methyl 2-(4-bromophenyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate | 857665-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: methyl 2-(4-bromophenyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate
• 英文别名: methyl 2-(4-bromophenyl)-5-hydroxy-6-oxo-1H-pyrimidine-4-carboxylate
• CAS: 857665-06-6
• 化学式: C₁₂H₉BrN₂O₄
• 分子量: 325.118
• InChiKey: CGPVNXFUTMOQOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-bromophenyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以86 %的产率得到2-(4-Bromophenyl)-5,6-dihydroxypyrimidine-4-carboxylic acid
  参考文献：
  名称：

  基于片段的新型 MUS81 抑制剂的发现

  摘要：

  MUS81 是一种结构选择性核酸内切酶，可切割同源重组和有丝分裂等自然生理过程产生的各种分支 DNA 结构。因此，MUS81 能够缓解复制压力，据报道，其功能对于许多癌症的生存至关重要，特别是那些 DNA 修复机制功能失调的癌症。因此，人们对 MUS81 作为癌症药物靶点感兴趣，但目前很少有这种酶的小分子抑制剂报道，并且没有配体晶体结构可用于指导命中优化。在这里，我们报告了基于片段的新型小分子 MUS81 抑制剂的发现，其具有亚μM 生化活性。这些抑制剂被用来开发一种新型晶体系统，为小分子抑制 MUS81 提供了第一个结构见解。

  DOI：

  10.1021/acsmedchemlett.3c00453
• 作为产物：
  描述：

  (E)-4-溴-N’-羟基苄脒 以 5,5-dimethyl-1,3-cyclohexadiene 、 氯仿 为溶剂， 反应 41.0h， 生成 methyl 2-(4-bromophenyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate
  参考文献：
  名称：

  基于片段的新型 MUS81 抑制剂的发现

  摘要：

  MUS81 是一种结构选择性核酸内切酶，可切割同源重组和有丝分裂等自然生理过程产生的各种分支 DNA 结构。因此，MUS81 能够缓解复制压力，据报道，其功能对于许多癌症的生存至关重要，特别是那些 DNA 修复机制功能失调的癌症。因此，人们对 MUS81 作为癌症药物靶点感兴趣，但目前很少有这种酶的小分子抑制剂报道，并且没有配体晶体结构可用于指导命中优化。在这里，我们报告了基于片段的新型小分子 MUS81 抑制剂的发现，其具有亚μM 生化活性。这些抑制剂被用来开发一种新型晶体系统，为小分子抑制 MUS81 提供了第一个结构见解。

  DOI：

  10.1021/acsmedchemlett.3c00453

文献信息

• EP1698628
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase
  作者：Daoguang Zhang、Bikash Debnath、Shenghui Yu、Tino Wilson Sanchez、Frauke Christ、Yang Liu、Zeger Debyser、Nouri Neamati、Guisen Zhao

  DOI：10.1016/j.bmc.2014.07.036

  日期：2014.10

  Raltegravir (RAL) is a first clinically approved integrase (IN) inhibitor for the treatment of HIV but rapid mutation of the virus has led to chemo-resistant strains. Therefore, there is a medical need to develop new IN inhibitors to overcome drug resistance. At present, several IN inhibitors are in different phases of clinical trials and few have been discontinued due to toxicity and lack of efficacy. The development of potent second-generation IN inhibitors with improved safety profiles is key for selecting new clinical candidates. In this article, we report the design and synthesis of potent 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide analogues as second-generation IN inhibitors. These compounds satisfy two structural requirements known for potent inhibition of HIV-1 IN catalysis: a metal chelating moiety and a hydrophobic functionality necessary for selectivity against the strand transfer reaction. Most of the new compounds described herein are potent and selective for the strand transfer reaction and show antiviral activity in cell-based assays. Furthermore, this class of compounds are drug-like and suitable for further optimization and preclinical studies.
• Enols as Feasible Acid Components in the Ugi Condensation
  作者：Teresa G. Castellano、Ana G. Neo、Stefano Marcaccini、Carlos F. Marcos

  DOI：10.1021/ol302976g

  日期：2012.12.21

  Heterocyclic enols are used for the first time as acid components in an Ugi-type multicomponent condensation. For that purpose, we have chosen enols containing a Michael acceptor, in order to facilitate an irreversible rearrangement of the primary Ugi adduct. The new four-component process leads readily and efficiently to heterocyclic enamines containing at least six elements of diversity.
• Hydroxypyrimidinone derivatives having inhibitory activity against hiv integrase
  申请人：Mikamiyama Hidenori

  公开号：US20070149556A1

  公开（公告）日：2007-06-28

  Compounds of Formula (1), pharmaceuticals containing the same, especially anti-HIV agents having anti viral activity, especially inhibitory activity against HIV integrase, wherein X represents either one of the following groups: (wherein, C ring is nitrogen-containing aromatic heterocyclic ring in which at least one atom in atoms neighboring the atom bound to the pyrimidine ring is unsubstituted nitrogen atom; R 10 is hydrogen or lower alkyl; D ring is aryl or heteroaryl) Z 1 and Z 3 each is independently a single bond, O, S, S (═O) or SO 2 ; Z 2 is a single bond, lower alkylene or lower alkenylene; Ar is optionally substituted aryl or optionally substituted heteroaryl; R 1 is lower alkyl, substituted lower alkyl or the like; R 2 is a hydrogen atom or optionally substituted lower alkyl; or R 1 and R 2 may form, together with an adjacent atom, an optionally substituted heterocyclic ring, a pharmaceutically acceptable salt or a solvate thereof.
• Hydroxypyrimidinone derivatives having inhibitory activity against HIV integrase
  申请人：Mikamiyama Hidenori

  公开号：US20100204237A1

  公开（公告）日：2010-08-12

  Compounds of Formula (1), pharmaceuticals containing the same, especially anti-HIV agents having anti viral activity, especially inhibitory activity against HIV integrase, wherein X represents either one of the following groups: (wherein, C ring is nitrogen-containing aromatic heterocyclic ring in which at least one atom in atoms neighboring the atom bound to the pyrimidine ring is unsubstituted nitrogen atom; R 10 is hydrogen or lower alkyl; D ring is aryl or heteroaryl) Z 1 and Z 3 each is independently a single bond, O, S, S(═O) or SO 2 ; Z 2 is a single bond, lower alkylene or lower alkenylene; Ar is optionally substituted aryl or optionally substituted heteroaryl; R 1 is lower alkyl, substituted lower alkyl or the like; R 2 is a hydrogen atom or optionally substituted lower alkyl; or R 1 and R 2 may form, together with an adjacent atom, an optionally substituted heterocyclic ring, a pharmaceutically acceptable salt or a solvate thereof.