5-{3-[2-(benzyloxy)phenoxy]azetidin-1-yl}-5-methyl-2,2-diphenylhexanenitrile | 931410-14-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-{3-[2-(benzyloxy)phenoxy]azetidin-1-yl}-5-methyl-2,2-diphenylhexanenitrile
• 英文别名: 5-Methyl-2,2-diphenyl-5-[3-(2-phenylmethoxyphenoxy)azetidin-1-yl]hexanenitrile
• CAS: 931410-14-9
• 化学式: C₃₅H₃₆N₂O₂
• 分子量: 516.683
• InChiKey: MPOXPPCMDTVNIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-{3-[2-(benzyloxy)phenoxy]azetidin-1-yl}-5-methyl-2,2-diphenylhexanenitrile 在 20 % Pd(OH)2/C 、 甲酸铵 、 potassium hydroxide 作用下， 以 乙醇 、 3-甲基-3-戊醇 为溶剂， 反应 22.0h， 生成 5-[3-(2-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide
  参考文献：
  名称：

  Inhalation by Design: Novel Tertiary Amine Muscarinic M₃ Receptor Antagonists with Slow Off-Rate Binding Kinetics for Inhaled Once-Daily Treatment of Chronic Obstructive Pulmonary Disease

  摘要：

  A novel tertiary amine series of potent muscarinic M-3 receptor antagonists are described that exhibit potential as inhaled long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease. Geminal dimethyl functionality present in this series of compounds confers very long dissociative half-life (slow off-rate) from the M-3 receptor that mediates very long-lasting smooth muscle relaxation in guinea pig tracheal strips. Optimization of pharmacokinetic properties was achieved by combining rapid oxidative clearance with targeted introduction of a phenolic moiety to secure rapid glucuronidation. Together, these attributes minimize systemic exposure following inhalation, mitigate potential drug-drug interactions, and reduce systemically mediated adverse events. Compound 47 (PP-3635659) is identified as a Phase II clinical candidate from this series with in vivo duration of action studies confirming its potential for once-daily use in humans.

  DOI：

  10.1021/jm200884j
• 作为产物：
  描述：

  甲基氯化镁 在 氯化锆(IV) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以10%的产率得到5-{3-[2-(benzyloxy)phenoxy]azetidin-1-yl}-5-methyl-2,2-diphenylhexanenitrile
  参考文献：
  名称：

  WO2007/34325

  摘要：

  公开号：

文献信息

• Carboxamide derivatives as muscarinic receptor antagonists
  申请人：Glossop Alan Paul

  公开号：US20070105831A1

  公开（公告）日：2007-05-10

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有下列公式的化合物、其制备方法和中间体，以及包含它们的抗胆碱能药物组合物。
• Carboxamide Derivatives As Muscarinic Receptor Antagonists
  申请人：Glossop Paul Alan

  公开号：US20100029720A1

  公开（公告）日：2010-02-04

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有以下式的化合物，以及制备它们的过程和中间体，它们作为毒蕈碱受体拮抗剂的用途和包含它们的制药组合物。
• CARBOXAMIDE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP1928821B1

  公开（公告）日：2009-01-07
• US7772223B2
  申请人：——

  公开号：US7772223B2

  公开（公告）日：2010-08-10
• US8268881B2
  申请人：——

  公开号：US8268881B2

  公开（公告）日：2012-09-18