3-甲基-1-(5-硝基吡啶-2-基)哌嗪 | 773879-30-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 3-甲基-1-(5-硝基吡啶-2-基)哌嗪
• 英文名称: 3-methyl-1-(5-nitropyridin-2-yl)piperazine
• CAS: 773879-30-4
• 化学式: C₁₀H₁₄N₄O₂
• 分子量: 222.247
• InChiKey: XYMPRRMVLJQEAW-UHFFFAOYSA-N

物化性质

• 熔点：
  107-109

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-甲基-1-(5-硝基吡啶-2-基)哌嗪 在 盐酸 、 铁粉 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 27.0h， 生成  N-(2-((5-chloro-2-((6-(3-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

  摘要：

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

  DOI：

  10.1016/j.bioorg.2018.09.019
• 作为产物：
  描述：

  2-氯-5-硝基吡啶 、 2-甲基哌嗪 在 potassium carbonate 作用下， 以 N-甲基乙酰胺 、 水 为溶剂， 生成 3-甲基-1-(5-硝基吡啶-2-基)哌嗪
  参考文献：
  名称：

  N-[(Piperazinyl)hetaryl]arylsulfonamide compounds

  摘要：

  该发明涉及一般式I的N-[(哌嗪基)杂环基]芳基磺酰胺化合物，其中 Q是双价的、具有1或2个N原子作为环成员的6元杂芳基基团，可选地携带一个或两个取代基R a，该取代基R a独立地从卤素、CN、NO 2、CO 2R 4、COR 5、C 1 -C 4 -烷基和C 1 -C 4 -卤代烷基中选择； Ar是苯基或双价的、具有1或2个N原子作为环成员的6元杂芳基基团，可选地携带一个或两个取代基R b，该取代基R b从卤素、NO 2、CN、CO 2R 4、COR 5、C 1 -C 6 -烷基、C 2 -C 6 -烯基、C 2 -C 6 -炔基、C 3 -C 6 -环烷基、C 3 -C 6 -环烷基-C 1 -C 4 -烷基和C 1 -C 4 -卤代烷基中选择，其中还可能存在两个与Ar相邻的C原子结合的R b基团共同为C 3 -C 4 -亚烷基； R 1 为氢、C 1 -C 4 -烷基、C 1 -C 4 -卤代烷基、C 3 -C 6 -环烷基、C 3 -C 6 -环烷基-C 1 -C 4 -烷基、C 1 -C 4 -羟基烷基、C 1 -C 4 -烷氧基-C 1 -C 4 -烷基、C 3 -C 4 -烯基或C 3 -C 4 -炔基； 其中基团n、R 1 、R 2 、R 3 、R 4 和R 5 具有专利要求中给出的含义，以及这些化合物的N-氧化物和生理上可耐受的酸盐，以及包括至少一种根据权利要求1至10中的任一项所述的N-[(哌嗪基)杂环基]芳基磺酰胺化合物和/或I的至少一种生理上可耐受的酸盐和/或I的N-氧化物的药物组合物，适当地与生理上可接受的载体和/或辅助物质一起用于治疗对多巴胺D 3 受体拮抗剂或激动剂影响有反应的疾病，特别用于治疗中枢神经系统疾病和肾功能障碍。

  公开号：

  US20040204422A1
• 作为试剂：
  描述：

  potassium carbonate 、 2-氯-5-硝基吡啶 、 2-甲基哌嗪 在 ice 、 乙醚 、 Sodium sulfate-III 、 3-甲基-1-(5-硝基吡啶-2-基)哌嗪 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 3-甲基-1-(5-硝基吡啶-2-基)哌嗪
  参考文献：
  名称：

  N-[(piperazinyl)hetaryl]arylsulfonamide compounds

  摘要：

  本发明涉及一般式I中的N-[(哌嗪基)杂芳基]芳基磺酰胺化合物，其中Q是双价的6元杂芳基基团，其作为环成员具有1或2个N原子，可选地携带一个或两个取代基Ra，该取代基独立地从卤素，CN，NO2，CO2R4，COR5，C1-C4烷基和C1-C4卤代烷基中选择；Ar是苯基或6元杂芳基基团，其作为环成员具有1或2个N原子，可选地携带一个或两个取代基Rb，该取代基从卤素，NO2，CN，CO2R4，COR5，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基和C1-C4卤代烷基中选择，还可以两个结合到Ar相邻的C原子的Rb基团一起形成C3-C4烷基；R1是氢，C1-C4烷基，C1-C4卤代烷基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基，C1-C4羟基烷基，C1-C4烷氧基-C1-C4烷基，C3-C4烯基或C3-C4炔基；其中，n，R1，R2，R3，R4和R5基团的含义如专利权要求所述，以及这些化合物的N-氧化物和生理上耐受的酸加成盐，以及包括至少一种N-[(哌嗪基)杂芳基]芳基磺酰胺化合物和/或至少一种I的生理上耐受的酸加成盐和/或I的N-氧化物的制药组合物，适用于治疗对多巴胺D3受体拮抗剂或激动剂影响有反应的疾病，特别是用于治疗中枢神经系统疾病和肾功能障碍。

  公开号：

  US07320979B2

文献信息

• N-[(piperazinyl)hetary]arylsulfonamide compounds with affinity for the dopamine d3 receptor
  申请人：Braje Wilfried

  公开号：US20070054918A1

  公开（公告）日：2007-03-08

  The invention relates to N-[(piperazinyl)hetaryl]arylsulfonamide compounds of the general formula (I) in which Q is a bivalent, 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R a which is/are selected, independently of each other, from halogen, CN, NO 2 , CO 2 R 4 , COR 5 , C 1 —C 4 -alkyl and C 1 —C 4 -haloalkyl; Ar is phenyl or a 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R b , which is/are selected from halogen, NO 2 , CN, CO 2 R 4 , COR 5 , C 1 —C 6 -alkyl, C 2 —C 6 -alkenyl, C 2 —C 6 -alkynyl, C 3 —C 6 -cycloalkyl, C 3 —C 6 -cycloalkyl-C 1 —C 4 -alkyl and C 1 —C 4 -haloalkyl, with it also being possible for two radicals R b which are bonded to adjacent C atoms of Ar to be together C 3 —C 4 -alkylene; R 1 is hydrogen, C 1 —C 4 -alkyl, C 1 —C 4 -haloalkyl, C 3 —C 6 -cycloalkyl, C 3 —C 6 -cycloalkyl-C 1 —C 4 -alkyl, C 1 —C 4 -hydroxyalkyl, C 1 —C 4 -alkoxy-C 1 —C 4 -alkyl, C 3 —C 4 -alkenyl or C 3 —C 4 -alkynyl; with the radicals n, R 1 , R 2 , R 3 , R 4 and R 5 having the meanings given in the patent claims, to the N-oxides and to the physiologically tolerated acid addition salts of these compounds and to pharmaceutical compositions which comprise at least one N-[(piperazinyl)hetaryl]arylsulfonamide compound as claimed in one of claims 1 to 10 and/or at least one physiologically tolerated acid addition salt of I and/or an N-oxide of I, where appropriate together with physiologically acceptable carriers and/or auxiliary substances for treating diseases which respond to influencing by dopamine D 3 receptor antagonists or agonists, in particular for treating diseases of the central nervous system and disturbances of kidney function.

  本发明涉及一般式（I）中的N-[(哌嗪基)杂芳基]芳基磺酰胺化合物，其中Q是一个双价的6元杂环芳基基团，其具有1或2个N原子作为环成员，并且可选地携带一个或两个取代基Ra，该取代基独立地选择自卤素、CN、NO2、CO2R4、COR5、C1-C4烷基和C1-C4卤代烷基；Ar是苯基或一个6元杂环芳基基团，其具有1或2个N原子作为环成员，并且可选地携带一个或两个取代基Rb，该取代基独立地选择自卤素、NO2、CN、CO2R4、COR5、C1-C6烷基、C2-C6烯基、C2-C6炔基、C3-C6环烷基、C3-C6环烷基-C1-C4烷基和C1-C4卤代烷基，其中还可能有两个与Ar相邻的C原子结合的Rb基团共同成为C3-C4烷基；R1是氢、C1-C4烷基、C1-C4卤代烷基、C3-C6环烷基、C3-C6环烷基-C1-C4烷基、C1-C4羟基烷基、C1-C4烷氧基-C1-C4烷基、C3-C4烯基或C3-C4炔基；具有在专利权要求中给出的含义的基团n、R1、R2、R3、R4和R5，以及这些化合物的N-氧化物和生理上耐受的酸加合盐，以及包含至少一种在权利要求1到10中要求的N-[(哌嗪基)杂芳基]芳基磺酰胺化合物和/或一种I的生理上耐受的酸加合盐和/或I的N-氧化物的制药组合物，如有必要，还包括用于治疗对多巴胺D3受体拮抗剂或激动剂影响有反应的疾病的生理上可接受的载体和/或辅助物质，特别是用于治疗中枢神经系统疾病和肾功能障碍。
• N-[PIPERAZINYL HETARYL]ARYLSUFONAMIDE COMPOUNDS WITH AFFINITY FOR THE DOPAMINE D3 RECEPTOR
  申请人：Braje Wilfried

  公开号：US20110294817A1

  公开（公告）日：2011-12-01

  The invention related to N-[(piperazinyl)hetaryl]arylsulfonamide compounds of the general formula (I) in which Q is a bivalent, 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R a which is/are selected, independently of each other, from halogen, CN, NO 2 , CO 2 R 4 , COR 5 , C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl; Ar is phenyl or a 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R b , which is/are selected from halogen, NO 2 , CN, CO 2 R 4 , COR 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, with it also being possible for two radicals R b which are bonded to adjacent C atoms of Ar to be together C 3 -C 4 -alkylene; R 1 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 4 -alkenyl or C 3 -C 4 -alkynyl; with the radicals n, R 1 , R 2 , R 3 , R 4 and R 5 having the meanings given in the patent claims, to the N-oxides and to the physiologically tolerated acid addition salts of these compounds and to pharmaceutical compositions which comprise at least one N-[(piperazinyl)hetaryl]arylsulfonamide compound as claimed in one of claims 1 to 10 and/or at least one physiologically tolerated acid addition salt of I and/or an N-oxide of I, where appropriate together with physiologically acceptable carriers and/or auxiliary substances for treating diseases which respond to influencing by dopamine D 3 receptor antagonists or agonists, in particular for treating diseases of the central nervous system and disturbances of kidney function.

  该发明涉及通式（I）中的N-[(哌嗪基)杂环]芳基磺酰胺化合物，其中Q是一个双价的6元杂环芳基基团，其具有1或2个N原子作为环成员，并且可选地携带一个或两个取代基Ra，这些取代基独立地从卤素，CN，NO2，CO2R4，COR5，C1-C4烷基和C1-C4卤代烷基中选择；Ar是苯基或一个6元杂环芳基基团，其具有1或2个N原子作为环成员，并且可选地携带一个或两个取代基Rb，这些取代基独立地从卤素，NO2，CN，CO2R4，COR5，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基和C1-C4卤代烷基中选择，还可以将与Ar相邻的两个Rb基团一起连接成C3-C4烷基；R1是氢，C1-C4烷基，C1-C4卤代烷基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基，C1-C4羟基烷基，C1-C4烷氧基-C1-C4烷基，C3-C4烯基或C3-C4炔基；其中，n，R1，R2，R3，R4和R5的基团具有专利权要求中所给出的含义，以及这些化合物的N-氧化物和生理上可耐受的酸加合盐以及至少包括一种N-[(哌嗪基)杂环]芳基磺酰胺化合物或I的生理上可耐受的酸加合盐和/或I的N-氧化物的药物组合物，必要时与生理上可接受的载体和/或辅助物质一起用于治疗对多巴胺D3受体拮抗剂或激动剂起反应的疾病，特别是用于治疗中枢神经系统疾病和肾功能障碍。
• N-[piperazinyl hetaryl]arylsufonamide compounds with affinity for the dopamine D3 receptor
  申请人：Braje Wilfried

  公开号：US08476275B2

  公开（公告）日：2013-07-02

  The invention related to N-[(piperazinyl)hetaryl]arylsulfonamide compounds of the general formula (I) in which Q is a bivalent, 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents Ra which is/are selected, independently of each other, from halogen, CN, NO2, CO2R4, COR5, C1-C4-alkyl and C1-C4-haloalkyl; Ar is phenyl or a 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents Rb, which is/are selected from halogen, NO2, CN, CO2R4, COR5, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl and C1-C4-haloalkyl, with it also being possible for two radicals Rb which are bonded to adjacent C atoms of Ar to be together C3-C4-alkylene; R1 is hydrogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C4-alkenyl or C3-C4-alkynyl; with the radicals n, R1, R2, R3, R4 and R5 having the meanings given in the patent claims, to the N-oxides and to the physiologically tolerated acid addition salts of these compounds and to pharmaceutical compositions which comprise at least one N-[(piperazinyl)hetaryl]arylsulfonamide compound as claimed in one of claims 1 to 10 and/or at least one physiologically tolerated acid addition salt of I and/or an N-oxide of I, where appropriate together with physiologically acceptable carriers and/or auxiliary substances for treating diseases which respond to influencing by dopamine D3 receptor antagonists or agonists, in particular for treating diseases of the central nervous system and disturbances of kidney function.

  本发明涉及一般式（I）中的N-[(哌嗪基)杂芳烃]芳基磺酰胺化合物，其中Q是具有1或2个N原子作为环成员的双价6元杂芳基基团，可选地携带一个或两个Ra取代基，所述Ra独立地选自卤素，CN，NO2，CO2R4，COR5，C1-C4烷基和C1-C4卤代烷基；Ar是苯基或具有1或2个N原子作为环成员的6元杂芳基基团，可选地携带一个或两个Rb取代基，所述Rb选自卤素，NO2，CN，CO2R4，COR5，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基和C1-C4卤代烷基，同时也可以是相邻的C原子上结合的两个Rb一起是C3-C4烷基；R1是氢，C1-C4烷基，C1-C4卤代烷基，C3-C6环烷基，C3-C6环烷基-C1-C4烷基，C1-C4羟基烷基，C1-C4烷氧基-C1-C4烷基，C3-C4烯基或C3-C4炔基；其中n，R1，R2，R3，R4和R5的基团具有专利权要求中所给出的含义，以及这些化合物的N-氧化物和生理上可容忍的酸盐，以及包括至少一种N-[(哌嗪基)杂芳烃]芳基磺酰胺化合物，如权利要求1至10中所述的化合物和/或I的生理上可容忍的酸盐和/或I的N-氧化物的制药组合物，必要时与生理上可接受的载体和/或辅助物质一起用于治疗对多巴胺D3受体拮抗剂或激动剂产生反应的疾病，特别是用于治疗中枢神经系统疾病和肾功能障碍。
• EP1613596A1
  申请人：——

  公开号：EP1613596A1

  公开（公告）日：2006-01-11
• N-[(PIPERAZINYL)HETARYL]ARYLSULFONAMIDE COMPOUNDS WITH AFFINITY FOR THE DOPAMINE D3 RECEPTOR
  申请人：Abbott GmbH & Co. KG

  公开号：EP1613596B1

  公开（公告）日：2008-03-12