tert-butyl 2-benzyl-4-(3-chlorophenylamino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate | 1443153-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: tert-butyl 2-benzyl-4-(3-chlorophenylamino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate
• CAS: 1443153-44-3
• 化学式: C₂₆H₂₉ClN₄O₂
• 分子量: 464.995
• InChiKey: VYXODGIXPWQCGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  67.35
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-benzyl-4-(3-chlorophenylamino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以29%的产率得到2-benzyl-N-(3-chlorophenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-4-amine
  参考文献：
  名称：

  Novel pyrimidoazepine analogs as serotonin 5-HT2A and 5-HT2C receptor ligands for the treatment of obesity

  摘要：

  Obesity is one of the most serious public health problems worldwide in the 21st century. Current therapeutic treatment for obesity is mostly focused on preventive measures involving dietary control and physical exercises in combination with anti-obesity medications. However, most of these anti-obesity medications have little or no effect on weight loss, and some cases have demonstrated fatal side effects. Due to the urgent need for highly potent and selective anti-obesity agents, the serotonin receptors (5-HTR) have been the focus of much interest as a novel therapeutic target. In this report, we have developed pyrimidoazepine analogs targeting the 5-HT2A and 5-HT2C receptors and evaluated their biological activity in vitro and in vivo as novel anti-obesity agents. We were able to identify 6p as the most potent 5-HT2A and 5-HT2C ligand in vitro (IC50 = 3 nM and 2.3 nM, respectively), and this compound also demonstrated the greatest potency in vivo. In an acute obesity model, mice treated with 6p showed significant decrease in body weight gain and food intake over approximately 77-94% compared to a control group. In a chronic obesity model, mice treated with 6p also showed a marked decrease in food intake and body weight gain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.020
• 作为产物：
  描述：

  苯乙脒 在 吡啶 、 sodium ethanolate 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 tert-butyl 2-benzyl-4-(3-chlorophenylamino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H)-carboxylate
  参考文献：
  名称：

  Novel pyrimidoazepine analogs as serotonin 5-HT2A and 5-HT2C receptor ligands for the treatment of obesity

  摘要：

  Obesity is one of the most serious public health problems worldwide in the 21st century. Current therapeutic treatment for obesity is mostly focused on preventive measures involving dietary control and physical exercises in combination with anti-obesity medications. However, most of these anti-obesity medications have little or no effect on weight loss, and some cases have demonstrated fatal side effects. Due to the urgent need for highly potent and selective anti-obesity agents, the serotonin receptors (5-HTR) have been the focus of much interest as a novel therapeutic target. In this report, we have developed pyrimidoazepine analogs targeting the 5-HT2A and 5-HT2C receptors and evaluated their biological activity in vitro and in vivo as novel anti-obesity agents. We were able to identify 6p as the most potent 5-HT2A and 5-HT2C ligand in vitro (IC50 = 3 nM and 2.3 nM, respectively), and this compound also demonstrated the greatest potency in vivo. In an acute obesity model, mice treated with 6p showed significant decrease in body weight gain and food intake over approximately 77-94% compared to a control group. In a chronic obesity model, mice treated with 6p also showed a marked decrease in food intake and body weight gain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.020