(2S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide | 691873-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide
• 英文别名: (2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide
• CAS: 691873-56-0
• 化学式: C₃₀H₂₉F₇N₂O
• 分子量: 566.562
• InChiKey: TWDSSLGDUOHXCF-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 以33%的产率得到(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide;hydrochloride
  参考文献：
  名称：

  [EN] GAMMA-AMINOAMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  [FR] MODULATEURS GAMMA-AMINOAMIDES DE L'ACTIVITE DE RECEPTEUR DE CHIMIOKINE

  摘要：

  本发明涉及式(I)的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R11、R12、W、X和n在此处定义，这些化合物可用作趋化因子受体活性的调节剂。特别是，这些化合物可用作趋化因子受体CCR-2的调节剂。

  公开号：

  WO2004041279A1
• 作为产物：
  描述：

  4-氟苯乙酸 在 4 A molecular sieve 、 (S)-(-)- α-甲基苄胺 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 臭氧 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 5.5h， 生成 (2S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide
  参考文献：
  名称：

  Novel, Orally Bioavailable γ-Aminoamide CC Chemokine Receptor 2 (CCR2) Antagonists

  摘要：

  Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).

  DOI：

  10.1021/jm060439n

文献信息

• Enantioselective Nickel‐Catalyzed Electrochemical Radical Allylation
  作者：Qinglin Zhang、Kang Liang、Chang Guo

  DOI：10.1002/anie.202210632

  日期：2022.9.19

  A highly enantioselective nickel-catalyzed electrochemical radical allylation reaction was developed in high yields with excellent enantiomeric ratios (up to 93 % ee). The single-electron transfer-based enantioselective electrocatalytic routes would be applied as an alternative approach for the development of a wide range of useful stereocontrolled reactions.

  以高产率开发了一种高度对映选择性的镍催化电化学自由基烯丙基化反应，具有优异的对映体比率（高达 93% ee）。基于单电子转移的对映选择性电催化路线将被用作开发各种有用的立体控制反应的替代方法。
• US7247725B2
  申请人：——

  公开号：US7247725B2

  公开（公告）日：2007-07-24
• [EN] GAMMA-AMINOAMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY<br/>[FR] MODULATEURS GAMMA-AMINOAMIDES DE L'ACTIVITE DE RECEPTEUR DE CHIMIOKINE
  申请人：MERCK & CO INC

  公开号：WO2004041279A1

  公开（公告）日：2004-05-21

  The present invention is directed to compounds of the formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R11, R12, W, X, and n are defined herein, which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.

  本发明涉及式(I)的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R11、R12、W、X和n在此处定义，这些化合物可用作趋化因子受体活性的调节剂。特别是，这些化合物可用作趋化因子受体CCR-2的调节剂。
• Novel, Orally Bioavailable γ-Aminoamide CC Chemokine Receptor 2 (CCR2) Antagonists
  作者：Alexander Pasternak、Dominick Marino、Pasquale P. Vicario、Julia Marie Ayala、Margaret A. Cascierri、William Parsons、Sander G. Mills、Malcolm MacCoss、Lihu Yang

  DOI：10.1021/jm060439n

  日期：2006.8.1

  Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).