2-benzyl-4-morpholin-4-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine hydrochloride

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-benzyl-4-morpholin-4-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine hydrochloride
• 英文别名: 4-(2-benzyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)morpholine;hydrochloride
• 化学式: C₁₉H₂₄N₄O*ClH
• 分子量: 360.887
• InChiKey: FWGRRKLTOJXULM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.01
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  50.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯乙脒 在 吡啶 、 盐酸 、 sodium methylate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 19.0h， 生成 2-benzyl-4-morpholin-4-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine hydrochloride
  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

• Pyrimido [4,5-D] Azepine Derivatives As 5-HT2C Agonists
  申请人：Andrews Mark

  公开号：US20100113422A1

  公开（公告）日：2010-05-06

  The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof wherein the variables R 1 , R 2 , R 3a , R 3b , R 3b , R 3d , and R 100 are as defined herein. The invention is also directed to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a 5-HT 2c receptor-mediated disorders with a compound of formula (I) or a pharmaceutical composition comprising a compound of formula (I).

  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。
• US7928099B2
  申请人：——

  公开号：US7928099B2

  公开（公告）日：2011-04-19