2-amino-4-(4-bromothenyloxy)-6-[N-(4-(4-aminophenylamino)anilino)]-5-nitropyrimidine | 1292320-46-7

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-amino-4-(4-bromothenyloxy)-6-[N-(4-(4-aminophenylamino)anilino)]-5-nitropyrimidine
• 英文别名: 4-N-[4-(4-aminoanilino)phenyl]-6-[(4-bromothiophen-2-yl)methoxy]-5-nitropyrimidine-2,4-diamine
• CAS: 1292320-46-7
• 化学式: C₂₁H₁₈BrN₇O₃S
• 分子量: 528.389
• InChiKey: YUKYAOCOEPTCIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  185
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (4-溴-2-噻吩基)甲醇 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 2-amino-4-(4-bromothenyloxy)-6-[N-(4-(4-aminophenylamino)anilino)]-5-nitropyrimidine
  参考文献：
  名称：

  Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators

  摘要：

  Searching for a novel family of inactivators of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.038

文献信息

• Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators
  作者：Sergio Lopez、Geoffrey P. Margison、R. Stanley McElhinney、Alessandra Cordeiro、T. Brian H. McMurry、Isabel Rozas

  DOI：10.1016/j.bmc.2011.01.038

  日期：2011.3

  Searching for a novel family of inactivators of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems. (C) 2011 Elsevier Ltd. All rights reserved.