2-(4-甲基哌嗪基)-6-硝基苯甲腈 | 63365-16-2

• 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: 2-(4-甲基哌嗪基)-6-硝基苯甲腈
• 英文名称: 2-(4-methylpiperazinyl)-6-nitrobenzenecarbonitrile
• 英文别名: 2-(4-Methyl-1-piperazinyl)-6-nitrobenzonitrile；2-(4-methylpiperazin-1-yl)-6-nitrobenzonitrile
• CAS: 63365-16-2
• 化学式: C₁₂H₁₄N₄O₂
• 分子量: 246.269
• InChiKey: YIEVTWZFLULETM-UHFFFAOYSA-N

物化性质

• 熔点：
  126-129 °C(Solv: benzene (71-43-2); hexane (110-54-3))
• 沸点：
  433.9±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-甲基哌嗪基)-6-硝基苯甲腈 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 以28%的产率得到2-氨基-6-(4-甲基-1-哌嗪基)苯腈
  参考文献：
  名称：

  Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

  摘要：

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.

  DOI：

  10.1021/jm800790t
• 作为产物：
  描述：

  N-甲基哌嗪 、 2,6-二硝基苯腈 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到2-(4-甲基哌嗪基)-6-硝基苯甲腈
  参考文献：
  名称：

  Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

  摘要：

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.

  DOI：

  10.1021/jm800790t

文献信息

• 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use
  申请人：——

  公开号：US20030229068A1

  公开（公告）日：2003-12-11

  Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选定的化合物对于治疗疾病，如细胞增殖或凋亡介导的疾病，具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的衍生物，药物组合物以及预防和治疗涉及中风、癌症等疾病和其他疾病或病症的方法。该发明还涉及制备这些化合物的方法，以及在这些方法中有用的中间体。
• 2-Cyano-3- or 4-(substituted amino)oxanilic acid derivatives
  申请人：American Home Products Corporation

  公开号：US04087606A1

  公开（公告）日：1978-05-02

  The 2-cyano-3-or 4-(substituted amino) oxanilic acid derivatives of the formula: ##STR1## in which the group ##STR2## appears in the designated 3- or 4- position and R is --H; an alkali metal; .sup.+ NH.sub.4 ; alkyl of 1 to 6 carbon atoms, inclusive; aralkyl of 7 or 8 carbon atoms; or cycloalkyl of 5 or 6 carbon atoms; R.sup.1 is --H or alkyl of 1 to 9 carbon atoms; R.sup.2 is --H, alkyl of 1 to 9 carbon atoms or cycloalkyl of 3 to 6 carbon atoms; R.sup.1 and R.sup.2, together, with the nitrogen atom to which they are attached, are aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 4-lower alkyl-piperazinyl, morpholino or thiomorpholino; And pharmaceutically acceptable acid addition salts thereof are anti-allergic agents.

  公式为：##STR1##的2-氰基-3-或4-(取代氨基)氧化苯乙酸衍生物，其中基团##STR2##出现在指定的3-或4-位置，R为--H；碱金属；.sup.+ NH.sub.4；1至6个碳原子的烷基，包括；7或8个碳原子的芳基烷基；或5或6个碳原子的环烷基；R.sup.1为--H或1至9个碳原子的烷基；R.sup.2为--H，1至9个碳原子的烷基或3至6个碳原子的环烷基；R.sup.1和R.sup.2与它们附着的氮原子一起，是氮杂环丙基，氮杂环戊基，吡咯烷基，哌啶基，哌嗪基，4-低烷基哌嗪基，吗啉或硫代吗啉；以及其药学上可接受的酸盐是抗过敏剂。
• 2-Cyano-3-or 4-(substituted amino)oxanilic acid derivatives
  申请人：American Home Products Corporation

  公开号：US04054591A1

  公开（公告）日：1977-10-18

  The 2-cyano-3-or 4-(substituted amino)oxanilic acid derivatives of the formula: ##STR1## in which the group ##STR2## appears in the designated 3- or 4- position and R is -H; an alkali metal; .sup.+ NH.sub.4 ; alkyl of 1 to 6 carbon atoms, inclusive; aralkyl of 7 or 8 carbon atoms; or cycloalkyl of 5 or 6 carbon atoms; R.sup.1 is --H or alkyl of 1 to 9 carbon atoms; R.sup.2 is --H, alkyl of 1 to 9 carbon atoms or cycloalkyl of 3 to 6 carbon atoms; R.sup.1 and R.sup.2, together, with the nitrogen atom to which they are attached, are aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 4-lower alkyl-piperazinyl, morpholino or thiomorpholino; and pharmaceutically acceptable acid addition salts thereof are anti-allergic agents.

  公式为：##STR1## 的2-氰基-3-或4-(取代氨基)氧化邻苯二甲酸衍生物，其中组 ##STR2## 出现在指定的3-或4-位置，R为-H；碱金属；.sup.+ NH.sub.4；1至6个碳原子的烷基，包括；7或8个碳原子的芳基烷基；或5或6个碳原子的环烷基；R.sup.1为--H或1至9个碳原子的烷基；R.sup.2为--H，1至9个碳原子的烷基或3至6个碳原子的环烷基；R.sup.1和R.sup.2与它们所连接的氮原子一起，是氮杂环丙烷基，氮杂环戊烷基，吡咯烷基，哌啶基，哌嗪基，4-低烷基哌嗪基，吗啉基或硫代吗啉基；以及其药学上可接受的酸盐是抗过敏剂。
• Structure–activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors
  作者：Robert M. Rzasa、Matthew R. Kaller、Gang Liu、Ella Magal、Thomas T. Nguyen、Timothy D. Osslund、David Powers、Vincent J. Santora、Vellarkad N. Viswanadhan、Hui-Ling Wang、Xiaoling Xiong、Wenge Zhong、Mark H. Norman

  DOI：10.1016/j.bmc.2007.07.005

  日期：2007.10

  Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that plays a critical role in the early development of the nervous system. Deregulation of CDK5 is believed to contribute to the abnormal phosphorylation of various cellular substrates associated with neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. In this investigation we present our synthetic studies toward this series of compounds and discuss their biological relevance as CDK5 inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.
• N-(Aminophenyl)oxamic acids and esters as potent, orally active antiallergy agents
  作者：Dieter H. Klaubert、John H. Sellstedt、Charles J. Guinosso、Robert J. Capetola、Stanley C. Bell

  DOI：10.1021/jm00138a020

  日期：1981.6