1-((R)-1-(4-(2-((S)-1-amino-3-methylbutyl)-4-methylphenyl)piperazin-1-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)pyrrolidin-2-one | 956778-07-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-((R)-1-(4-(2-((S)-1-amino-3-methylbutyl)-4-methylphenyl)piperazin-1-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)pyrrolidin-2-one
• 英文别名: 1-[(2R)-1-[4-[2-[(1S)-1-amino-3-methylbutyl]-4-methylphenyl]piperazin-1-yl]-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl]pyrrolidin-2-one
• CAS: 956778-07-7
• 化学式: C₂₉H₃₈Cl₂N₄O₂
• 分子量: 545.552
• InChiKey: UINUKESLPATVPH-AHKZPQOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  69.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((R)-1-(4-(2-((S)-1-amino-3-methylbutyl)-4-methylphenyl)piperazin-1-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)pyrrolidin-2-one 、 N,N-二甲基-Β-丙氨酸 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 N-[(1S)-1-[2-[4-[(2R)-3-(2,4-dichlorophenyl)-2-(2-oxo-1-pyrrolidinyl)propionyl]-1-piperazinyl]-5-methylphenyl]-3-methylbutyl]-3-(dimethylamino)propanamide
  参考文献：
  名称：

  Pyrrolidinones as potent functional antagonists of the human melanocortin-4 receptor

  摘要：

  A series of pyrrolidinones derived from phenylalaninepiperazines were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor. In addition to their high binding affinities, these compounds displayed high functional potencies. 12a had a K-i of 0.94 nM in binding and IC50 of 21 nM in functional activity. 12a also demonstrated efficacy in a mouse cachexia model. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.097
• 作为产物：
  描述：

  (S)-N-[(1S)-1-[2-[4-[(2R)-3-(2,4-dichlorophenyl)-2-(2-oxopyrrolidin-1-yl)propanoyl]piperazin-1-yl]-5-methylphenyl]-3-methylbutyl]-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 1-((R)-1-(4-(2-((S)-1-amino-3-methylbutyl)-4-methylphenyl)piperazin-1-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)pyrrolidin-2-one
  参考文献：
  名称：

  Design, Synthesis, In Vitro, and In Vivo Characterization of Phenylpiperazines and Pyridinylpiperazines as Potent and Selective Antagonists of the Melanocortin-4 Receptor

  摘要：

  Benzylamine and pyridinemethylamine derivatives were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor (MC4R). These compounds were also profiled in rodents for their pharmacokinetic properties. Two compounds with diversified profiles in chemical structure, pharmacological activities, and pharmacokinetics, 10 and 12b, showed efficacy in an established murine cachexia model. For example, 12b had a K-i value of 3.4 nM at MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, including high brain penetration. Moreover, 12b was able to stimulate food intake in the tumor-bearing mice and reverse their lean body mass loss. Our results provided further evidence that a potent and selective MC4R antagonist with appropriate pharmacokinetic properties might potentially be useful for the treatment of cancer cachexia.

  DOI：

  10.1021/jm701137s