(3aS)-2-<(R)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-1H-benzisoquinolin-1-one | 149654-00-2

• 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: (3aS)-2-<(R)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-1H-benzisoquinolin-1-one
• 英文别名: 2-(1-azabicyclo-[2.2.2]oct-3R-yl)-2,3,3aS,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one；Palonosetron, (3R)-；(3aS)-2-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3H-benzo[de]isoquinolin-1-one
• CAS: 149654-00-2
• 化学式: C₁₉H₂₄N₂O
• 分子量: 296.412
• InChiKey: CPZBLNMUGSZIPR-WBVHZDCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 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：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-<(R)-1-azabicyclo<2.2.2>oct-3-yl>-5,6,7,8-tetrahydronaphthalene-1-carboxamide 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 氢气 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 361.0h， 生成 (3aS)-2-<(R)-1-azabicyclo<2.2.2>oct-3-yl>-2,3,3a,4,5,6-hexahydro-1H-benzisoquinolin-1-one
  参考文献：
  名称：

  2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists

  摘要：

  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.

  DOI：

  10.1021/jm00070a008

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。
• SOFT CAPSULES COMPRISING PALONOSETRON HYDROCHLORIDE HAVING IMPROVED STABILITY AND BIOAVAILABILITY
  申请人：Helsinn Healthcare S.A.

  公开号：EP1940366B1

  公开（公告）日：2009-04-08
• Dosage Forms of Palonosetron Hydrochloride Having Improved Stability and Bioavailability
  申请人：Bonadeo Daniele

  公开号：US20080152704A1

  公开（公告）日：2008-06-26

  Provided are solid oral dosage forms of palonosetron hydrochloride, methods of using the dosage forms to treat emesis, and methods of making the dosage forms. The dosage forms have improved stability and bioavailability, and are preferably in the form of liquid filled capsules.
• DOSAGE FORMS OF PALONOSETRON HYDROCHLORIDE HAVING IMPROVED STABILITY AND BIOAVAILABILITY
  申请人：Helsinn Healthcare SA

  公开号：US20170035748A1

  公开（公告）日：2017-02-09

  Provided are solid oral dosage forms of palonosetron hydrochloride, methods of using the dosage forms to treat emesis, and methods of making the dosage forms. The dosage forms have improved stability and bioavailability, and are preferably in the form of liquid filled capsules.
• US5202333A
  申请人：——

  公开号：US5202333A

  公开（公告）日：1993-04-13