5-amino-5-methyl-2,2-diphenyl-hexanenitrile hydrochloride | 1355532-89-6

• 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-amino-5-methyl-2,2-diphenyl-hexanenitrile hydrochloride
• 英文别名: 5-amino-5-methyl-2,2-diphenylhexanenitrile hydrochloride；5-Amino-5-methyl-2,2-diphenylhexanenitrile;hydrochloride
• CAS: 1355532-89-6
• 化学式: C₁₉H₂₂N₂*ClH
• 分子量: 314.858
• InChiKey: IKDMRGMCKKNECJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-amino-5-methyl-2,2-diphenyl-hexanenitrile hydrochloride 在 吡啶 、 sodium carbonate 、 potassium carbonate 、 potassium hydroxide 作用下， 以 二氯甲烷 、 3-甲基-3-戊醇 、 水 、 乙腈 为溶剂， 反应 42.75h， 生成 5-[3-(2-fluoro-3-methoxyphenoxy)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：

  4,4-dimethyl-[1,2,3]oxathiazinane 2,2-dioxide 在 4-二甲氨基吡啶 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.42h， 生成 5-amino-5-methyl-2,2-diphenyl-hexanenitrile hydrochloride
  参考文献：
  名称：

  Development of a Scaleable Synthesis of a Geminal Dimethyl Tertiary Amine as an Inhaled Muscarinic Antagonist for the Treatment of COPD

  摘要：

  An efficient and scalable process for the synthesis of muscarinic antagonist, PF-3635659 1, is described, illustrating redesign of an analogue-targeted synthesis which contained a scale-limiting rhodium-activated C H amination step. The final route includes a reproducible modified Bouveault reaction which has not previously been reported on a substrate of this complexity, or on such a scale with over 5 kg of the requisite gem-dimethylamine prepared via this methodology.

  DOI：

  10.1021/op200233r