(4-chloro-benzimidoylaminooxy)-butenedioic acid dimethyl ester | 33229-30-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-chloro-benzimidoylaminooxy)-butenedioic acid dimethyl ester
• 英文别名: dimethyl 2-[(Z)-[amino-(4-chlorophenyl)methylidene]amino]oxybut-2-enedioate
• CAS: 33229-30-0
• 化学式: C₁₃H₁₃ClN₂O₅
• 分子量: 312.71
• InChiKey: HJUXUYBTPUSTAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-chloro-benzimidoylaminooxy)-butenedioic acid dimethyl ester 以 邻二甲苯 为溶剂， 生成 methyl 2-(4-chlorophenyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate
  参考文献：
  名称：

  HIV-1逆转录酶抑制剂的药理学要求，该抑制剂可在聚合催化周期中选择性地“冻结”预转移的复合物

  摘要：

  逆转录酶（RT）负责复制HIV-1基因组，并且是经验证的治疗HIV感染的治疗靶标。在RT催化的DNA聚合过程的每个循环中，无机焦磷酸盐作为核苷酸掺入的副产物释放。鉴定出的小分子充当焦磷酸盐的生物等排体，并且可以在DNA或RNA模板引物酶复合物的预易位阶段选择性冻结HIV-1 RT的催化循环。

  DOI：

  10.1016/j.bmc.2018.02.017
• 作为产物：
  描述：

  对氯苯甲腈 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 (4-chloro-benzimidoylaminooxy)-butenedioic acid dimethyl ester
  参考文献：
  名称：

  HIV-1逆转录酶抑制剂的药理学要求，该抑制剂可在聚合催化周期中选择性地“冻结”预转移的复合物

  摘要：

  逆转录酶（RT）负责复制HIV-1基因组，并且是经验证的治疗HIV感染的治疗靶标。在RT催化的DNA聚合过程的每个循环中，无机焦磷酸盐作为核苷酸掺入的副产物释放。鉴定出的小分子充当焦磷酸盐的生物等排体，并且可以在DNA或RNA模板引物酶复合物的预易位阶段选择性冻结HIV-1 RT的催化循环。

  DOI：

  10.1016/j.bmc.2018.02.017

文献信息

• Synthesis of 1,2,4-oxadiazines and their rearrangement to pyrimidines
  作者：Arthur A. Santilli、Anthony C. Scotese

  DOI：10.1002/jhet.5570160202

  日期：1979.3

  Several amide oximes underwent condensation reactions with dimethyl acetylene dicarboxylate to afford 1:1 adducts. Under basic conditions, these adducts underwent ring closure to afford several methyl [3-(substituted)-4,5-dihydro-5-oxo-6H-1,2,4-oxadiazin-6-ylidene]acetates. The reactions of these compounds with a variety of amines resulted in addition-rearrangement reactions with the formation of the

  几种酰胺肟与乙炔二甲酸二甲酯进行缩合反应，得到1：1的加合物。在碱性条件下，对这些加合物进行闭环反应，得到几种[3-（取代）-4,5-二氢-5-氧代-6 H -1,2,4-氧二嗪-6-亚烷基]乙酸甲酯。这些化合物与多种胺的反应导致加成-重排反应，形成相应的甲基2-取代的5-取代的氨基-1,6-二氢-6-氧代-4-嘧啶羧酸酯。
• 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.
• Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “Freeze” the pre-translocated complex during the polymerization catalytic cycle
  作者：Cyrus M. Lacbay、Michael Menni、Jean A. Bernatchez、Matthias Götte、Youla S. Tsantrizos

  DOI：10.1016/j.bmc.2018.02.017

  日期：2018.5

  Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the

  逆转录酶（RT）负责复制HIV-1基因组，并且是经验证的治疗HIV感染的治疗靶标。在RT催化的DNA聚合过程的每个循环中，无机焦磷酸盐作为核苷酸掺入的副产物释放。鉴定出的小分子充当焦磷酸盐的生物等排体，并且可以在DNA或RNA模板引物酶复合物的预易位阶段选择性冻结HIV-1 RT的催化循环。
• 10.1021/acsmedchemlett.3c00453
  作者：Collie, Gavin W.、Börjesson, Ulf、Chen, Yunhua、Dong, Zhiqiang、Di Fruscia, Paolo、Gohlke, Andrea、Hoyle, Anna、Hunt, Thomas A.、Jesani, Mehul H.、Luo, Haiou、Luptak, Jakub、Milbradt, Alexander G.、Narasimhan, Priyanka、Packer, Martin、Patel, Saleha、Qiao, Jingchuan、Storer, R. Ian、Stubbs, Christopher J.、Tart, Jonathan、Truman, Caroline、Wang, Anderson T.、Wheeler, Matthew G.、Winter-Holt, Jon

  DOI：10.1021/acsmedchemlett.3c00453

  日期：——

  cancer drug target, yet there are currently few small molecule inhibitors of this enzyme reported, and no liganded crystal structures are available to guide hit optimization. Here we report the fragment-based discovery of novel small molecule MUS81 inhibitors with sub-μM biochemical activity. These inhibitors were used to develop a novel crystal system, providing the first structural insight into the

  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。