ethyl 2-[3,5-difluoro-4-(methylsulfonylamino)phenyl]propionate | 1255042-12-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 2-[3,5-difluoro-4-(methylsulfonylamino)phenyl]propionate
• 英文别名: Ethyl 2-[3,5-difluoro-4-(methanesulfonamido)phenyl]propanoate
• CAS: 1255042-12-6
• 化学式: C₁₂H₁₅F₂NO₄S
• 分子量: 307.318
• InChiKey: FHGGQJWRNZIJJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-[3,5-difluoro-4-(methylsulfonylamino)phenyl]propionate 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-[3,5-difluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]methyl]propanamide
  参考文献：
  名称：

  Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl)propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3-(or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model.

  DOI：

  10.1016/j.bmcl.2018.05.043
• 作为产物：
  描述：

  2-氯丙酸乙酯 在 吡啶 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.34h， 生成 ethyl 2-[3,5-difluoro-4-(methylsulfonylamino)phenyl]propionate
  参考文献：
  名称：

  N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure–activity relationships in the A-region

  摘要：

  Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.008

文献信息

• Substituted Phenylureas and Phenylamides as Vanilloid Receptor Ligands
  申请人：FRANK Robert

  公开号：US20120258946A1

  公开（公告）日：2012-10-11

  Substituted phenylureas and phenylamides, processes for their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds for preparing pharmaceutical compositions.

  取代苯基脲和苯基酰胺，其制备过程，含有这些化合物的制药组合物以及使用这些化合物制备制药组合物的用途。
• [EN] SUBSTITUTED PHENYLUREAS AND PHENYLAMIDES AS VANILLOID RECEPTOR LIGANDS<br/>[FR] PHÉNYLURÉES ET PHÉNYLAMIDES SUBSTITUÉS EN TANT QUE LIGANDS DU RÉCEPTEUR VANILLOÏDE
  申请人：GRUENENTHAL GMBH

  公开号：WO2010127856A8

  公开（公告）日：2011-11-24
• SUBSTITUTED PHENYLUREAS AND PHENYLAMIDES AS VANILLOID RECEPTOR LIGANDS
  申请人：Medifron DBT Inc.

  公开号：EP2427435B1

  公开（公告）日：2017-06-14
• US8946204B2
  申请人：——

  公开号：US8946204B2

  公开（公告）日：2015-02-03
• US9120756B2
  申请人：——

  公开号：US9120756B2

  公开（公告）日：2015-09-01