tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate | 1065113-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
• 英文别名: tert-butyl 2-benzyl-9-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate；Tert-butyl 2-benzyl-9-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate；tert-butyl 2-benzyl-9-methyl-4-oxo-5,6,8,9-tetrahydro-3H-pyrimido[4,5-d]azepine-7-carboxylate
• CAS: 1065113-32-7
• 化学式: C₂₁H₂₇N₃O₃
• 分子量: 369.464
• InChiKey: RDOHWUUABJHNNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate 、 苯乙脒 在 tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate 作用下， 以yielding 70% of title compound的产率得到tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
  参考文献：
  名称：

  Pyrimido [4,5-D] Azepine Derivatives As 5-HT2C Agonists

  摘要：

  本发明提供了式（I）的化合物：或其药学上可接受的盐，其中变量R1、R2、R3a、R3b、R3b、R3d和R100如本文所定义。本发明还涉及包括式（I）化合物的制药组合物，以及使用式（I）的化合物或包括式（I）的制药组合物治疗5-HT2c受体介导的疾病的方法。

  公开号：

  US20100113422A1
• 作为试剂：
  描述：

  1-tert-butyl 4-ethyl-6-(rac)-methyl-5-oxoazepine-1,4-dicarboxylate 、 苯乙脒 在 tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate 作用下， 以yielding 70% of title compound的产率得到tert-butyl 2-benzyl-9-(rac)-methyl-4-oxo-3,4,5,6,8,9-hexahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate
  参考文献：
  名称：

  Pyrimido [4,5-D] azepine derivatives as 5-HT2c agonists

  摘要：

  本发明提供一种式子(I)的化合物或其药学上可接受的盐，其中变量R1、R2、R3a、R3b、R3b、R3d和R100的定义如本文所述。本发明还涉及包含式子(I)化合物的药物组合物以及使用式子(I)化合物或包含式子(I)化合物的药物组合物治疗5-HT2c受体介导的疾病的方法。

  公开号：

  US07928099B2

文献信息

• 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.
• US7928099B2
  申请人：——

  公开号：US7928099B2

  公开（公告）日：2011-04-19
• [EN] PYRIMIDO [4, 5-D] AZEPINE DERIVATIVES AS 5-HT2C AGONISTS<br/>[FR] DÉRIVÉS PYRIMIDO [4,5-D] AZÉPINE COMME ANTAGONISTES DU 5-HT2C
  申请人：PFIZER LTD

  公开号：WO2008117169A1

  公开（公告）日：2008-10-02

  [EN] The present invention relates to compounds of formula (I): wherein R¹, R², R^3a,^{R3b, R3c, R3d and R100 are as defined in the specification. These compounds act as 5-HT_2C agonists.
  [FR] La présente invention concerne des composés de formule (I) : R1, R2, R3a,R3b, R3c, R3d et R100 étant tels que définis dans la spécification. Ces composés agissent comme des antagonistes du 5-HT_2C.}