2-(1-azabicyclo<2.2.2>oct-3-yl)isoquinolin-1(2H)-one | 149653-82-7

• 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-(1-azabicyclo<2.2.2>oct-3-yl)isoquinolin-1(2H)-one
• 英文别名: 2-(1-azabicyclo[2.2.2.]oct-3-yl)-1(2H)-isoquinolinone；(RS)-2-(1-azabicyclo[2.2.2]oct-3-yl)-l(2H)-isoquinolinone；2-(1-azabicyclo[2.2.2]octan-3-yl)isoquinolin-1-one
• CAS: 149653-82-7
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: HPEMJEUFIDYINO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  溴 、 2-(1-azabicyclo<2.2.2>oct-3-yl)isoquinolin-1(2H)-one 在 二氯甲烷 、 disodium;carbonate 、 Sodium sulfate-III 、 乙醇 、 乙醚 作用下， 以 溶剂黄146 为溶剂， 以to give (RS)-2-(1-azabicyclo[2.2.2]oct-3-yl)-4-bromo-1(2H)-isoquinolinone (0.0832 g, 0.248 mmol), m.p. 208°-209° C.的产率得到(RS)-2-(1-azabicyclo[2.2.2 ]oct-3-yl)-4-bromo-1(2H)-isoquinolinone
  参考文献：
  名称：

  Isoquinolinone and dihydroisoquinolinone 5-HT.sub.3 receptor antagonists

  摘要：

  公式I中的5-HT.sub.3受体拮抗剂化合物：##STR1## 其中X和Y分别选自氢、卤素、羟基、较低的烷氧基、较低的烷基、硝基、氨基、氨基甲酰、（较低的烷基）氨基、二（较低的烷基）氨基和（较低的酰基）氨基；R.sup.1是氢、较低的烷基、苯基或卤素；R.sup.2是从式（a）、（b）、（c）和（d）中选择的基团：##STR2##

  公开号：

  US05491148A1
• 作为产物：
  描述：

  邻甲基苯甲酰氯 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 19.0h， 生成 2-(1-azabicyclo<2.2.2>oct-3-yl)isoquinolin-1(2H)-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

• US5491148A
  申请人：——

  公开号：US5491148A

  公开（公告）日：1996-02-13