methyl (3-endo)-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)acetate | 924646-52-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: methyl (3-endo)-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)acetate
• 英文别名: methyl 2-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)acetate；(3-endo)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-acetic acid methyl ester
• CAS: 924646-52-6
• 化学式: C₁₁H₁₉NO₂
• 分子量: 197.277
• InChiKey: XOOJYFHBANQQCP-ILWJIGKKSA-N

物化性质

• 沸点：
  249.8±13.0 °C(Predicted)
• 密度：
  1.029±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.42
• 重原子数：
  14.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl (3-endo)-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)acetate 在 四氯化锡 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二丁醚 、 丙酮 、 甲苯 为溶剂， 反应 25.75h， 生成 3-(8-(2-(benzyloxy)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile
  参考文献：
  名称：

  Development of Synthetic Routes, via a Tropinone Intermediate, to a Long-Acting Muscarinic Antagonist for the Treatment of Respiratory Disease

  摘要：

  This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.

  DOI：

  10.1021/op3002933
• 作为产物：
  描述：

  methyl (8-methyl-8-azabicyclo[3.2.1]oct-3-ylidene)acetate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、386.12 kPa 条件下， 反应 43.0h， 以11.2 g的产率得到methyl (3-endo)-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)acetate
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of Tropane Muscarinic Acetylcholine Receptor Antagonists

  摘要：

  Novel tropane derivatives were characterized as muscarinic acetylcholine receptor antagonists (mAChRs). Through optimization of the structure-activity relationship around the tropane scaffold, the quaternary ammonium salt 34 was identified as a very Potent M(3) mAChR antagonist. The compound was functionally active and displayed greater than 24 It duration of action in a mouse model of bronchoconstriction.

  DOI：

  10.1021/jm900736e

文献信息

• M3 Muscarinic Acetylcholine Receptor Antagonists
  申请人：Busch-Petersen Jakob

  公开号：US20080234315A1

  公开（公告）日：2008-09-25

  The present invention is directed to novel Muscarinic Acetylcholine receptor antagonists of Formula (I), pharmaceutical compositions and methods of using them. Compounds of Formula (I) are, inter alia, wherein: R1 and R2 are, independently, selected from the group consisting of 3-thienyl, pyridyl, benzyl, pyrimidyl, thiazolyl, isothiazolyl and C 3-7 cycloalkyl.

  本发明涉及一种新的肌动蛋白乙酰胆碱受体拮抗剂，其化学式为(I)，以及使用它们的药物组合物和方法。其中，化合物(I)包括但不限于以下结构：其中：R1和R2分别独立地选择自3-噻吩基、吡啶基、苄基、嘧啶基、噻唑基、异噻唑基和C3-7环烷基的群。
• WO2007/16650
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/16639
  申请人：——

  公开号：——

  公开（公告）日：——
• M3 MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1937230A2

  公开（公告）日：2008-07-02
• EP1937267A4
  申请人：——

  公开号：EP1937267A4

  公开（公告）日：2009-08-26