N-(ethoxycarbonyl)-1H-indol-1-amine | 133054-78-1

• 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: N-(ethoxycarbonyl)-1H-indol-1-amine
• 英文别名: N-(1H-indol-1-yl) carbamic acid ethyl ester；N-(1H-indol-1-yl)-carbamic acid ethyl ester；ethyl N-indol-1-ylcarbamate
• CAS: 133054-78-1
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: FFCWOLJJKFTGNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  43.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(ethoxycarbonyl)-1H-indol-1-amine 在 sodium hydroxide 、 potassium tert-butylate 作用下， 以 乙二醇 为溶剂， 反应 10.0h， 生成 N-丙基吲哚-1-胺
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of N-Propyl-N-(4-pyridinyl)-1H-indol-1-amine (Besipirdine) and Related Analogs as Potential Therapeutic Agents for Alzheimer's Disease

  摘要：

  A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [H-3]quinuclidinyl benzilate binding, in. vivo reversal of scopolamine-induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [H-3]clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.

  DOI：

  10.1021/jm9506433
• 作为产物：
  描述：

  吲哚 、 alkaline earth salt of/the/ methylsulfuric acid 在 吡啶 、 氢氧化钾 、 hydroxylamine-O-sulfonic acid 作用下， 以 甲苯 为溶剂， 反应 2.25h， 生成 N-(ethoxycarbonyl)-1H-indol-1-amine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of N-Propyl-N-(4-pyridinyl)-1H-indol-1-amine (Besipirdine) and Related Analogs as Potential Therapeutic Agents for Alzheimer's Disease

  摘要：

  A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [H-3]quinuclidinyl benzilate binding, in. vivo reversal of scopolamine-induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [H-3]clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.

  DOI：

  10.1021/jm9506433

文献信息

• N-substituted-4-pyrimidinamines and pyrimidinediamines
  申请人：Hoechst-Roussell Pharmaceuticals, Inc.

  公开号：US04983608A1

  公开（公告）日：1991-01-08

  This invention relates to N-heteroaryl-4-pyrimidinamines of the formula ##STR1## where R.sub.1 is hydrogen, loweralkyl, aryl, or arylloweralkyl; R.sub.2 and R.sub.3 are independently hydrogen or loweralkyl, or R.sub.2 and R.sub.3 taken together are aryl; R.sub.4 and R.sub.5 are independently hydrogen or lowealkyl, or R.sub.4 and R.sub.5 taken together are aryl; X is hydrogen, halogen, cyano, nitro, amino, loweralkyl, loweralkoxy, trifluoromethyl or ##STR2## where Y is hydrogen, halogen or loweralkyl; m is an integer of 1 to 3; and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometrical and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as memory enhancing agents and as analgesic agents.

  该发明涉及公式##STR1##的N-杂环基-4-嘧啶胺，其中R.sub.1为氢、较低的烷基、芳基或芳基较低烷基；R.sub.2和R.sub.3分别为氢或较低的烷基，或R.sub.2和R.sub.3一起为芳基；R.sub.4和R.sub.5分别为氢或较低烷基，或R.sub.4和R.sub.5一起为芳基；X为氢、卤素、氰基、硝基、氨基、较低烷基、较低烷氧基、三氟甲基或##STR2##其中Y为氢、卤素或较低烷基；m为1至3的整数；以及其药用可接受的酸加盐，如适用的话，其几何和光学异构体及其混合物。该发明的化合物显示出作为增强记忆剂和镇痛剂的效用。
• N-heteroaryl-purin-6-amines useful as analgesic and anticonvulsant agents
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05017578A1

  公开（公告）日：1991-05-21

  This invention relates to a N-heteroaryl-purin-6-amine of the formula ##STR1## where R.sub.1 is hydrogen, lower alkyl, and arylloweralkyl; R.sub.2 and R.sub.3 are independently hydrogen, lower alkyl or R.sub.2 and R.sub.3 taken together are aryl; R.sub.4 and R.sub.5 are independently hydrogen, lower alkyl, or R.sub.4 and R.sub.5 taken together are aryl; R.sub.6 is hydrogen, lower alkyl, aryl, arylloweralkyl, ##STR2## where R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as defined above, and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic and anticonvulsant agents.

  本发明涉及一种具有以下结构的N-杂环芳基嘌呤-6-胺化合物：其中R.sub.1为氢、较低烷基和芳基较低烷基；R.sub.2和R.sub.3独立地为氢、较低烷基或R.sub.2和R.sub.3同时为芳基；R.sub.4和R.sub.5独立地为氢、较低烷基，或R.sub.4和R.sub.5同时为芳基；R.sub.6为氢、较低烷基、芳基、芳基较低烷基、其中R.sub.2、R.sub.3、R.sub.4和R.sub.5如上定义，以及其药学上可接受的酸盐，以及适用的几何和光学异构体和消旋混合物。本发明的化合物显示出作为镇痛和抗抽搐剂的效用。
• N-heteroaryl-purin-6-amines, and pharmaceutical compositions and methods
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05155098A1

  公开（公告）日：1992-10-13

  This invention relates to a N-heteroaryl-purin-6-amine of the formula ##STR1## where R.sub.1 is hydrogen, lower alkyl, and arylloweralkyl; R.sub.2 and R.sub.3 are independently hydrogen, lower alkyl or R.sub.2 and R.sub.3 taken together are aryl; R.sub.4 and R.sub.5 are independently hydrogen, lower alkyl, or R.sub.4 and R.sub.5 taken together are aryl; R.sub.6 is hydrogen, lower alkyl, aryl, arylloweralkyl, ##STR2## where R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as defined above, and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic and anitconvulsant agents.

  本发明涉及式为##STR1##的N-杂环芳基嘌呤-6-胺，其中R.sub.1为氢、低碳基和芳基低碳基；R.sub.2和R.sub.3独立地为氢、低碳基或R.sub.2和R.sub.3一起为芳基；R.sub.4和R.sub.5独立地为氢、低碳基或R.sub.4和R.sub.5一起为芳基；R.sub.6为氢、低碳基、芳基、芳基低碳基、##STR2##其中R.sub.2、R.sub.3、R.sub.4和R.sub.5如上所定义，以及其药学上可接受的酸加合物，适用时还包括其几何和光学异构体和外消旋混合物。本发明化合物具有镇痛和抗惊厥活性。
• N-heteroaryl-purin-6-amines, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0402752A1

  公开（公告）日：1990-12-19

  This invention relates to a N-heteroaryl-purin-6-amine of the formula where R₁ is hydrogen, lower alkyl, and arylloweralkyl; R₂ and R₃ are independently hydrogen, lower alkyl or R₂ and R₃ taken together are aryl; R₄ and R₅ are independently hydrogen, lower alkyl, or R₄ and R₅ taken together are aryl; R₆ is hydrogen, lower alkyl, aryl, arylloweralkyl, where R₂, R₃, R₄ and R₅ are as defined above, and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic and anticonvulsant agents.

  本发明涉及一种 N-杂芳基嘌呤-6-胺，其式如下 其中 R₁ 是氢、低级烷基和芳基低级烷基；R₂ 和 R₃ 独立地是氢、低级烷基或 R₂ 和 R₃ 合在一起是芳基；R₄ 和 R₅ 独立地是氢、低级烷基或 R₄ 和 R₅ 合在一起是芳基；R₆ 是氢、低级烷基、芳基、芳基低级烷基、 其中 R₂、R₃、R₄ 和 R₅ 如上文所定义，以及它们的药学上可接受的酸加成盐，并酌情包括它们的几何异构体、光学异构体和外消旋混合物。本发明的化合物可用作镇痛剂和抗惊厥剂。
• N-substituted-4-pyrimidinamines and -pyrimidindiamines, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0417584A2

  公开（公告）日：1991-03-20

  This invention relates to N-heteroaryl-4-pyrimidinamines of the formula where R₁ is hydrogen, loweralkyl, aryl, or arylloweralkyl; R₂ and R₃ are independently hydrogen or loweralkyl, or R₂ and R₃ taken together are aryl; R₄ and R₅ are independently hydrogen or loweralkyl, or R₄ and R₅ taken together are aryl; X is hydrogen, halogen, cyano, nitro, amino, loweralkyl, loweralkoxy, trifluoromethyl or where Y is hydrogen, halogen or loweralkyl; m is an integer of 1 to 3; and the pharmaceutically acceptable acid addition salts thereof and where applicable the geometrical and optical isomers and racemic mixtures thereof. The compounds of this invention display utility as memory enhancing agents and as analgesic agents.

  本发明涉及式中的 N-杂芳基-4-嘧啶胺 其中 R₁ 是氢、低级烷基、芳基或芳基低级烷基；R₂ 和 R₃ 独立地是氢或低级烷基，或 R₂ 和 R₃ 合在一起是芳基；R₄ 和 R₅ 独立地为氢或低级烷基，或 R₄ 和 R₅ 合在一起为芳基； X 为氢、卤素、氰基、硝基、氨基、低级烷基、低级烷氧基、三氟甲基或三氟乙烯基。 其中 Y 是氢、卤素或低级烷基；m 是 1 至 3 的整数；及其药学上可接受的酸加成盐，以及适当的几何异构体、光学异构体和外消旋混合物。本发明的化合物具有增强记忆和镇痛的作用。