(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(4-fluorophenyl)-5-oxopentanamide | 903512-73-2

• 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: (2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(4-fluorophenyl)-5-oxopentanamide
• CAS: 903512-73-2
• 化学式: C₂₀H₁₆F₇NO₂
• 分子量: 435.341
• InChiKey: GRLYRJNDJCXWRQ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.2
• 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)phenyl]methyl]-2-(4-fluorophenyl)-5-oxopentanamide 、 4-苯基哌啶 在 4 A molecular sieve 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 (S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(4-fluorophenyl)-5-(4-phenylpiperidin-1-yl)pentanamide
  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
• 作为产物：
  描述：

  4-氟苯乙酸 在 草酰氯 、 (S)-(-)- α-甲基苄胺 、 硼烷 、 1-羟基苯并三唑 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.25h， 生成 (2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(4-fluorophenyl)-5-oxopentanamide
  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

• 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).