N-(4-pyridinyl)-1H-indazol-1-amine | 121585-36-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: N-(4-pyridinyl)-1H-indazol-1-amine
• 英文别名: N-pyridin-4-ylindazol-1-amine
• CAS: 121585-36-2
• 化学式: C₁₂H₁₀N₄
• 分子量: 210.238
• InChiKey: FVGVWOXQWDAFTQ-UHFFFAOYSA-N

物化性质

• 沸点：
  406.6±37.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溴丙烷 、 N-(4-pyridinyl)-1H-indazol-1-amine 在 sodium hydride 作用下， 生成 N-(Propyl)-N-(4-pyridinyl)-1H-indazol-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
• 作为产物：
  描述：

  吲唑 在 氢氧化钾 、 hydroxylamine-O-sulfonic acid 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 生成 N-(4-pyridinyl)-1H-indazol-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

• Pyrazol and indazolpyridinamines
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04806554A1

  公开（公告）日：1989-02-21

  There are described compounds of the formula ##STR1## where n is 0 or 1; R.sub.1 is independently hydrogen, loweralkyl, loweralkenyl, loweralkynyl, loweralkoxycarbonylloweralkyl, loweralkylaminocarbonylloweralkyl, aminocarbonylloweralkyl, arylloweralkyl, phenyl, nitrophenyl, cyanophenyl, trifluoromethylphenyl, aminophenyl, loweralkanoylaminophenyl, loweralkoxycarbonyl, arylloweralkoxycarbonyl, aryloxycarbonyl, loweralkylaminocarbonyl, arylloweralkylaminocarbonyl, arylaminocarbonyl, alkanoyl, arylloweralkanoyl, aroyl, alkenoyl, alkynoyl or --R.sub.5 --NR'R" where R.sub.5 is loweralkylene, loweralkenylene or loweralkynylene and R' and R" are each independently loweralkyl or alternatively the group --NR'R" as a whole is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 4-loweralkyl-1-piperazinyl or 4-aryl-1-piperazinyl; R.sub.2 is hydrogen or loweralkyl; R.sub.3 and R.sub.4 are each independently hydrogen or loweralkyl, or alternatively R.sub.3 and R.sub.4 taken together form --CH.dbd.CH--CH.dbd.CH-- so that the moiety ##STR2## becomes an indazole ring; and X is hydrogen, nitro, amino, halogen, loweralkanoylamino, arylloweralkanoylamino, aroylamino, alkylamino, arylloweralkylamino, loweralkyl, and cyano; which compounds are useful as analgesic and antidepressant agents.

  描述了以下化合物的公式：##STR1## 其中n为0或1；R.sub.1独立地为氢、低碳基、低烯基、低炔基、低氧羰基低碳基、低氨基羰基低碳基、氨基羰基低碳基、芳基低碳基、苯基、硝基苯基、氰基苯基、三氟甲基苯基、氨基苯基、低烷酰胺基苯基、低氧羰基芳基低碳基、芳基氧羰基、低碳基氨基羰基、芳基低碳基氨基羰基、芳基氨基羰基、烷酰基、芳基低烷酰基、芳基酰基、烯酰基、炔酰基或--R.sub.5--NR'R"，其中R.sub.5为低碳基亚烷基、低烯基亚烷基或低炔基亚烷基，R'和R"各自独立地为低碳基或作为整体的--NR'R"为1-吡咯烷基、1-哌啶基、4-吗啉基、4-低烷基-1-哌嗪基或4-芳基-1-哌嗪基；R.sub.2为氢或低碳基；R.sub.3和R.sub.4各自独立地为氢或低碳基，或者R.sub.3和R.sub.4结合成--CH.dbd.CH--CH.dbd.CH--，使得##STR2##成为吲哚唑环；X为氢、硝基、氨基、卤素、低烷酰胺基、芳基低烷酰胺基、芳基酰胺基、烷基氨基、芳基低烷基氨基、低碳基和氰基；这些化合物可用作镇痛和抗抑郁剂。
• Pyrazol- and indazolpyridin amines, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0324359A1

  公开（公告）日：1989-07-19

  There are described compounds of the formula where n is 0 or 1; R₁ is independently hydrogen, loweralkyl, loweralkenyl, loweralkynyl, loweralkoxycarbonylloweralkyl, loweralkylaminocarbonylloweralkyl, aminocarbonylloweralkyl, arylloweralkyl, phenyl, nitrophenyl, cyanophenyl, trifluoromethylphenyl, aminophenyl, loweralkanoylaminophenyl, loweralkoxycarbonyl, arylloweralkoxycarbonyl, aryloxycarbonyl, loweralkylaminocarbonyl, arylloweralkylaminocarbonyl, arylaminocarbonyl, alkanoyl, arylloweralkanoyl, aroyl, alkenoyl, alkynoyl or -R₅-NR′R˝ where R₅ is loweralkylene, loweralkenylene or loweralkynylese and R′ and R˝ are each independently loweralkyl or alternatively the group -NR′R˝ as a whole is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 4-loweralkyl-1-piperazinyl or 4-aryl-1-piperazinyl; R₂ is hydrogen or loweralkyl; R₃ and R₄ are each independently hydrogen of loweralkyl, or alternatively R₃ and R₄ taken together form -CH=CH-CH=CH- so that the moiety becomes an indazole ring; and X is hydrogen, nitro, amino, halogen, loweralkanoylamino, arylloweralkanoylamino, aroylamino, alkylamino, arylloweralkylamino, loweralkyl, and cyano; and a process for their preparation. The compounds or the invention are useful as analgesic and antidepressant agents.

  所述化合物的化学式为 其中 n 为 0 或 1； R₁独立地为氢、低级烷基、低级烯基、低级炔基、低级烷氧基羰基、低级烷基氨基羰基、低级烷基氨基羰基、低级芳烷基、苯基、硝基苯基、氰苯基、三氟甲基苯基、氨基苯基、低级烷酰基氨基苯基、低级烷氧基羰基、芳低级烷氧基羰基、芳氧基羰基、低级烷基氨基羰基、芳基低级烷基氨基羰基、芳基氨基羰基、烷酰基、芳基低级烷酰基、芳基、烯酰基、炔酰基或 -R₅-NR′R˝，其中 R₅ 是低级烯烃、R′和 R˝各自独立地为低级烷基，或者基团 -NR′R˝ 整体为 1-吡咯烷基、1-哌啶基、4-吗啉基、4-低级烷基-1-哌嗪基或 4-芳基-1-哌嗪基； R₂ 是氢或低级烷基； R₃ 和 R₄ 各自独立地为低级烷基中的氢，或者 R₃ 和 R₄ 合在一起形成 -CH=CH-CH=CH-，从而使分子 成为吲唑环；以及 X 是氢、硝基、氨基、卤素、低级烷酰氨基、芳基低级烷酰氨基、芳基氨基、烷基氨基、芳基低级烷基氨基、低级烷基和氰基；及其制备方法。本发明的化合物可用作镇痛剂和抗抑郁剂。
• US4806554A
  申请人：——

  公开号：US4806554A

  公开（公告）日：1989-02-21
• Synthesis and Structure−Activity Relationships of <i>N</i>-Propyl-<i>N</i>-(4-pyridinyl)-1<i>H</i>-indol-1-amine (Besipirdine) and Related Analogs as Potential Therapeutic Agents for Alzheimer's Disease
  作者：Joseph T. Klein、Larry Davis、Gordon E. Olsen、George S. Wong、Francis P. Huger、Craig P. Smith、Wayne W. Petko、Michael Cornfeldt、Jeffrey C. Wilker、R. D. Blitzer、E. Landau、V. Haroutunian、Lawrence L. Martin、Richard C. Effland

  DOI：10.1021/jm9506433

  日期：1996.1.1

  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.