[2-(5-Methylfuran-2-yl)quinolin-4-yl][4-(methylsulfonyl)piperazin-1-yl]methanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [2-(5-Methylfuran-2-yl)quinolin-4-yl][4-(methylsulfonyl)piperazin-1-yl]methanone
• 英文别名: [2-(5-methylfuran-2-yl)quinolin-4-yl]-(4-methylsulfonylpiperazin-1-yl)methanone
• 化学式: C₂₀H₂₁N₃O₄S
• mdl: MFCD04226649
• 分子量: 399.47
• InChiKey: PVVOFPOWWYAHIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [2-(5-Methylfuran-2-yl)quinolin-4-yl][4-(methylsulfonyl)piperazin-1-yl]methanone 在 air 作用下， 以 二甲基亚砜 为溶剂， 反应 912.0h， 生成 4-(4-methylsulfonylpiperazine-1-carbonyl)-1H-quinolin-2-one 、 、 、
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS OF APOBEC3G AND APOBEC3B
  [FR] INHBITEURS DE PETITES MOLÉCULES D'APOBEC3G ET D'APOBEC3B

  摘要：

  本发明涉及抑制APOBEC相关的DNA胞嘧啶脱氨酶酶的组合物和方法，以及使用这些化合物治疗患者的疾病的方法，例如感染性疾病或癌症。感染性疾病可以是病毒性疾病，例如HIV，也可以是癌症，例如乳腺癌、膀胱癌、宫颈癌、头颈部肿瘤或肺鳞状细胞癌或肺腺癌。

  公开号：

  WO2015106272A1

文献信息

• Oxidative Reactivities of 2-Furylquinolines: Ubiquitous Scaffolds in Common High-Throughput Screening Libraries
  作者：Margaret E. Olson、Daniel Abate-Pella、Angela L. Perkins、Ming Li、Michael A. Carpenter、Anurag Rathore、Reuben S. Harris、Daniel A. Harki

  DOI：10.1021/acs.jmedchem.5b00930

  日期：2015.9.24

  High-throughput screening (HTS) was employed to discover APOBEC3G inhibitors, and multiple 2-furylquinolines (e.g., 1) were found. Dose response assays with 1 from the HTS sample, as well as commercial material, yielded similar confirmatory results. Interestingly, freshly synthesized and DMSO-solubilized 1 was inactive. Repeated screening of the DMSO aliquot of synthesized 1 revealed increasing APOBEC3G inhibitory activity with age, suggesting that 1 decomposes into an active inhibitor. Laboratory aging of 1 followed by analysis revealed that 1 undergoes oxidative decomposition in air, resulting from a [4 + 2] cycloaddition between the furan of 1 and O-1(2). The resulting endoperoxide then undergoes additional transformations, highlighted by Baeyer-Villager rearrangements, to deliver lactam, carboxylic acid, and aldehyde products. The endoperoxide also undergoes hydrolytic opening followed by further transformations to a bis-enone. Eight structurally related analogues from HTS libraries were similarly reactive. This study constitutes a cautionary tale to validate 2-furylquinolines for structure and stability prior to chemical optimization campaigns.
• [EN] SMALL MOLECULE INHIBITORS OF APOBEC3G AND APOBEC3B<br/>[FR] INHBITEURS DE PETITES MOLÉCULES D'APOBEC3G ET D'APOBEC3B
  申请人：HARKI DANIEL A

  公开号：WO2015106272A1

  公开（公告）日：2015-07-16

  The present invention is directed to compositions and methods for inhibition of APOBEC-related DNA cytosine deaminase enzymes, and to methods of using the compounds for treatment of a disease in a patient, such as an infectious disease or a cancer. The infectious disease can be a viral disease, e.g., HIV, or can be a cancer, such as a breast, bladder, cervical, head, or neck cancer, or a lung squamous cell carcinoma or lung adenocarcinoma.

  本发明涉及抑制APOBEC相关的DNA胞嘧啶脱氨酶酶的组合物和方法，以及使用这些化合物治疗患者的疾病的方法，例如感染性疾病或癌症。感染性疾病可以是病毒性疾病，例如HIV，也可以是癌症，例如乳腺癌、膀胱癌、宫颈癌、头颈部肿瘤或肺鳞状细胞癌或肺腺癌。