1-{2-[(1S)-1-amino-2-methylpropyl]-6-fluorophenyl}-4-[(2R)-2-methyl-3-(2-methoxy-4-chlorophenyl)propionyl]piperazine trifluoroacetate | 1040411-51-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-{2-[(1S)-1-amino-2-methylpropyl]-6-fluorophenyl}-4-[(2R)-2-methyl-3-(2-methoxy-4-chlorophenyl)propionyl]piperazine trifluoroacetate
• CAS: 1040411-51-5
• 化学式: C₂HF₃O₂*C₂₅H₃₃ClFN₃O₂
• 分子量: 576.031
• InChiKey: ZSVPCHNNQYXYAC-KAPRSBACSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  96.1
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-{2-[(1S)-1-amino-2-methylpropyl]-6-fluorophenyl}-4-[(2R)-2-methyl-3-(2-methoxy-4-chlorophenyl)propionyl]piperazine trifluoroacetate 、 1-N-Boc-3-吖丁啶羧酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Pharmacological and pharmacokinetic characterization of 2-piperazine-α-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists

  摘要：

  A series of 2-piperazine-alpha-isopropylbenzylamine derivatives were synthesized and characterized as melanocortin-4 receptor (MC4R) antagonists. Attaching an amino acid to benzylamines 7 significantly increased their binding affinity, and the resulting compounds 8 - 12 bound selectively to MC4R over other melanocortin receptor subtypes and behaved as functional antagonists. These compounds were also studied for their permeability using Caco-2 cell monolayers and metabolic stability in human liver microsomes. Most compounds exhibited low permeability and high efflux ratio possibly due to their high molecular weights. They also showed moderate metabolic stability which might be associated with their moderate to high lipophilicity. Pharmacokinetic properties of these MC4R antagonists, including brain penetration, were studied in mice after oral and intravenous administrations. Two compounds identified to possess high binding affinity and selectivity, 10d and 11d, were studied in a murine cachexia model. After intraperitoneal (ip) administration of 1 mg/kg dose, mice treated with 10d had significantly more food intake and weight gain than the control animals, demonstrating efficacy by blocking the MC4 receptor. Similar in vivo effects were also observed when 11d was dosed orally at 20 mg/kg. These results provide further evidence that a potent and selective MC4R antagonist has potential in the treatment of cancer cachexia. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.072