ethyl 3-(2-amino-4-fluoroanilino)-1-methylpyrazole-4-carboxylate | 79305-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(2-amino-4-fluoroanilino)-1-methylpyrazole-4-carboxylate
• CAS: 79305-68-3
• 化学式: C₁₃H₁₅FN₄O₂
• 分子量: 278.286
• InChiKey: QFANGVVMUQUUAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.06
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  82.17
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(2-amino-4-fluoroanilino)-1-methylpyrazole-4-carboxylate 在 四氯化钛 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.5h， 生成 4-(7-fluoro-2,10-dihydro-2-methylpyrazolo<3,4-b><1,5>benzodiazepin-4-yl)-1-methylpiperazine 1-oxide
  参考文献：
  名称：

  一系列4-哌嗪基吡唑并[3,4-b]-和-[4,3-b] [1,5]苯二氮杂类化合物的合成和药理学评价。

  摘要：

  描述了一系列吡唑并[b] [1,5]苯并二氮杂s的合成和药理学评价。在大鼠的三部分操作性抗冲突试验中，一些4-哌嗪基-2,10-二氢吡唑并[3,4-b] [1,5]苯并二氮杂卓衍生物具有较强的抗焦虑活性。化合物21和30在释放冲突抑制行为方面比临床上有效的抗焦虑药氯氮卓更具活性。这项研究表明，分别在噻吩和二苯并二氮杂卓衍生物氟美沙平和氯氮平中发现的抗焦虑和抗多巴胺能活性已解离。描述并评估了其他三个其他二氢吡唑并[b] [1,5]苯并二氮杂ring环系统的实例，发现它们的活性较低。

  DOI：

  10.1021/jm00132a012
• 作为产物：
  描述：

  3-氨基-1-甲基-吡唑-4-羧酸乙酯 在 palladium on activated charcoal 正丁基锂 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， -15.0~25.0 ℃ 、413.69 kPa 条件下， 反应 1.17h， 生成 ethyl 3-(2-amino-4-fluoroanilino)-1-methylpyrazole-4-carboxylate
  参考文献：
  名称：

  一系列4-哌嗪基吡唑并[3,4-b]-和-[4,3-b] [1,5]苯二氮杂类化合物的合成和药理学评价。

  摘要：

  描述了一系列吡唑并[b] [1,5]苯并二氮杂s的合成和药理学评价。在大鼠的三部分操作性抗冲突试验中，一些4-哌嗪基-2,10-二氢吡唑并[3,4-b] [1,5]苯并二氮杂卓衍生物具有较强的抗焦虑活性。化合物21和30在释放冲突抑制行为方面比临床上有效的抗焦虑药氯氮卓更具活性。这项研究表明，分别在噻吩和二苯并二氮杂卓衍生物氟美沙平和氯氮平中发现的抗焦虑和抗多巴胺能活性已解离。描述并评估了其他三个其他二氢吡唑并[b] [1,5]苯并二氮杂ring环系统的实例，发现它们的活性较低。

  DOI：

  10.1021/jm00132a012

文献信息

• Pyrazolo [3,4-b][1,5]benzodiazepine compounds
  申请人：Lilly Industries Limited

  公开号：US04404137A1

  公开（公告）日：1983-09-13

  Compounds are described of the formula ##STR1## or an acid addition salt thereof; in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, halogen, C.sub.1-4 haloalkyl, C.sub.1-4 alkanoyl, nitro, amino, C.sub.2-4 acylamino, cyano, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkoxy or a group of the formula --SO.sub.2 N(R.sup.8).sub.2, --SO.sub.2 R.sup.8 or --SO.sub.3 R.sup.8 where R.sup.8 is C.sub.1-4 alkyl, C.sub.1-4 haloalkyl or optionally substituted phenyl; in which R.sup.5 is a group of the formula ##STR2## where R.sup.9 is hydrogen, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkenyl, C.sub.1-4 alkanoyl, benzyl, cyano or optionally substituted phenyl, where R.sup.10 is hydrogen, C.sub.1-4 alkyl or optionally substituted phenyl and where n is 0 or 1; in which R.sup.6 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, benzyl, C.sub.1-6 alkanoyl, C.sub.1-4 carbalkoxy or benzoyl; and in which R.sup.7 is one of the values of R.sup.6 or halogen, nitro, cyano, amino or C.sub.1-4 acylamino. The compounds are active as pharmaceuticals and particularly in the treatment of disorders of the central nervous system. Intermediate compounds in which R.sup.5 is thiol, hydroxy, or amino are also described.

  描述了化合物的公式为##STR1##或其酸盐；其中R.sup.1、R.sup.2、R.sup.3和R.sup.4分别代表氢、C.sub.1-4烷基、C.sub.2-4烯基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、卤素、C.sub.1-4卤代烷基、C.sub.1-4烷酰基、硝基、氨基、C.sub.2-4酰胺基、氰基、羟基、C.sub.1-4烷氧基、C.sub.1-4烷硫基、C.sub.1-4卤代烷氧基或具有公式--SO.sub.2N(R.sup.8).sub.2、--SO.sub.2R.sup.8或--SO.sub.3R.sup.8的基团，其中R.sup.8是C.sub.1-4烷基、C.sub.1-4卤代烷基或可选择取代的苯基；其中R.sup.5是具有公式##STR2##的基团，其中R.sup.9是氢、C.sub.1-4烷基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、C.sub.1-4卤代烷基、C.sub.2-4烯基、C.sub.1-4烷酰基、苄基、氰基或可选择取代的苯基，其中R.sup.10是氢、C.sub.1-4烷基或可选择取代的苯基，n为0或1；其中R.sup.6是氢、C.sub.1-10烷基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、C.sub.1-4卤代烷基、苄基、C.sub.1-6烷酰基、C.sub.1-4羧基烷氧基或苯甲酰基；其中R.sup.7是R.sup.6或卤素、硝基、氰基、氨基或C.sub.1-4酰胺基的值之一。这些化合物在药物中具有活性，特别用于治疗中枢神经系统疾病。还描述了其中间体化合物，其中R.sup.5是硫醇、羟基或氨基。
• 4-Substituted-1-(3-[2-aminoanilino]-1-pyrazole-4-carbonyl)piperazine
  申请人：Lilly Industries Limited

  公开号：US04486591A1

  公开（公告）日：1984-12-04

  Compounds are described of the formula ##STR1## or an acid addition salt thereof; in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, halogen, C.sub.1-4 haloalkyl, C.sub.1-4 alkanoyl, nitro, amino, C.sub.2-4 acylamino, cyano, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkoxy or a group of the formula -SO.sub.2 N(R.sup.8).sub.2, -SO.sub.2 R.sup.8 or -SO.sub.3 R.sup.8 where R.sup.8 is C.sub.1-4 alkyl, C.sub.1-4 haloalkyl or optionally substituted phenyl; in which R.sup.5 is a group of the formula ##STR2## where R.sup.9 is hydrogen, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkenyl, C.sub.1-4 alkanoyl, benzyl, cyano or optionally substituted phenyl, where R.sup.10 is hydrogen, C.sub.1-4 alkyl or optionally substituted phenyl and where n is 0 or 1; in which R.sup.6 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, benzyl, C.sub.1-6 alkanoyl, C.sub.1-4 carbalkoxy or benzoyl; and in which R.sup.7 is one of the values of R.sup.6 or halogen, nitro, cyano, amino or C.sub.1-4 acylamino. The compounds are active as pharmaceuticals and particularly in the treatment of disorders of the central nervous system.

  该文描述的是公式## STR1##或其酸加成盐的化合物；其中，R1、R2、R3和R4独立地表示氢、C1-4烷基、C2-4烯基、C3-7环烷基、C3-7环烷基C1-4烷基、卤素、C1-4卤代烷基、C1-4酰基、硝基、氨基、C2-4酰胺基、氰基、羟基、C1-4烷氧基、C1-4烷硫基、C1-4卤代烷氧基或式-SO2N（R8）2、-SO2R8或-SO3R8的基团，其中R8是C1-4烷基、C1-4卤代烷基或可选择取代的苯基；其中R5是式## STR2##的基团，其中R9是氢、C1-4烷基、C3-7环烷基、C3-7环烷基C1-4烷基、C1-4卤代烷基、C2-4烯基、C1-4酰基、苄基、氰基或可选择取代的苯基，其中R10是氢、C1-4烷基或可选择取代的苯基，n为0或1；其中R6为氢、C1-10烷基、C3-7环烷基、C3-7环烷基C1-4烷基、C1-4卤代烷基、苄基、C1-6酰基、C1-4羧基烷氧基或苯甲酰基；而R7是R6的一种值或卤素、硝基、氰基、氨基或C1-4酰胺基。这些化合物在药物中具有活性，特别是在治疗中枢神经系统疾病方面。
• Substituted diazolo[b][1,5]benzodiazepines and their use as CNS agents
  申请人：Lilly Industries Limited

  公开号：US04542131A1

  公开（公告）日：1985-09-17

  Compounds are described of the formula ##STR1## or an acid addition salt thereof; in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, halogen, C.sub.1-4 haloalkyl, C.sub.1-4 alkanoyl, nitro, amino, C.sub.2-4 acylamino, cyano, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkoxy or a group of the formula --SO.sub.2 N(R.sup.8).sub.2, --SO.sub.2 R.sup.8 or --SO.sub.3 R.sup.8 where R.sup.8 is C.sub.1-4 alkyl, C.sub.1-4 haloalkyl or optionally substituted phenyl; in which R.sup.5 is a group of the formula ##STR2## where R.sup.9 is hydrogen, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkenyl, C.sub.1-4 alkanoyl, benzyl, cyano or optionally substituted phenyl, where R.sup.10 is hydrogen, C.sub.1-4 alkyl or optionally substituted phenyl and where n is 0 or 1; in which R.sup.6 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl. C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, benzyl, C.sub.1-6 alkanoyl, C.sub.1-4 carbalkoxy or benzoyl; and in which R.sup.7 is one of the values of R.sup.6 or halogen, nitro, cyano, amino or C.sub.1-4 acylamino. The compounds are active as pharmaceuticals and particularly in the treatment of disorders of the central nervous system.

  该化合物的公式为##STR1##或其酸加成盐;其中R.sup.1、R.sup.2、R.sup.3和R.sup.4独立地表示氢、C.sub.1-4烷基、C.sub.2-4烯基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、卤素、C.sub.1-4卤代烷基、C.sub.1-4酰基、硝基、氨基、C.sub.2-4酰胺基、氰基、羟基、C.sub.1-4烷氧基、C.sub.1-4烷硫基、C.sub.1-4卤代烷氧基或式--SO.sub.2N(R.sup.8).sub.2、--SO.sub.2R.sup.8或--SO.sub.3R.sup.8的基团，其中R.sup.8是C.sub.1-4烷基、C.sub.1-4卤代烷基或可选取代的苯基;其中R.sup.5是式##STR2##的基团，其中R.sup.9是氢、C.sub.1-4烷基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、C.sub.1-4卤代烷基、C.sub.2-4烯基、C.sub.1-4酰基、苄基、氰基或可选取代的苯基，其中R.sup.10是氢、C.sub.1-4烷基或可选取代的苯基，n为0或1;其中R.sup.6是氢、C.sub.1-10烷基、C.sub.3-7环烷基、C.sub.3-7环烷基C.sub.1-4烷基、C.sub.1-4卤代烷基、苄基、C.sub.1-6酰基、C.sub.1-4羧基烷氧基或苯甲酰基;其中R.sup.7是R.sup.6的一个值或卤素、硝基、氰基、氨基或C.sub.1-4酰胺基。这些化合物在药物学中具有活性，特别适用于治疗中枢神经系统疾病。
• Novel benzodiazepine compounds, their preparation, intermediates employed in their preparation, and pharmaceutical compositions containing them
  申请人：Lilly Industries Limited

  公开号：EP0027390A1

  公开（公告）日：1981-04-22

  Compounds are described of the formula or an acid addition salt thereof; in which R', R2, R3 and R' independently represent hydrogen, Ci-4 alkyl, C2-4 alkenyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-4 alkyl, halogen, C1-4 haloalkyl, Ci-4 alkanoyl, nitro, amino, C2-4 acylamino, cyano, hydroxyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 haloalkoxy or a group of the formula -SO2N(R8)2, -SO2R8 or -SO3R8 where R8 is C1-4 alkyl, C1-4 haloalkyl or optionally substituted phenyl; in which R' is a group of theformula where R9 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl Ci-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C1-4 alkanoyl, benzyl, cyano or optionally substituted phenyl, where R10 is hydrogen, C1-4 alkyl or optionally substituted phenyl and where n is 0 or 1; in which R6 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl. C3-7 cycloalkyl C1-4 alkyl, C1-4 haloalkyl, benzyl, Ci-6 alkanoyl, C1-4 carbalkoxy or benzoyl; and in which R' is one of the values of R6 or halogen, nitro, cyano, amino or C1-4 acylamino. The compounds are active as pharmaceuticals and particularly in the treatment of disorders of the central nervous system.

  所述化合物的化学式为 或其酸加成盐；其中 R'、R2、R3 和 R'独立地代表氢、Ci-4 烷基、C2-4 烯基、C3-7 环烷基、C3-7 环烷基 C1-4 烷基、卤素、C1-4 卤代烷基、Ci-4 烷酰基、硝基、氨基、C2-4 乙酰氨基、氰基、羟基、C1-4 烷氧基、C1-4 烷硫基、C1-4 卤代烷氧基或式 -4- 烷氧基的基团、氰基、羟基、C1-4 烷氧基、C1-4 烷硫基、C1-4 卤代烷氧基或式 -SO2N(R8)2、-SO2R8 或 -SO3R8 的基团，其中 R8 为 C1-4 烷基、C1-4 卤代烷基或任选取代的苯基；其中 R' 是式中的一个基团 其中 R9 是氢、C1-4 烷基、C3-7 环烷基、C3-7 环烷基 Ci-4烷基、C1-4卤代烷基、C2-4烯基、C1-4烷酰基、苄基、氰基或任选取代的苯基，其中 R10 是氢、C1-4 烷基或任选取代的苯基，n 是 0 或 1；其中 R6 是氢、C1-10 烷基、C3-7 环烷基、C3-7 环烷基 Ci-4烷基、C1-4卤代烷基、C2-4烯基、C1-4烷酰基、苄基、氰基或任选取代的苯基。C3-7环烷基 C1-4烷基、C1-4卤代烷基、苄基、Ci-6烷酰基、C1-4碳烷氧基或苯甲酰基；其中R'是R6的值之一或卤素、硝基、氰基、氨基或C1-4酰氨基。这些化合物具有药物活性，特别是在治疗中枢神经系统疾病方面。
• CHAKRABARTI, JIBAN K.;HOTTEN, TERRENCE M.;PULLAR, IAN A.;TYE, NICHOLAS C., J. MED. CHEM., 32,(1989) N2, C. 2573-2582
  作者：CHAKRABARTI, JIBAN K.、HOTTEN, TERRENCE M.、PULLAR, IAN A.、TYE, NICHOLAS C.

  DOI：——

  日期：——