tert-butyl 2-benzyl-9-(rac)-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate | 1613666-25-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: tert-butyl 2-benzyl-9-(rac)-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
• CAS: 1613666-25-3
• 化学式: C₂₂H₃₀N₄O₂
• 分子量: 382.506
• InChiKey: QKAWPESEVJPCOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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-9-(rac)-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-benzyl-9-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine
  参考文献：
  名称：

  Multiparameter Optimization in CNS Drug Discovery: Design of Pyrimido[4,5-d]azepines as Potent 5-Hydroxytryptamine 2C (5-HT_2C) Receptor Agonists with Exquisite Functional Selectivity over 5-HT_2A and 5-HT_2B Receptors

  摘要：

  A series of 4-substituted pyrimido[4,5-d]azepines that are potent, selective 5-HT2C receptor partial agonists is described. A rational medicinal chemistry design strategy to deliver CNS penetration coupled with SAR-based optimization of selectivity and agonist potency provided compounds with the desired balance of preclinical properties. Lead compounds 17 (PF-4479745) and 18 (PF-4522654) displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems. Utilizing recent advances in the structural biology of GPCRs, homology modeling has been carried out to rationalize binding and agonist efficacy of these compounds.

  DOI：

  10.1021/jm5003292
• 作为产物：
  描述：

  重氮乙酸乙酯 、 3-甲基-4-氧代哌啶-1-羧酸叔丁酯 、 三氟甲磺酸酐 、 苯乙脒 、 甲胺 在 三氟化硼乙醚 、 sodium methylate 作用下， 以 乙醚 、 甲醇 为溶剂， 反应 18.0h， 生成 tert-butyl 2-benzyl-9-(rac)-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate 、 tert-butyl 2-benzyl-9-(rac)-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
  参考文献：
  名称：

  Multiparameter Optimization in CNS Drug Discovery: Design of Pyrimido[4,5-d]azepines as Potent 5-Hydroxytryptamine 2C (5-HT_2C) Receptor Agonists with Exquisite Functional Selectivity over 5-HT_2A and 5-HT_2B Receptors

  摘要：

  A series of 4-substituted pyrimido[4,5-d]azepines that are potent, selective 5-HT2C receptor partial agonists is described. A rational medicinal chemistry design strategy to deliver CNS penetration coupled with SAR-based optimization of selectivity and agonist potency provided compounds with the desired balance of preclinical properties. Lead compounds 17 (PF-4479745) and 18 (PF-4522654) displayed robust pharmacology in a preclinical canine model of stress urinary incontinence (SUI) and no measurable functional agonism at the key selectivity targets 5-HT2A and 5-HT2B in relevant tissue-based assay systems. Utilizing recent advances in the structural biology of GPCRs, homology modeling has been carried out to rationalize binding and agonist efficacy of these compounds.

  DOI：

  10.1021/jm5003292