| 1051926-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• CAS: 1051926-95-4
• 化学式: C₁₈H₃₁N₃OS
• 分子量: 337.53
• InChiKey: JJLRLILDTPAGGQ-SBUREZEXSA-N

反应信息

• 作为反应物：
  描述：

  、 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， 生成
  参考文献：
  名称：

  Design and synthesis of 3-arylpyrrolidine-2-carboxamide derivatives as melanocortin-4 receptor ligands

  摘要：

  Based on 3-phenylpropionamides, a series of 3-arylpyrrolidine-2-carboxamide derivatives was designed and synthesized to study the effect of cyclizations as melanocortin-4 receptor ligands. It was found that the 2R, 3R-pyrrolidine isomer possessed the most potent affinity among the four stereoisomers. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.125

文献信息

• Pharmacological and pharmacokinetic characterization of 2-piperazine-α-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists
  作者：Chen Chen、Fabio C. Tucci、Wanlong Jiang、Joe A. Tran、Beth A. Fleck、Sam R. Hoare、Jenny Wen、Takung Chen、Michael Johns、Stacy Markison、Alan C. Foster、Dragan Marinkovic、Caroline W. Chen、Melissa Arellano、John Harman、John Saunders、Haig Bozigian、Daniel Marks

  DOI：10.1016/j.bmc.2008.03.072

  日期：2008.5

  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.