5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine
• 英文别名: 7-chloro-3-(2,4-dichlorophenyl)-2,5-dimethylpyrazolo[4,3-b]pyridine
• 化学式: C₁₄H₁₀Cl₃N₃
• 分子量: 326.613
• InChiKey: UHXRWRLELBWKAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine 在 对甲苯磺酸 作用下， 以 二正丙胺 为溶剂， 生成 5-methyl-7-(dipropylamino)-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine
  参考文献：
  名称：

  CRF antagonistic pyrazolo[4,3-b]pyridines

  摘要：

  这项发明涉及公式化合物，包括其立体异构体和药学上可接受的酸盐形式，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烷基硫醚基; R3是Ar1或Het1; R4是氢或C1-6烷基; R5是氢，C1-8烷基，单或双(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯基C1-6烷基，单或双(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，噻吩基甲基，呋喃基甲基，四氢呋喃基甲基，C1-6烷硫醚基C1-6烷基，单或双(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烷基，哌啶基，同戊二氮杂环基，吗啉基或硫代吗啉基，可选择地取代1或2个取代基，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分别是可选择地取代的苯基; Het1是可选择地取代的吡啶基; 具有CRF受体拮抗作用; 包含这种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。

  公开号：

  US06613777B1
• 作为产物：
  描述：

  2,2',4'-三氯苯乙酮 在 2-甲基苯磺酸 、 肼 、 三氯氧磷 作用下， 以 二苯醚 、 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 1.0h， 生成 5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine
  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
• 作为试剂：
  描述：

  5-methyl-7-hydroxy-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine 、 三氯氧磷 在 5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine 作用下， 反应 2.0h， 以yielding 5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine (intermediate 5)的产率得到5-methyl-7-chloro-2-methyl-3-(2,4-dichlorophenyl)pyrazolo[4,3-b]pyridine
  参考文献：
  名称：

  CRF antagonistic pyrazolo[4,3-b]pyridines

  摘要：

  本发明涉及式的化合物，包括其立体异构体和药学上可接受的酸盐形式，其中R1为C1-6烷基，NR5R6，OR6或SR6；R2为C1-6烷基，C1-6烷氧基或C1-6烷硫基；R3为Ar1或Het1；R4为氢或C1-6烷基；R5为氢，C1-8烷基，单或双（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，单或双（C1-6烷基）氨基-C1-6烷基或C1-6烷氧基C1-6烷基；R6为C1-8烷基，单或双（C3-6环烷基）甲基，Ar2C1-6烷基，Ar2oxyC1-6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烷基，哌啶基，同型哌啶基，吗啉基或硫代吗啉基，可选地取代1或2个取代基，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分别为可选的取代苯基；Het1为可选的取代吡啶基；具有CRF受体拮抗作用；含有这种化合物作为活性成分的制药组合物；通过给予式（I）化合物的有效量治疗与CRF的过度分泌相关的疾病，例如抑郁症，焦虑症，物质滥用等的方法。

  公开号：

  US06613777B1

文献信息

• [EN] CRF ANTAGONISTIC PYRAZOLO[4,3-B]PYRIDINES<br/>[FR] PYRAZOLO[4,3-B]PYRIDINES ANTAGONISTES DU FACTEUR DE LIBERATION DE LA CORTICOTROPINE (CRF)
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1999045007A1

  公开（公告）日：1999-09-10

  (EN) This invention concerns compounds of formula (I), including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is C1-6alkyl, NR5R6, OR6 or SR6; R2 is C1-6alkyl, C1-6alkyloxy, or C1-6alkylthio; R3 is Ar1 or Het1; R4 is hydrogen or C1-6alkyl; R5 is hydrogen, C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxyC1-6alkyl, mono- or di(C1-6alkyl)amino-C1-6alkyl or C1-6alkyloxyC1-6alkyl, R6 is C1-8alkyl, mono-or di(C3-6cycloalkyl)methyl, Ar2C1-6alkyl, Ar2oxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, tetrahydrofuranylmethyl, C1-6alkylthioC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, or C1-6alkylcarbonylC1-6alkyl; or R5 and R6 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 C1-6alkyl or C1-6alkyloxyC1-6alkyl; and Ar1 and Ar2 are each optionally substituted phenyl; and Het1 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).(FR) La présente invention concerne des composés de formule (I), y compris les stéréoisomères et leurs sels d'addition acide pharmaceutiquement acceptables, dans laquelle R1 est un C1-6 alkyle, NR5R6, OR6 ou SR6; R2 est un C1-6 alkyle, un C1-6 alkyloxy, ou un C1-6 alkylthio; R3 est un Ar1 ou un Het1; R4 est un hydrogène ou un C1-6 alkyle; R5 est un hydrogène, un C1-8 alkyle, un mono- ou di(C3-6 cycloalkyle)méthyle, un C3-6 cycloalkyle, un C3-6 alcényle, un hydroxyC1-6 alkyle, un C1-6 alkylcarbonyloxyC1-6 alkyle, un mono- ou un di(C1-6 alkyle)aminoC1-6 alkyle ou un C1-6 alkyloxyC1-6 alkyle; R6 est un C1-8 alkyle, un mono- ou un di(C3-6 cycloalkyle)méthyle, un Ar2C1-6 alkyle, un Ar2oxyC1-6 alkyle, un C1-6 alkyloxyC1-6 alkyle, un hydroxyC1-6 alkyle, un C3-6 alcényle, un thiénylméthyle, un furanylméthyle, un tétrahydrofuranylméthyle, un C1-6 alkylthioC1-6 alkyle, un mono- ou di(C1-6 alkyle)aminoC1-6 alkyle, un di(C1-6 alkyle)amino, ou un C1-6 alkylcarbonylC1-6 alkyle; ou R5 et R6 pris ensemble avec l'atome d'azote auquel ils sont liés peuvent former un groupe pyrrolidinyle, pipéridinyle, homopipéridinyle, morpholinyle, ou thiomorpholinyle, éventuellement substitué par 1 ou 2 substituants chacun choisi indépendamment parmi un groupe C1-6 alkyle ou C1-6 alkyloxyC1-6 alkyle; et Ar1 et Ar2 sont chacun un groupe phényle éventuellement substitué; et Het1 est un groupe pyridinyle éventuellement substitué. Tous ces composés possédent des propriétés antagonistes du récepteur de CRF. La présente invention concerne aussi les compositions qui renferment de tels composés comme principes actifs, et les méthodes de soins en rapport avec les troubles d'hypersécrétion de CRF tels que la dépression, l'anxiété, l'abus d'intoxicant, par l'administration d'une quantité efficace d'un composé de formule (I).

  本发明涉及公式(I)的化合物，包括其立体异构体和药学上可接受的酸盐形式，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烷硫基; R3是Ar1或Het1; R4是氢或C1-6烷基; R5是氢，C1-8烷基，单或双(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C1-6烷基，单或双(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，噻吩基甲基，呋喃基甲基，四氢呋喃基甲基，C1-6烷硫基C1-6烷基，单或双(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烷基，哌啶基，同源哌啶基，吗啉基或硫代吗啉基，可选择地用1或2个取代基独立地选择自C1-6烷基或C1-6烷氧基C1-6烷基; Ar1和Ar2分别是可选择取代的苯基; Het1是可选择取代的吡啶基; 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)化合物的有效量治疗与CRF过度分泌相关的疾病，如抑郁症，焦虑症，物质滥用的方法。
• 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.
• CRF antagonistic pyrazolo&lsqb;4,3-b&rsqb;pyridines
  申请人：——

  公开号：US06613777B1

  公开（公告）日：2003-09-02

  This invention concerns compounds of formula including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is C1-6alkyl, NR5R6, OR6 or SR6; R2 is C1-6alkyl, C1-6alkyloxy, or C1-6alkylthio; R3 is Ar1 or Het1; R4 is hydrogen or C1-6alkyl; R5 is hydrogen, C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxyC1-6alkyl, mono- or di(C1-6alkyl)amino-C1-6alkyl or C1-6alkyloxyC1-6alkyl; R6 is C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, Ar2C1-6alkyl, Ar2oxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, tetrahydrofuranylmethyl, C1-6alkylthioC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, or C1-6alkylcarbonylC1-6alkyl; or R5 and R6 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 C1-6alkyl or C1-6alkyloxyC1-6alkyl; and and Ar1 and Ar2 are each optionally substituted phenyl; and Het1 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).

  本发明涉及式的化合物，包括其立体异构体和药学上可接受的酸盐形式，其中R1为C1-6烷基，NR5R6，OR6或SR6；R2为C1-6烷基，C1-6烷氧基或C1-6烷硫基；R3为Ar1或Het1；R4为氢或C1-6烷基；R5为氢，C1-8烷基，单或双（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，单或双（C1-6烷基）氨基-C1-6烷基或C1-6烷氧基C1-6烷基；R6为C1-8烷基，单或双（C3-6环烷基）甲基，Ar2C1-6烷基，Ar2oxyC1-6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烷基，哌啶基，同型哌啶基，吗啉基或硫代吗啉基，可选地取代1或2个取代基，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分别为可选的取代苯基；Het1为可选的取代吡啶基；具有CRF受体拮抗作用；含有这种化合物作为活性成分的制药组合物；通过给予式（I）化合物的有效量治疗与CRF的过度分泌相关的疾病，例如抑郁症，焦虑症，物质滥用等的方法。