1-甲基-4-氨基-3-(2,4-二氯苯基)吡唑 | 1025833-98-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-甲基-4-氨基-3-(2,4-二氯苯基)吡唑
• 英文名称: 1-methyl-4-amino-3-(2,4-dichlorophenyl)pyrazole
• 英文别名: 3-(2,4-Dichlorophenyl)-1-methylpyrazol-4-amine
• CAS: 1025833-98-0
• 化学式: C₁₀H₉Cl₂N₃
• 分子量: 242.108
• InChiKey: FSZFOHMIIMFIHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-甲基-4-氨基-3-(2,4-二氯苯基)吡唑 以 二苯醚 、 苯 为溶剂， 生成 5-methyl-7-chloro-1-methyl-3-(2,4-dichlorophenyl)-pyrazolo[4,3-b]pyridine
  参考文献：
  名称：

  通过4-邻苯二甲酰亚胺基-3-苯基吡唑的甲基化合成1-甲基-3-苯基吡唑并[4,3-b]吡啶，并向高效促肾上腺皮质激素释放因子1型拮抗剂进行优化。

  摘要：

  通过1-甲基-4-氨基-3-苯基吡唑8与乙酰乙酸乙酯的环化反应合成了1-甲基-3-苯基吡唑并[4，3-b]吡啶。该系列化合物的优化产生具有亚纳摩尔结合亲和力的CRF（1）拮抗剂。还发现带有极性基团如甲氧基或羟基的化合物非常活泼。

  DOI：

  10.1016/s0960-894x(03)00622-x
• 作为产物：
  描述：

  2,2',4'-三氯苯乙酮 在 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1-甲基-4-氨基-3-(2,4-二氯苯基)吡唑
  参考文献：
  名称：

  Synthesis of 3-phenylpyrazolo[4,3-b]pyridines via a convenient synthesis of 4-amino-3-arylpyrazoles and SAR of corticotropin-Releasing factor receptor type-1 antagonists

  摘要：

  3-Phenylpyrazolo[4,3-b]pyridines were synthesized via a cyclization of 4-amino-3-phenylpyrazoles 11-13 with ethyl acetoacetate. These compounds were found to be potent CRF1 antagonists. The 2-alkylpyrazolo[4,3-b]pyridines were more polar but less active than the corresponding 1-alkyl-isomers. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00621-8

文献信息

• Synthesis of 1-methyl-3-phenylpyrazolo[4,3-b]pyridines via a methylation of 4-phthalimino-3-phenylpyrazoles and optimization toward highly potent corticotropin-releasing factor type-1 antagonists
  作者：Charles Q. Huang、Keith Wilcoxen、James R. McCarthy、Mustaph Haddach、Dimitri Grigoriadis、Chen Chen

  DOI：10.1016/s0960-894x(03)00622-x

  日期：2003.10

  1-Methyl-3-phenylpyrazolo[4,3-b]pyridines were synthesized via a cyclization reaction of 1-methyl-4-amino-3-phenylpyrazoles 8 with ethyl acetoacetate. Optimization of this series of compounds resulted in CRF(1) antagonists with subnanomolar binding affinity. Compounds bearing a polar group such as methoxy or hydroxy were also found to be very active.

  通过1-甲基-4-氨基-3-苯基吡唑8与乙酰乙酸乙酯的环化反应合成了1-甲基-3-苯基吡唑并[4，3-b]吡啶。该系列化合物的优化产生具有亚纳摩尔结合亲和力的CRF（1）拮抗剂。还发现带有极性基团如甲氧基或羟基的化合物非常活泼。
• CRF antagonistic pyrazolo[4,3-b]pyridines
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20040121999A1

  公开（公告）日：2004-06-24

  This invention concerns compounds of formula 1 including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R 1 is C 1-6 alkyl, NR 5 R 6 , OR 6 or SR 6 ; R 2 is C 1-6 alkyl, C 1-6 alkyloxy, or C 1-6 alkylthio; R 3 is Ar 1 or Het 1 ; R 4 is hydrogen or C 1-6 alkyl; R 5 is hydrogen, C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxyC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; R 6 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, Ar 2 C 1-6 alkyl, Ar 2 oxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 alkenyl, thienylmethyl, furanylmethyl, tetrahydrofuranylmethyl, C 1-6 alkylthioC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, or C 1-6 alkylcarbonylC 1-6 alkyl; or R 5 and R 6 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl, morpholinyl, or thiomorpholinyl group, optionally substituted with 1 or 2 substituents each independently selected from C 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; and and Ar 1 and Ar 2 are each optionally substituted phenyl; and Het 1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及公式1的化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是C1-6烷基，NR5R6，OR6或SR6; R2是C1-6烷基，C1-6烷氧基或C1-6烷基硫基; R3是Ar1或Het1; R4是氢或C1-6烷基; R5是氢，C1-8烷基，单个或双(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯氧基C1-6烷基，单个或双(C1-6烷基)氨基C1-6烷基或C1-6烷氧基C1-6烷基; R6是C1-8烷基，单个或双(C3-6环烷基)甲基，Ar2C1-6烷基，Ar2氧基C1-6烷基，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩甲基，呋喃甲基，四氢呋喃甲基，C1-6烷硫基C1-6烷基，单个或双(C1-6烷基)氨基C1-6烷基，双(C1-6烷基)氨基或C1-6烷基羧酰基C1-6烷基; 或R5和R6与它们连接的氮原子一起可以形成吡咯啉基，哌啶基，同型哌啶基，吗啉基或硫代吗啉基，可选择地被1或2个取代基取代，每个取代基独立选择自C1-6烷基或C1-6烷氧基C1-6烷基; Ar1和Ar2均为可选取代的苯基; Het1为可选取代的吡啶基; 具有CRF受体拮抗性质; 包含此类化合物作为活性成分的药物组合物; 通过给予公式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，如抑郁症，焦虑症，物质滥用等的方法。
• US6613777B1
  申请人：——

  公开号：US6613777B1

  公开（公告）日：2003-09-02
• Synthesis of 3-phenylpyrazolo[4,3-b]pyridines via a convenient synthesis of 4-amino-3-arylpyrazoles and SAR of corticotropin-Releasing factor receptor type-1 antagonists
  作者：Keith Wilcoxen、Charles Q Huang、James R McCarthy、Dimitri E Grigoriadis、Chen Chen

  DOI：10.1016/s0960-894x(03)00621-8

  日期：2003.10

  3-Phenylpyrazolo[4,3-b]pyridines were synthesized via a cyclization of 4-amino-3-phenylpyrazoles 11-13 with ethyl acetoacetate. These compounds were found to be potent CRF1 antagonists. The 2-alkylpyrazolo[4,3-b]pyridines were more polar but less active than the corresponding 1-alkyl-isomers. (C) 2003 Elsevier Ltd. All rights reserved.