1-{2-[(1S)-amino-2-methylpropyl]-4-methylphenyl}-4-[(2R)-methyl-3-(2-fluoro-4-chlorophenyl)propionyl]piperazine | 956035-69-1

• 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-{2-[(1S)-amino-2-methylpropyl]-4-methylphenyl}-4-[(2R)-methyl-3-(2-fluoro-4-chlorophenyl)propionyl]piperazine
• 英文别名: (2R)-1-[4-[2-[(1S)-1-amino-2-methylpropyl]-4-methylphenyl]piperazin-1-yl]-3-(4-chloro-2-fluorophenyl)-2-methylpropan-1-one
• CAS: 956035-69-1
• 化学式: C₂₅H₃₃ClFN₃O
• 分子量: 446.008
• InChiKey: DHQLNQGLDLPYPC-KOSHJBKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{2-[(1S)-amino-2-methylpropyl]-4-methylphenyl}-4-[(2R)-methyl-3-(2-fluoro-4-chlorophenyl)propionyl]piperazine 、 叔丁氧羰酰基肌氨酸 在 碳酸氢钠 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以68%的产率得到1-{2-[(1S)-(methylaminoacetamido)-2-methylpropyl]-4-methylphenyl}-4-[(2R)-methyl-3-(2-fluoro-4-chlorophenyl)propionyl]piperazine
  参考文献：
  名称：

  Discovery of 1-{2-[(1S)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-phenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Melanocortin-4 Receptor for the Potential Treatment of Cachexia

  摘要：

  A potent and Selective antagonist of the melanocortin-4 receptor, 1-{2-[(IS)-(3-dimethylaminopropionyl)amino-2-methylpropyl}-6-methylphenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]pip- erazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration.

  DOI：

  10.1021/jm070806a
• 作为产物：
  描述：

  N-[(1S)-1-[2-[4-[(2R)-3-(4-chloro-2-fluorophenyl)-2-methylpropanoyl]piperazin-1-yl]-5-methylphenyl]-2-methylpropyl]-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 1-{2-[(1S)-amino-2-methylpropyl]-4-methylphenyl}-4-[(2R)-methyl-3-(2-fluoro-4-chlorophenyl)propionyl]piperazine
  参考文献：
  名称：

  Discovery of 1-{2-[(1S)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-phenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Melanocortin-4 Receptor for the Potential Treatment of Cachexia

  摘要：

  A potent and Selective antagonist of the melanocortin-4 receptor, 1-{2-[(IS)-(3-dimethylaminopropionyl)amino-2-methylpropyl}-6-methylphenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]pip- erazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration.

  DOI：

  10.1021/jm070806a

文献信息

• Discovery of 1-{2-[(1<i>S</i>)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-phenyl}-4-[(2<i>R</i>)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Melanocortin-4 Receptor for the Potential Treatment of Cachexia
  作者：Chen、Wanlong Jiang、Fabio Tucci、Joe A. Tran、Beth A. Fleck、Sam R. Hoare、Margaret Joppa、Stacy Markison、Jenny Wen、Yang Sai、Michael Johns、Ajay Madan、Takung Chen、Caroline W. Chen、Dragan Marinkovic、Melissa Arellano、John Saunders、Alan C. Foster

  DOI：10.1021/jm070806a

  日期：2007.11.1

  A potent and Selective antagonist of the melanocortin-4 receptor, 1-2-[(IS)-(3-dimethylaminopropionyl)amino-2-methylpropyl}-6-methylphenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]pip- erazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration.