3-(4-fluorobenzoyl)-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole | 103608-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(4-fluorobenzoyl)-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole
• 英文别名: (4-fluorophenyl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone
• CAS: 103608-85-1
• 化学式: C₂₂H₂₃FN₂O₂
• 分子量: 366.435
• InChiKey: JBOYTZZFBFXRRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  521.9±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-fluorobenzoyl)-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole 、 2-甲氧基乙胺 、 potassium carbonate 、 在 氮 、 二氯甲烷 、 Brine 、 magnesium sulfate 、 ethyl acetate-ether 作用下， 以 二甲基亚砜 为溶剂， 以afforded 4.2 g (37%) of 2-methyl-3-[4-(2-methoxyethylamino)benzoyl]-1-[2-(4-morpholinyl)ethyl]-1H-indole, m.p. 121°-123° C.的产率得到2-methyl-3-[4-(2-methoxyethylamino)benzoyl]-1-[2-(4-morpholinyl)ethyl]-1H-indole
  参考文献：
  名称：

  Method of use of 3-arylcarbonyl- and

  摘要：

  3-芳基羰基和3-环烷基羰基-1-氨基烷基-1H-吲哚是一种有用的镇痛、抗风湿和抗炎药物，通过将3-芳基羰基或3-环烷基羰基吲哚与氨基烷基卤化物在酸受体的存在下反应制备；通过在路易斯酸的存在下将1-氨基烷基-1H-吲哚与芳基羧酸卤化物或环烷基羧酸卤化物反应；或者通过将3-芳基羰基或3-环烷基羰基-1-对甲苯磺酰氧基烷基或卤代烷基-1H-吲哚与胺反应制备。

  公开号：

  US04885295A1
• 作为产物：
  描述：

  2-甲基吲哚 在 甲基溴化镁 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-fluorobenzoyl)-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole
  参考文献：
  名称：

  Antinociceptive (aminoalkyl)indoles

  摘要：

  The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) ''alpha-methylation'' caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported ''active'' conformations of the aroyl and related aromatic acetic acid derivatives. The H-1 NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD. The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.

  DOI：

  10.1021/jm00107a034

文献信息

• 3-Carbonyl-1-aminoalkyl-1H-indoles useful as analgesics and preparation thereof
  申请人：STERLING WINTHROP INC.

  公开号：EP0171037B1

  公开（公告）日：1992-06-17
• US4581354A
  申请人：——

  公开号：US4581354A

  公开（公告）日：1986-04-08
• US4634776A
  申请人：——

  公开号：US4634776A

  公开（公告）日：1987-01-06
• US4885295A
  申请人：——

  公开号：US4885295A

  公开（公告）日：1989-12-05
• US4978664A
  申请人：——

  公开号：US4978664A

  公开（公告）日：1990-12-18