5-methoxy-3-(1-piperazinyl)-1H-indazole | 131634-54-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-methoxy-3-(1-piperazinyl)-1H-indazole
• 英文别名: 5-methoxy-3-piperazin-1-yl-1H-indazole
• CAS: 131634-54-3
• 化学式: C₁₂H₁₆N₄O
• 分子量: 232.285
• InChiKey: KZQHKKCYKKKVKS-UHFFFAOYSA-N

物化性质

• 熔点：
  163-169 °C
• 沸点：
  466.5±35.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  53.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-3-(1-piperazinyl)-1H-indazole 、 氯甲酸苄酯 在 lanthanum(III) nitrate 作用下， 反应 0.17h， 以96%的产率得到benzyl 4-(5-methoxy-1H-indazol-3-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  A mild and efficient chemoselective protection of amines as N-benzyloxycarbonyl derivatives in the presence of La(NO3)3·6H2O under solvent-free conditions

  摘要：

  A facile and versatile method for the chemoselective N-benzyloxycarbonylation of amines has been developed by treatment with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of lanthanum(III) nitrate hexahydrate under solvent-free conditions. The method is general for the preparation of N-Cbz derivatives of aliphatic (acyclic and cyclic) and aromatic amines. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.11.015
• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲酸乙酯 在 吡啶 、 copper(l) iodide 、 氯化亚砜 、 potassium carbonate 、 potassium hydroxide 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 异丙醇 为溶剂， 反应 26.5h， 生成 5-methoxy-3-(1-piperazinyl)-1H-indazole
  参考文献：
  名称：

  千量级异二氢吲哚类化合物制备工艺改进

  摘要：

  准备了一系列带有吲唑（HMR 2934、HMR 2651）或苯并异恶唑（HMR 2543）附件的异吲哚啉类似物，用于治疗强迫症和注意力缺陷障碍等精神疾病。通过用 LiAlH4 还原相应的邻苯二甲酰亚胺来制备异二氢吲哚化合物。一种化合物不是手性的，另外两种需要对映选择性合成。这些光学活性类似物的关键步骤涉及通过 SN2 过程将哌嗪基中间体或哌啶基中间体与 3-苄氧基-2-三氟甲磺酸基丙酸甲酯偶联。这两种类似物的产品具有 >98% ee。工艺改进导致每种化合物的合成量达到数公斤。

  DOI：

  10.1021/op020225p

文献信息

• 3-(1-substituted-4-piperazinyl)-1H-indazoles
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04954503A1

  公开（公告）日：1990-09-04

  This invention relates to 3-(1-substituted-4-piperazinyl)-1H-indazoles having the following formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, and phenylsulfonyl: and R.sub.2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula ##STR2## where Z is selected from hydrogen, halogen, loweralkoxy, CF.sub.3, NO.sub.2, and NH.sub.2 ; ##STR3## where Z is as defined above; ##STR4## where Z is as defined above; ##STR5## where R.sub.3 and R.sub.4 are each independently hydrogen and loweralkyl; ##STR6## where Z is as defined above; ##STR7## where R' and R" are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF.sub.3, NO.sub.2 and amino; n is an integer of 1 to 4, with the further proviso that R.sub.2 is not loweralkyl when R.sub.1 is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof and where appropriate the geometric isomers, the stereoisomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic and antipsychotic agents.

  本发明涉及具有以下通式结构的3-(1-取代-4-哌嗪基)-1H-吲唑类化合物：##STR1## 其中R1为氢、低级烷基、芳基低级烷基、酰基、环烷基低级亚烷基和苯磺酰基；R2为氢、低级烷基、羟基低级烷基，其结构式为##STR2## 其中Z选自氢、卤素、低级烷氧基、CF3、NO2和NH2；##STR3## 其中Z如上定义；##STR4## 其中Z如上定义；##STR5## 其中R3和R4各自独立为氢和低级烷基；##STR6## 其中Z如上定义；##STR7## 其中R'和R"各自独立为氢和低级烷基；X为氢、低级烷基、羟基、卤素、低级烷氧基、CF3、NO2和氨基；n为1至4的整数，但当R1为氢或酰基且X为氯时，R2不应当为低级烷基；其药学上可接受的酸加成盐，以及适当时的几何异构体、立体异构体和外消旋混合物。本发明的化合物显示出作为镇痛剂和抗精神病药物的效用。
• 3-(1-Substituted-4-piperazinyl)-1H-indazoles
  申请人：Hoechst-Roussel Pharmaceuticals Incorporated

  公开号：US05077405A1

  公开（公告）日：1991-12-31

  This invention relates to 3-(1-substituted-4-piperazinyl)-1H-indazoles having the following formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, and phenylsulfonyl; and R.sub.2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula -(loweralkylene)-OH, arylloweralkyl, acyl, cycloalkylloweralkylene, ##STR2## where Z is selected from hydrogen, halogen, loweralkoxy, CF.sub.3, NO.sub.2, and NH.sub.2 ; ##STR3## where Z is as defined above; ##STR4## where Z is as defined above; ##STR5## where R.sub.3 and R.sub.4 are each independently hydrogen and loweralkyl; ##STR6## where Z is as defined above; ##STR7## where R' and R" are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF.sub.3, NO.sub.2 and amino; n is an integer of 1 to 4, with the further proviso that R.sub.2 is not loweralkyl when R.sub.1 is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof and where appropriate the geometric isomers, the stereoisomers and racemic mixtures thereof. The compounds of this invention display utility as analgesic and antipsychotic agents.

  本发明涉及具有以下式子的3-(1-取代的4-哌嗪基)-1H-吲唑：##STR1## 其中R.sub.1是氢、低碳基、芳基低碳基、酰基、环烷基低碳基亚烷基和苯基磺酰基；R.sub.2是氢、低碳基、-(低碳基亚烷基)-OH的羟基低碳基、芳基低碳基、酰基、环烷基低碳基亚烷基、##STR2## 其中Z选择自氢、卤素、低碳氧基、CF.sub.3、NO.sub.2和NH.sub.2；##STR3## 其中Z如上所定义；##STR4## 其中Z如上所定义；##STR5## 其中R.sub.3和R.sub.4各自独立地为氢和低碳基；##STR6## 其中Z如上所定义；##STR7## 其中R'和R"各自独立地为氢和低碳基；X是氢、低碳基、羟基、卤素、低碳氧基、CF.sub.3、NO.sub.2和氨基；n是1到4的整数，进一步规定当R.sub.1为氢或酰基且X为氯时，R.sub.2不是低碳基；所述化合物的药学上可接受的酸加成盐，以及必要时的几何异构体、立体异构体和外消旋混合物。本发明的化合物显示出作为镇痛剂和抗精神病药物的效用。
• THIENOISOXAZOLYL-AND THIENYLPYRRAZOLYL PHENOXY SUBSTITUTED PROPYL DERIVATIVES USEFUL AS D4 ANTAGONISTS
  申请人：Fink M. David

  公开号：US20070004695A1

  公开（公告）日：2007-01-04

  The compounds are of the class thienoisoxazolyl- and thienylpyrrazolyl-phenoxy substituted propyl derivatives, useful as D 4 antagonists. Said compounds are useful for the treatment of medical conditions mediated by inhibition of D 4 receptor. These conditions comprise, for example, Attention Deficit Hyperactivity Disorder, Obsessive-Compulsive Disorder, Psychoses, Substance Abuse, Substance Dependence, Parkinson's Disease, Parkinsonism, Tardive Diskinesia, Gilles de la Tourette Syndrome, Conduct Disorder, and Oppositional Defiant Disorder. A further aspect of the invention is to provide a pharmaceutical composition, intermediates, and a method of making said class of compounds.

  这些化合物属于类别为噻唑异噁唑基和噻吩吡唑基苯氧基取代的丙基衍生物，可用作D4受体拮抗剂。这些化合物可用于治疗通过抑制D4受体介导的医疗状况。这些状况包括例如注意力缺陷多动障碍、强迫症、精神病、物质滥用、物质依赖、帕金森病、帕金森综合症、迟发性运动障碍、吉尔·德·拉·图雷特综合症、行为障碍和反抗行为障碍。发明的另一个方面是提供一种制药组合物、中间体和制备该类化合物的方法。
• 3-(1-Substituted-4-piperazinyl)-1H-indazoles, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0417653A1

  公开（公告）日：1991-03-20

  This invention relates to 3-(1-substituted-4-piperazinyl)-1H-indazoles having the following formula wherein R1 is hydrogen, lower alkyl, arylloweralkyl, acyl, cycloalkylloweralkylene, and phenylsulfonyl; and R2 is hydrogen, lower alkyl, hydroxyloweralkyl of the formula (̵loweralkylene)̵ OH , arylloweralkyl, acyl, cycloalkyl- loweralkylene, where Z is selected from hydrogen, halogen, loweralkoxy, CF3, N02, and NH2; where Z is as defined above; where Z is as defined above; where R3 and R4 are each independently hydrogen and loweralkyl; where Z is as defined above; where R and R are each independently hydrogen and loweralkyl; X is hydrogen, loweralkyl, hydroxyl, halogen, loweralkoxy, CF3, N02 and amino; n is an integer of 1 to 4, with the further proviso that R2 is not loweralkyl when R1 is hydrogen or acyl and X is chloro; the pharmaceutically acceptable acid addition salts thereof and where appropriate the geometric isomers, the stereoisomers and racemic mixers thereof. The compounds of this invention display utility as analgesic and antipsychotic agents.

  本发明涉及具有下式的 3-(1-取代-4-哌嗪基)-1H-吲唑 其中 R1 是氢、低级烷基、芳基低级烷基、酰基、环烷基低级烷基和苯磺酰基；R2 是氢、低级烷基、式 (̵低级烷基)̵OH 的羟基低级烷基、芳基低级烷基、酰基、环烷基低级烷基、 其中 Z 选自氢、卤素、低级烷氧基、CF3、N02 和 NH2； 其中 Z 如上定义 其中 Z 如上定义 其中 R3 和 R4 各自独立地为氢和低级烷基； 其中 Z 如上所定义 其中R和R各自独立地为氢和低级烷基；X为氢、低级烷基、羟基、卤素、低级烷氧基、CF3、N02和氨基；n为1至4的整数，进一步的但书是当R1为氢或酰基和X为氯时，R2不是低级烷基；其药学上可接受的酸加成盐，以及适当时其几何异构体、立体异构体和外消旋混合物。本发明的化合物具有镇痛和抗精神病作用。
• THIENOISOXAZOLYL AND THIENYLPYRRAZOLYL PHENOXY SUBSTITUTED PROPYL DERIVATIVES USEFUL AS D4 ANTAGONISTS
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1216250B1

  公开（公告）日：2003-11-19