索利那新杂质29 | 861998-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 索利那新杂质29
• 英文名称: 4R-Hydroxysolifenacin
• 英文别名: 4-Hydroxy solifenacin, (4R)-；[(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S,4R)-4-hydroxy-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 861998-77-8
• 化学式: C₂₃H₂₆N₂O₃
• 分子量: 378.471
• InChiKey: LRNNBJBAUXSVMH-FKBYEOEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-quinuclidin-3-yl carbonochloridate hydrochloride 、 cis-4-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline 在 吡啶 作用下， 生成 索利那新杂质29 、 (-)-cis-(3'R)-quinuclidin-3'-yl 4-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
  参考文献：
  名称：

  Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1,2,3,4-Tetrahydroisoquinoline-2-carboxylate Derivatives as Novel Muscarinic Receptor Antagonists

  摘要：

  In the course of continuing efforts to develop potent and bladder-selective muscarinic M-3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M-2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.

  DOI：

  10.1021/jm050099q

文献信息

• Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1,2,3,4-Tetrahydroisoquinoline-2-carboxylate Derivatives as Novel Muscarinic Receptor Antagonists
  作者：Ryo Naito、Yasuhiro Yonetoku、Yoshinori Okamoto、Akira Toyoshima、Ken Ikeda、Makoto Takeuchi

  DOI：10.1021/jm050099q

  日期：2005.10.1

  In the course of continuing efforts to develop potent and bladder-selective muscarinic M-3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M-2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.