4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide | 1245555-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide
• 英文别名: 6-(2,6-dichlorophenyl)-8-methyl-2-[[1-[(3-methyl-5-nitroimidazol-4-yl)methyl]pyridin-1-ium-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one;bromide
• CAS: 1245555-36-5
• 化学式: Br*C₂₄H₁₉Cl₂N₈O₃
• 分子量: 618.277
• InChiKey: XUAJZZPDBBWLRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(bromomethyl)-1-methyl-4-nitro-1H-imidazole 、 6-(2,6-Dichlorophenyl)-8-methyl-2-(pyridin-4-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 600.0h， 以65%的产率得到4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide
  参考文献：
  名称：

  [EN] PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  [FR] FORMES PROMÉDICAMENTS D'INHIBITEURS DE KINASE ET LEUR UTILISATION EN THÉRAPIE

  摘要：

  公开号：

  WO2010104406A8

文献信息

• 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。
• Prodrug forms of kinase inhibitors and their use in therapy
  申请人：Smaill Jeffrey Bruce

  公开号：US09073916B2

  公开（公告）日：2015-07-07

  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; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 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，其中包含一种激酶抑制剂和一种还原活化的分裂芳香族硝基杂环或芳香族硝基碳环触发剂，该化合物带有正电荷。在优选实施例中，该化合物为公式I：其中：X是任何负电荷的反离子；R1是公式—（CH2）nTr的基团，其中Tr是一种芳香族硝基杂环或芳香族硝基碳环，—（CH2）nTr作为还原活化的分裂触发剂；n是从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（R2）（R3）（R4）N的脂肪族或芳香族基团，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中的一个可能不存在，并且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。本发明的化合物在治疗癌症等增殖性疾病方面是有用的。
• COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING HER-DRIVEN DRUG-RESISTANT CANCERS
  申请人：The Regents of The University of Colorado, A Body Corporate

  公开号：EP3679063A1

  公开（公告）日：2020-07-15
• COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING HER-DRIVEN CANCERS
  申请人：Rain Therapeutics Inc.

  公开号：EP3847283A2

  公开（公告）日：2021-07-14
• US9073916B2
  申请人：——

  公开号：US9073916B2

  公开（公告）日：2015-07-07