12820-4. doi: 10.1073/pnas.0806121105. Epub 2008 Aug 27.
4
Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase.噻二唑并哌嗪基脲类化合物作为脂肪酸酰胺水解酶抑制剂
Bioorg Med Chem Lett. 2008 Sep 1;18(17):4838-43. doi: 10.1016/j.bmcl.2008.07.081. Epub 2008 Jul 25.
5
Optimization of the central heterocycle of alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase.脂肪酸酰胺水解酶的α-酮杂环抑制剂中心杂环的优化
J Med Chem. 2008 Aug 14;51(15):4392-403. doi: 10.1021/jm800136b. Epub 2008 Jul 16.
6
Targeting the endocannabinoid system: to enhance or reduce?靶向内源性大麻素系统：增强还是降低？
Nat Rev Drug Discov. 2008 May;7(5):438-55. doi: 10.1038/nrd2553.
7
Enzymatic pathways that regulate endocannabinoid signaling in the nervous system.调节神经系统内源性大麻素信号传导的酶促途径。
Chem Rev. 2008 May;108(5):1687-707. doi: 10.1021/cr0782067. Epub 2008 Apr 23.
8
Activity-based protein profiling: from enzyme chemistry to proteomic chemistry.基于活性的蛋白质谱分析：从酶化学到蛋白质组化学
Annu Rev Biochem. 2008;77:383-414. doi: 10.1146/annurev.biochem.75.101304.124125.
9
Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity.具有显著选择性的新型脂肪酸酰胺水解酶抑制剂的作用机制类别
Biochemistry. 2007 Nov 13;46(45):13019-30. doi: 10.1021/bi701378g. Epub 2007 Oct 19.
10
Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets.脂肪酸酰胺水解酶抑制剂具有广泛的选择性，并会抑制多种羧酸酯酶作为脱靶效应。
Neuropharmacology. 2007 Mar;52(4):1095-105. doi: 10.1016/j.neuropharm.2006.11.009. Epub 2007 Jan 9.