5-chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine | 942948-56-3

• 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-chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine
• 英文别名: 5-chloro-4-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-3-nitropyridin-2-amine
• CAS: 942948-56-3
• 化学式: C₁₆H₁₇Cl₂N₅O₂
• 分子量: 382.249
• InChiKey: PFOWBOCPGMCSJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  91.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine 在 sodium dithionite 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  [EN] SALTS AND POLYMORPHIC FORMS OF 6-CHLORO-7-(4-(4-CHLOROBENZYL)PIPERAZIN-1-YL)-2-(1,3-DIMETHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDINE
  [FR] SELS ET FORMES POLYMORPHES DE 6-CHLORO-7-(4-(4-CHLOROBENZYL)PIPÉRAZIN-1-YL)-2-(1,3-DIMÉTHYL-1H-PYRAZOL-4-YL)-3H-IMIDAZO[4,5-B]PYRIDINE

  摘要：

  本发明涉及化合物A（6-氯-7-（4-（4-氯苯甲基）哌嗪-1-基）-2-（1,3-二甲基-1H-吡唑-4-基）-3H-咪唑[4,5-b]吡啶）的盐和多晶形，该化合物是Aurora激酶和类FMS酪氨酸激酶3（FLT3）活性的抑制剂。本发明还涉及制备该化合物的盐和多晶形的过程，以及包含它们的制药组合物，并将它们用于治疗增殖性疾病，如癌症，以及其他与Aurora激酶和/或FLT3活性有关的疾病或病况。

  公开号：

  WO2021176216A1
• 作为产物：
  描述：

  2-氨基-4-氯吡啶 在 N-氯代丁二酰亚胺 、 硫酸 、 硝酸 、 N,N-二异丙基乙胺 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 20.17h， 生成 5-chloro-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine
  参考文献：
  名称：

  咪唑并[4,5-b]吡啶类激酶抑制剂的优化：鉴定双 FLT3/Aurora 激酶抑制剂作为治疗急性髓系白血病的口服生物可利用临床前开发候选药物

  摘要：

  对基于咪唑并[4,5 - b ]吡啶的系列极光激酶抑制剂进行优化，鉴定出 6-chloro-7-(4-(4-chlorobenzyl)pirazin-1-yl)-2-(1, 3-dimethyl-1 H -pyrazol-4-yl)-3 H -imidazo[4,5- b ]pyridine ( 27e )，一种强效的 Aurora 激酶抑制剂 (Aurora-A K d = 7.5 nM, Aurora-B K d = 48 nM)、FLT3 激酶 ( K d = 6.2 nM) 和 FLT3 突变体，包括 FLT3-ITD ( K d = 38 nM) 和 FLT3(D835Y) ( K d = 14 nM)。FLT3-ITD 引起组成型 FLT3 激酶激活，在 20-35% 的成人和 15% 的急性髓性白血病 (AML) 患儿中检测到，这两个年龄组的预后都很差。在体内环境中，27e在口服给药后强烈抑制FLT3

  DOI：

  10.1021/jm300952s

文献信息

• Enzyme Inhibitors
  申请人：Bavetsias Vassilios

  公开号：US20090247507A1

  公开（公告）日：2009-10-01

  Compounds of formula (I), are aurora kinase inhibitors: wherein X is —N—, —CH2—N—, —CH2—CH—, or —CH—; R1 is a radical of formula (IA) wherein Z is —CH2—, —NH—, -0-, —S(O)— —S—, —S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, —CN, —CF3, —OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z&It;1> is —S—, —S(O)—, —S(O)2—, —O—, —SO2NH—, —NHSO2—, NHC(═O)NH, —NH(C═S)NH—, Or —N(R4)—wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk&It;1> and Alk&It;2> are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently 0 or 1. Data supplied from the esp@cenet datatbase—Worldwide d77

  式(I)的化合物是极光激酶抑制剂：其中X是—N—、—CH2—N—、—CH2—CH—或—CH—；R1是式(IA)的基团，其中Z是—CH2—、—NH—、-O-、—S(O)—、—S—、—S(O)2或具有3-7个环原子的二价单环碳环或杂环基团；Alk是任选取代的二价C1-C6亚烷基基团；A是氢或任选取代的具有5-7个环原子的单环碳环或杂环环；r、s和t独立地为0或1，前提是当A为氢时，至少一个r和s为1；R2是卤素、—CN、—CF3、—OCH3或环丙基；R3是式(IB)的基团，其中Q是氢或任选取代的苯基或具有5或6个环原子的单环杂环环；Z<1>是—S—、—S(O)—、—S(O)2—、—O—、—SO2NH—、—NHSO2—、NHC(═O)NH、—NH(C═S)NH—或—N(R4)—，其中R4是氢、C1-C3烷基、环烷基或苄基；Alk<1>和Alk<2>独立地是任选取代的二价C1-C3亚烷基基团；m、n和p独立地为0或1。数据来自esp@cenet数据库—Worldwide d77。
• [EN] PHARMACEUTICALLY ACTIVE COMPOUNDS<br/>[FR] COMPOSÉS PHARMACEUTIQUEMENT ACTIFS
  申请人：CANCER REC TECH LTD

  公开号：WO2013190319A1

  公开（公告）日：2013-12-27

  The present invention relates to compounds of formula I: wherein R1 and R2 are as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated.

  本发明涉及式I的化合物：其中R1和R2如本文所定义，或其药学上可接受的盐或溶剂。式I的化合物是极化酪氨酸激酶和/或FLT3的抑制剂。本发明还涉及制备这些化合物的过程，包括它们的制药组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及极化酪氨酸激酶和/或FLT3活性的疾病或病况中的使用。
• Enzyme inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US08088761B2

  公开（公告）日：2012-01-03

  Compounds of formula (I), are aurora kinase inhibitors: wherein X is —N—, —CH2-N—, —CH2-CH—, or —CH—; R1 is a radical of formula (IA) wherein Z is —CH2-, —NH—, -0-, —S(O)— —S—, —S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, —CN, —CF3, —OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z&It;1> is —S—, —S(O)—, —S(O)2-, —O—, —SO2NH—, —NHSO2-, NHC(═O)NH, —NH(C═S)NH—, Or —N(R4)— wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk&It;1> and Alk&It;2> are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently 0 or 1.

  式（I）的化合物是极光激酶抑制剂：其中X是- N-，- CH2-N-，- CH2-CH-或- CH-；R1是式（IA）的基团，其中Z是- CH2-，- NH-，- 0-，- S（O）-，- S-，- S（O）2或具有3-7个环原子的二价单环芳环或杂环基团；Alk是可选取代的二价C1-C6烷基链基团；A是氢或具有5-7个环原子的可选取代的单环芳环或杂环；r，s和t独立地为0或1，前提是当A为氢时，至少有一个r和s为1；R2是卤素，- CN，- CF3，- OCH3或环丙基；R3是式（IB）的基团，其中Q是氢或可选取代的具有5或6个环原子的苯基或单环杂环；Z1是- S-，- S（O）-，- S（O）2-，- O-，- SO2NH-，- NHSO2-，NHC（=O）NH，- NH（C= S）NH-或- N（R4）-，其中R4是氢，C1-C3烷基，环烷基或苯甲基；Alk1和Alk2是独立的可选取代的二价C1-C3烷基链基团；m，n和p独立地为0或1。
• PHARMACEUTICALLY ACTIVE COMPOUNDS
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US20150266868A1

  公开（公告）日：2015-09-24

  The present invention relates to compounds of formula I: wherein R 1 and R 2 are as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated.

  本发明涉及公式I的化合物：其中R1和R2如本文所定义，或其药学上可接受的盐或溶剂。公式I的化合物是aurora激酶和/或FLT3的抑制剂。本发明还涉及制备这些化合物的方法，包括它们的制药组合物，以及它们在治疗增殖性疾病，如癌症，以及其他涉及aurora激酶和/或FLT3活性的疾病或病况中的使用。
• Pharmaceutically active compounds
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US09447092B2

  公开（公告）日：2016-09-20

  The present invention relates to compounds of formula I: wherein R1 and R2 are as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated.

  本发明涉及公式I的化合物：其中R1和R2如本文所定义，或其药学上可接受的盐或溶剂。公式I的化合物是aurora激酶和/或FLT3的抑制剂。本发明还涉及制备这些化合物的过程，包括它们的制药组合物以及它们在治疗增生性疾病（如癌症）以及其他涉及aurora激酶和/或FLT3活性的疾病或情况中的应用。