cis-3-{3-[3-(4-methylpiperazin-1-yl)propylamino]cyclopentyl}benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-3-{3-[3-(4-methylpiperazin-1-yl)propylamino]cyclopentyl}benzonitrile
• 英文别名: 3-[(1R,3S)-3-[3-(4-methylpiperazin-1-yl)propylamino]cyclopentyl]benzonitrile
• 化学式: C₂₀H₃₀N₄
• 分子量: 326.485
• InChiKey: AFCHWLBHYGJWPB-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  42.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cis-3-{3-[3-(4-methylpiperazin-1-yl)propylamino]cyclopentyl}benzonitrile 、 异氰酸- 3-氯-4-氟苯酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以79%的产率得到N'-(3-chloro-4-fluorophenyl)-N-[cis-3-(3-cyanophenyl)cyclopentyl]-N-[3-(4-methyl-1-piperazinyl)propyl]urea
  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
• 作为产物：
  描述：

  间溴苯甲腈 在 palladium on activated charcoal sodium tetrahydroborate 、 正丁基锂 、 cerium(III) chloride 、 四溴化碳 、 氢气 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， -78.0~100.0 ℃ 、101.33 kPa 条件下， 反应 40.75h， 生成 cis-3-{3-[3-(4-methylpiperazin-1-yl)propylamino]cyclopentyl}benzonitrile
  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