2-<(S)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-3-hydroxy-1-oxo-1H-benzisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-<(S)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-3-hydroxy-1-oxo-1H-benzisoquinoline
• 英文别名: 2-(1-azabicyclo[2.2.2]oct-3S-yl)-3-hydroxy-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one；2-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3-hydroxy-3a,4,5,6-tetrahydro-3H-benzo[de]isoquinolin-1-one
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: LKGBBKMVDUZQQY-KOHRHEQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-<(S)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-3-hydroxy-1-oxo-1H-benzisoquinoline 在 盐酸 作用下， 以 异丙醇 为溶剂， 生成 帕洛诺司琼
  参考文献：
  名称：

  Total Synthesis of the 5-HT3 Receptor Antagonist Palonosetron

  摘要：

  我们开发出了一条简捷高效的 5-HT3 受体拮抗剂 1 和 2（帕洛诺司琼）的合成路线。通过氢化、选择性硼氢化钠还原和脱水，对亚胺 7 的必要中心的氧化态进行了新的调整，得到了 1。亚胺 8 的硼氢化钠还原对 C-3 羧基和芳香环旁的 C-1 羧基具有选择性，从而得到羟基化合物 9。硼氢化钠还原过程中必须保持无氧，否则会产生二元醇 10a 和 10b，成为重要的副产品。

  DOI：

  10.1055/s-1996-4315
• 作为产物：
  描述：

  S-3-氨基奎宁环二盐酸盐 在 platinum(IV) oxide 氢气 作用下， 以 乙醇 、 异丙醇 为溶剂， 25.0 ℃ 、827.37 kPa 条件下， 反应 164.0h， 生成 2-<(S)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-3-hydroxy-1-oxo-1H-benzisoquinoline
  参考文献：
  名称：

  A Short Total Synthesis of Palonosetron Using Catalytic Hydrogenation

  摘要：

  DOI：

  10.3987/com-96-7444

文献信息

• PREPARATION OF CRYSTALLINE PALONOSETRON HYDROCHLORIDE
  申请人：Katkam Srinivas

  公开号：US20110213150A1

  公开（公告）日：2011-09-01

  Processes for the preparation of palonosetron hydrochloride and its crystalline forms.

  制备帕洛诺塞特龙盐酸盐及其结晶形式的工艺过程。
• NOVEL PALONOSETRON SALTS AND PROCESSES FOR PREPARATION AND PURIFICATION THEREOF
  申请人：Wensheng Tang

  公开号：US20100174080A1

  公开（公告）日：2010-07-08

  Provided are novel salts of 2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, methods of using such salts, and processes for producing such salts

  本发明提供了2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,3,3a,4,5,6-六氢-1H-苯[de]异喹啉-1-酮的新盐，以及使用这些盐的方法和制备这些盐的过程。
• 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists
  作者：Robin D. Clark、Aaron B. Miller、Jacob Berger、David B. Repke、Klaus K. Weinhardt、Bruce A. Kowalczyk、Richard M. Eglen、Douglas W. Bonhaus、Chi Ho Lee

  DOI：10.1021/jm00070a008

  日期：1993.9

  Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pK(i) values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pK(i) 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 mug/kg iv), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.
• PROCESS FOR THE PREPARATION OF 2-(1-AZABICYCLO(2.2.2)OCT-3-YL) -2,4,5,6-TETRAHYDRO-1H-BENZ(DE)ISOQUINOLIN-1-ONE AND INTERMEDIATE PRODUCT
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0770077B1

  公开（公告）日：2001-09-19
• US5567818A
  申请人：——

  公开号：US5567818A

  公开（公告）日：1996-10-22