2-amino-1-(5-hydroxy-2-methylphenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-amino-1-(5-hydroxy-2-methylphenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
• 英文别名: (1M)-2-amino-1-(5-hydroxy-2-methylphenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide；2-amino-1-(5-hydroxy-2-methylphenyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide
• 化学式: C₁₈H₁₅N₅O₂
• 分子量: 333.349
• InChiKey: ZHMCGBRGDVCXLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(3-chloroquinoxalin-2(1H)-ylidene)malononitrile 在 硫酸 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.5h， 生成 2-amino-1-(5-hydroxy-2-methylphenyl)-1H-pyrrolo[2,3-b]quinoxaline-3-carboxamide
  参考文献：
  名称：

  2-Amino-1-(o-tolyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide derivates

  摘要：

  该发明涉及一种具有一般式（1）特征的化合物，其中R1为OH或CH2OH。该发明进一步涉及一种包含至少一种上述化合物的药物制剂。该发明的另一个方面是将该化合物或该药物制剂用于治疗疾病的方法，特别是用于治疗癌症或眼内新生血管综合征的治疗。

  公开号：

  EP2924040A1

文献信息

• Pyrrolo[3,2-<i>b</i>]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and <i>in Vivo</i> Validation
  作者：Andrea Unzue、Jing Dong、Karine Lafleur、Hongtao Zhao、Emilie Frugier、Amedeo Caflisch、Cristina Nevado

  DOI：10.1021/jm5009242

  日期：2014.8.14

  The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I-1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I-1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.
• [EN] 2-AMINO-1-(O-TOLYL)PYRROLO[3,2-B]QUINOXALINE-3-CARBOXAMIDE DERIVATES<br/>[FR] DÉRIVÉS DE 2-AMINO-1-(O-TOLYL)PYRROLO[3,2-B]QUINOXALINE-3-CARBOXAMIDE
  申请人：UNIV ZUERICH

  公开号：WO2015144923A1

  公开（公告）日：2015-10-01

  The invention relates to a compound characterized by a general formula (1), wherein R1 is OH or CH2OH. The invention relates further to a pharmaceutical preparation comprising at least one of said compounds. A further aspect of the invention the use of said compound or said pharmaceutical preparation in a method of treatment of disease, in particular the treatment of cancer or intraocular neovascular syndromes.