4-(3-氨基丙基)-1-哌嗪羧酸苄酯 | 117009-98-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(3-氨基丙基)-1-哌嗪羧酸苄酯
• 中文别名: 4-(3-氨基丙基)哌嗪-1-羧酸苄酯
• 英文名称: 4-(3-Amino-propyl)-piperazine-1-carboxylic acid benzyl ester
• 英文别名: Benzyl 4-(3-aminopropyl)piperazine-1-carboxylate
• CAS: 117009-98-0
• 化学式: C₁₅H₂₃N₃O₂
• 分子量: 277.367
• InChiKey: BNRXWVARIROIGZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.133±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(1S,5S)-4-oxo-1-bicyclo[3.1.0]hexanyl]benzonitrile 、 4-(3-氨基丙基)-1-哌嗪羧酸苄酯 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 20.5h， 生成 4-{3-[(1R,2S,5R)-5-(4-Cyano-phenyl)-bicyclo[3.1.0]hex-2-ylamino]-propyl}-piperazine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas

  摘要：

  Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.

  DOI：

  10.1021/jm050886n

文献信息

• Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas
  作者：Mark D. McBriar、Henry Guzik、Sherry Shapiro、Jaroslava Paruchova、Ruo Xu、Anandan Palani、John W. Clader、Kathleen Cox、William J. Greenlee、Brian E. Hawes、Timothy J. Kowalski、Kim O'Neill、Brian D. Spar、Blair Weig、Daniel J. Weston、Constance Farley、John Cook

  DOI：10.1021/jm050886n

  日期：2006.4.1

  Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.