(9S)-6,7,8,9-四氢-N，9-二甲基-2-(苯甲基)-5H-嘧啶基[4,5-d]a庚烷-4-胺 | 1065110-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 中文名称: (9S)-6,7,8,9-四氢-N，9-二甲基-2-(苯甲基)-5H-嘧啶基[4,5-d]a庚烷-4-胺
• 英文名称: 2-benzyl-9-methyl-4-(methylamino)-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine
• 英文别名: (S)-2-benzyl-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine；PF-04479745；(9S)-2-benzyl-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine
• CAS: 1065110-43-1
• 化学式: C₁₇H₂₂N₄
• 分子量: 282.388
• InChiKey: IHHALLDEDARSAL-LBPRGKRZSA-N

物化性质

• 沸点：
  473.4±45.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

制备方法与用途

PF-4479745 是一种有效且选择性的 5-HT2C 受体激动剂（EC50: 10 nM，Ki: 15 nM）。这种化合物可应用于高血压等心血管疾病的科研研究中 [1]。

反应信息

• 作为反应物：
  描述：

  (9S)-6,7,8,9-四氢-N，9-二甲基-2-(苯甲基)-5H-嘧啶基[4,5-d]a庚烷-4-胺 、 酒石酸 以 甲醇 为溶剂， 以100%的产率得到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：

  苯乙脒 在 盐酸 、 三氟化硼乙醚 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (9S)-6,7,8,9-四氢-N，9-二甲基-2-(苯甲基)-5H-嘧啶基[4,5-d]a庚烷-4-胺
  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

文献信息

• WO2008/117169
  申请人：——

  公开号：——

  公开（公告）日：——
• Multiparameter Optimization in CNS Drug Discovery: Design of Pyrimido[4,5-<i>d</i>]azepines as Potent 5-Hydroxytryptamine 2C (5-HT_2C) Receptor Agonists with Exquisite Functional Selectivity over 5-HT_2A and 5-HT_2B Receptors
  作者：R. Ian Storer、Paul E. Brennan、Alan D. Brown、Peter J. Bungay、Kelly M. Conlon、Matthew S. Corbett、Robert P. DePianta、Paul V. Fish、Alexander Heifetz、Danny K. H. Ho、Alan S. Jessiman、Gordon McMurray、Cesar Augusto F. de Oliveira、Lee R. Roberts、James A. Root、Veerabahu Shanmugasundaram、Michael J. Shapiro、Melanie Skerten、Dominique Westbrook、Simon Wheeler、Gavin A. Whitlock、John Wright

  DOI：10.1021/jm5003292

  日期：2014.6.26

  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.