α-取代的2-(3-氟-4-甲基磺酰胺基苯基)乙酰胺作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂。
α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.
作者信息
Tran Phuong-Thao, Kim Ho Shin, Ann Jihyae, Kim Sung-Eun, Kim Changhoon, Hong Mannkyu, Hoang Van-Hai, Ngo Van T H, Hong Sunhye, Cui Minghua, Choi Sun, Blumberg Peter M, Frank-Foltyn Robert, Bahrenberg Gregor, Stockhausen Hannelore, Christoph Thomas, Lee Jeewoo
机构信息
Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
National Leading Research Laboratory of Molecular Modeling & Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
出版信息
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2326-30. doi: 10.1016/j.bmcl.2015.04.024. Epub 2015 Apr 12.
Abstract
A series of α-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an α-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with Ki(CAP)=0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor.
摘要
对先前报道的2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺类先导化合物(1,2)的一系列α-取代乙酰胺衍生物进行了研究，以考察其对辣椒素激活人瞬时受体电位香草酸亚型1(hTRPV1)的拮抗作用。具有α-间甲苯基取代基的化合物34对辣椒素表现出高效且选择性的拮抗作用，其Ki(CAP)=0.1 nM。因此，其效力比母体化合物1提高了3倍。使用我们的同源模型进行的对接分析表明，化合物34的高效力可能归因于间甲苯基与受体之间特定的疏水相互作用。
相似文献
1
α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.α-取代的2-(3-氟-4-甲基磺酰胺基苯基)乙酰胺作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂。
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2326-30. doi: 10.1016/j.bmcl.2015.04.024. Epub 2015 Apr 12.
2
2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists.2-(卤代苯基)乙酰胺和丙酰胺类作为有效的 TRPV1 拮抗剂。
Bioorg Med Chem Lett. 2021 Sep 15;48:128266. doi: 10.1016/j.bmcl.2021.128266. Epub 2021 Jul 14.
3
4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.4-氨基苯乙酰胺和丙酰胺类化合物作为潜在的瞬时受体电位香草酸 1 型（TRPV1）配体。
Bioorg Med Chem. 2018 Aug 15;26(15):4509-4517. doi: 10.1016/j.bmc.2018.07.040. Epub 2018 Jul 25.
4
Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin.对 4-羟基/氨基-3-甲氧基苯乙酰胺 TRPV1 激动剂进行卤化处理显示出对辣椒素的增强拮抗作用。
Bioorg Med Chem. 2010 Nov 15;18(22):8092-105. doi: 10.1016/j.bmc.2010.09.001. Epub 2010 Sep 18.
5
2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺作为有效的瞬时受体电位香草酸 1（TRPV1）拮抗剂：N-(6-三氟甲基吡啶-3-基甲基)C 区 2-氨基衍生物的结构活性关系。
J Med Chem. 2012 Oct 11;55(19):8392-408. doi: 10.1021/jm300780p. Epub 2012 Sep 20.
6
Structure activity relationships of benzyl C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺的苄基C区域类似物作为有效的TRPV1拮抗剂的构效关系
Bioorg Med Chem. 2015 Nov 1;23(21):6844-54. doi: 10.1016/j.bmc.2015.10.001. Epub 2015 Oct 9.
7
t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的叔丁基吡啶和苯基C区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2017 Apr 15;25(8):2451-2462. doi: 10.1016/j.bmc.2017.03.004. Epub 2017 Mar 6.
8
2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺的2-磺酰胺基吡啶C区类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2016 Mar 15;24(6):1231-40. doi: 10.1016/j.bmc.2016.01.051. Epub 2016 Jan 28.
9
Discovery of indane propanamides as potent and selective TRPV1 antagonists.茚满丙酰胺作为强效和选择性TRPV1拮抗剂的发现。
Bioorg Med Chem Lett. 2020 Feb 1;30(3):126838. doi: 10.1016/j.bmcl.2019.126838. Epub 2019 Dec 3.
10
Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的吡唑C区类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4383-4388. doi: 10.1016/j.bmcl.2017.08.020. Epub 2017 Aug 12.
引用本文的文献
1
Prediction of Lipophilicity and Pharmacokinetics of Chloroacetamides by Chemometric Approach.化学计量学方法预测氯乙酰胺的亲脂性和药代动力学
Iran J Pharm Res. 2018 Winter;17(1):100-114.
2
Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的吡唑C区类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4383-4388. doi: 10.1016/j.bmcl.2017.08.020. Epub 2017 Aug 12.
3
t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的叔丁基吡啶和苯基C区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2017 Apr 15;25(8):2451-2462. doi: 10.1016/j.bmc.2017.03.004. Epub 2017 Mar 6.
4
Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template.发现N-（3-氟-4-甲基磺酰胺基甲基苯基）脲作为一种有效的TRPV1拮抗剂模板。
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3603-7. doi: 10.1016/j.bmcl.2016.06.010. Epub 2016 Jun 7.
本文引用的文献
1
2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的2-芳基取代吡啶C区域类似物作为高效TRPV1拮抗剂。
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4044-7. doi: 10.1016/j.bmcl.2014.05.072. Epub 2014 Jun 2.
2
2-Alkyl/alkenyl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的2-烷基/烯基取代吡啶C区类似物作为高效TRPV1拮抗剂。
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4039-43. doi: 10.1016/j.bmcl.2014.05.074. Epub 2014 Jun 2.
3
Modulation of the TRPV1 channel: current clinical trials and recent patents with focus on neurological conditions.瞬时受体电位香草酸亚型1（TRPV1）通道的调控：当前临床试验及聚焦于神经系统疾病的近期专利
Recent Pat CNS Drug Discov. 2013 Dec;8(3):180-204. doi: 10.2174/1574889808666131209124012.
4
TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides.具有高镇痛疗效的 TRPV1 拮抗剂：2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的 2-噻吩基 C-区类似物。
Bioorg Med Chem. 2013 Nov 1;21(21):6657-64. doi: 10.1016/j.bmc.2013.08.015. Epub 2013 Aug 13.
5
2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺类作为强效 TRPV1 拮抗剂：2-氧代吡啶 C 区的结构活性关系。
Eur J Med Chem. 2013 Jun;64:589-602. doi: 10.1016/j.ejmech.2013.04.003. Epub 2013 Apr 11.
6
Screening TRPV1 antagonists for the treatment of pain: lessons learned over a decade.TRPV1 拮抗剂治疗疼痛的筛选：十余年的经验教训。
Expert Opin Drug Discov. 2009 Feb;4(2):159-80. doi: 10.1517/17460440802681300.
7
Multisteric TRPV1 nocisensor: a target for analgesics.多聚体 TRPV1 伤害感受器：镇痛药的作用靶点。
Trends Pharmacol Sci. 2012 Dec;33(12):646-55. doi: 10.1016/j.tips.2012.09.002. Epub 2012 Oct 12.
8
2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺作为有效的瞬时受体电位香草酸 1（TRPV1）拮抗剂：N-(6-三氟甲基吡啶-3-基甲基)C 区 2-氨基衍生物的结构活性关系。
J Med Chem. 2012 Oct 11;55(19):8392-408. doi: 10.1021/jm300780p. Epub 2012 Sep 20.
9
Targeting TRPV1 for pain relief: limits, losers and laurels.针对 TRPV1 缓解疼痛：限制、输家和胜利者。
Expert Opin Investig Drugs. 2012 Sep;21(9):1351-69. doi: 10.1517/13543784.2012.704021. Epub 2012 Jul 11.
10
TRPV1 activation is not an all-or-none event: TRPV1 partial agonism/antagonism and its regulatory modulation.TRPV1 的激活不是全有或全无的事件：TRPV1 部分激动剂/拮抗剂及其调节调控。
Curr Top Med Chem. 2011;11(17):2151-8. doi: 10.2174/156802611796904825.
Zotero 插件