(S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,3-dimethylbenzamide | 149653-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,3-dimethylbenzamide
• 英文别名: N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-dimethylbenzamide
• CAS: 149653-75-8
• 化学式: C₁₆H₂₂N₂O
• 分子量: 258.363
• InChiKey: AOAVFYZQHUSSBR-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,3-dimethylbenzamide 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-5-methyl-1(2H)-isoquinolinone
  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
• 作为产物：
  描述：

  2,3-二甲基苯甲酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 20.0h， 生成 (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,3-dimethylbenzamide
  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

• Isoquinolinone and dihydroisoquinolinone 5-HT.sub.3 receptor antagonists
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05491148A1

  公开（公告）日：1996-02-13

  5-HT.sub.3 receptor antagonist compounds of Formula I: ##STR1## in which X and Y are independently selected from hydrogen, halogen, hydroxy, lower alkoxy, lower alkyl, nitro, amino, aminocarbonyl, (lower alkyl)amino, di(lower alkyl)amino and (lower alkanoyl)amino; R.sup.1 is hydrogen, lower alkyl, phenyl or halogen; R.sup.2 is a group selected from Formulae (a), (b), (c) and (d): ##STR2##

  公式I中的5-HT.sub.3受体拮抗剂化合物：##STR1## 其中X和Y独立地选自氢、卤素、羟基、低级烷氧基、低级烷基、硝基、氨基、氨基甲酰、(低级烷基)氨基、二(低级烷基)氨基和(低级烷酰)氨基；R.sup.1是氢、低级烷基、苯基或卤素；R.sup.2是从公式(a)、(b)、(c)和(d)中选择的基团：##STR2##
• US5491148A
  申请人：——

  公开号：US5491148A

  公开（公告）日：1996-02-13