N-[(1S)-1-[2-[4-[(3S,4R)-4-(4-chlorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]piperazin-1-yl]-5-methylphenyl]-2-methylpropyl]-3-(dimethylamino)propanamide | 851482-85-4

• 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: N-[(1S)-1-[2-[4-[(3S,4R)-4-(4-chlorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]piperazin-1-yl]-5-methylphenyl]-2-methylpropyl]-3-(dimethylamino)propanamide
• CAS: 851482-85-4
• 化学式: C₃₆H₅₂ClN₅O₃
• 分子量: 638.294
• InChiKey: XJIWJTAALOWWFJ-UKAHRKLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (4-(2-((S)-1-amino-2-methylpropyl)-4-methylphenyl)piperazin-1-yl)((3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl)methanone 、 N,N-二甲基-Β-丙氨酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以60%的产率得到N-[(1S)-1-[2-[4-[(3S,4R)-4-(4-chlorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]piperazin-1-yl]-5-methylphenyl]-2-methylpropyl]-3-(dimethylamino)propanamide
  参考文献：
  名称：

  Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor

  摘要：

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.115

文献信息

• Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor
  作者：Chen Chen、Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Stacy Markison、Jenny Wen、Ajay Madan、Sam R. Hoare、Alan C. Foster、Dragan Marinkovic、Caroline W. Chen、Melissa Arellano、John Saunders

  DOI：10.1016/j.bmcl.2007.10.115

  日期：2008.1

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.