4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide
• 英文别名: N-{4-[(3-bromophenyl)amino]quinazoline-6-yl}4-(dimethylamino)-2-butenamide；N-[4-(3-bromoanilino)quinazolin-6-yl]-4-(dimethylamino)but-2-enamide
• 化学式: C₂₀H₂₀BrN₅O
• 分子量: 426.316
• InChiKey: ZCIXBBSRVLSRJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide 、 对硝基溴化苄 以 四氢呋喃 为溶剂， 反应 24.0h， 以45%的产率得到(2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-(4-nitrobenzyl)-4-oxo-2-buten-1-ammonium bromide
  参考文献：
  名称：

  Synthesis of substituted 5-bromomethyl-4-nitroimidazoles and use for the preparation of the hypoxia-selective multikinase inhibitor SN29966

  摘要：

  5-Bromomethyl-4-nitroimidazoles have utility as bioreductive trigger precursors for the preparation of hypoxia-selective prodrugs. Here we describe an efficient two-step synthesis of 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole, a preferred precursor, employing an N-bromosuccinimide mediated radical bromination. Use of this precursor to prepare SN29966, a promising hypoxia-selective irreversible pan-ErbB inhibitor is reported along with the preparation of four other prodrug candidates. 5-Bromomethyl-4-nitroimidazole analogues bearing electron-donating and electron-withdrawing substituents at the N-1 and C-2 positions are also described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.08.037
• 作为产物：
  描述：

  4-bromo-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide 、 二甲胺 在 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以44%的产率得到4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide
  参考文献：
  名称：

  SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS TYROSINE KINASE INHIBITORS

  摘要：

  公开号：

  EP1000039B1

文献信息

• Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy
  申请人：——

  公开号：US20040265228A1

  公开（公告）日：2004-12-30

  Radiolabeled epidermal growth factor receptor tyrosine kinase (EGFR-TK) irreversible inhibitors and their use as biomarkers for medicinal radioimaging such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) and as radiopharmaceuticals for radiotherapy are disclosed.

  本发明公开了放射性标记的表皮生长因子受体酪氨酸激酶（EGFR-TK）不可逆抑制剂及其用作医学放射成像的生物标志物，例如正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT），以及作为放射性药物用于放射治疗。
• Substituted quinazoline derivatives
  申请人：American Cyanamid Company

  公开号：US06251912B1

  公开（公告）日：2001-06-26

  This invention provides compounds of formula 1 having the structure wherein: X, R1, R2, R3, R4, Z, X, and n are as defined hereinbefore in the specification, which are useful as antineoplastic agents and in the treatment of certain kidney diseases, such as polycystic kidney disease.

  本发明提供了具有公式1的化合物，其结构如下：其中X，R1，R2，R3，R4，Z，X和n如本说明书中所定义，这些化合物可用作抗肿瘤剂，并用于治疗某些肾脏疾病，如多囊肾病。
• PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  申请人：Smaill Jeffrey Bruce

  公开号：US20120077811A1

  公开（公告）日：2012-03-29

  The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R 1 is a group of the formula —(CH 2 ) n Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH 2 ) n Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R 2 , R 3 and R 4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R 2 )(R 3 )(R 4 )N, or two of R 2 , R 3 , and R 4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R 2 , R 3 and R 4 may be absent and two of R 2 , R 3 and R 4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

  本发明提供了新型的前药化合物，包括一种激酶抑制剂和一种还原活化的破裂芳香族硝基杂环或芳香族硝基碳杂环触发剂，其中该化合物带有正电荷。在优选实施例中，该化合物为式I：其中：X是任何带负电的反离子；R1是公式—(CH2)nTr的基团，其中Tr是芳香族硝基杂环或芳香族硝基碳杂环，—(CH2)nTr作为还原活化的破裂触发器；n是0到6的整数；R2、R3和R4可以各自独立地选择来自三级胺激酶抑制剂的脂肪族或芳香族基团(R2)(R3)(R4)N，或者R2、R3和R4中的两个可以形成激酶抑制剂的脂肪族或芳香族杂环胺环，或者R2、R3和R4中的一个可以缺失，R2、R3和R4中的两个可以形成激酶抑制剂的芳香族杂环胺环。该发明的化合物可用于治疗增殖性疾病，如癌症。
• EP1411993A4
  申请人：——

  公开号：EP1411993A4

  公开（公告）日：2007-08-01
• RADIOLABELED IRREVERSIBLE INHIBITORS OF EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE AND THEIR USE IN RADIOIMAGING AND RADIOTHERAPY
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANYOF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP1411993A2

  公开（公告）日：2004-04-28