N-(5-ethyl-1,3,4-oxadiazol-2-yl)-2-phenyl-4-quinolinecarboxamide | 1236056-68-0

• 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: N-(5-ethyl-1,3,4-oxadiazol-2-yl)-2-phenyl-4-quinolinecarboxamide
• 英文别名: N-(5-ethyl-1,3,4-oxadiazol-2-yl)-2-phenylquinoline-4-carboxamide
• CAS: 1236056-68-0
• 化学式: C₂₀H₁₆N₄O₂
• 分子量: 344.373
• InChiKey: QEHJBVYJXUYUBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-苯基-4-喹啉羧酸 、 2-氨基-5-乙基-1,3,4-氧二唑 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(5-ethyl-1,3,4-oxadiazol-2-yl)-2-phenyl-4-quinolinecarboxamide
  参考文献：
  名称：

  Identification of a New Series of STAT3 Inhibitors by Virtual Screening

  摘要：

  The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3 In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay STX-0119 selectively abrogated the DNA binding activity of STAT3 and suppressed the expression of STAT3-regulated oncoproteins such as c-myc and survivin in cancer cells. In contrast a truncated inactive analogue, STX-0872, did not exhibit those activites, Oral administration of STX-0119 effectively abrogated the growth of human lymphoma cells in a SCC-3 subcutaneous xenograft model without visible toxicity Structure-activity relationships of STX-0119 derivatives were investigated using the docking model of the STAT3-SH2 domain/STX-0119.

  DOI：

  10.1021/ml1000273

文献信息

• STAT3 INHIBITOR CONTAINING QUINOLINECARBOXAMIDE DERIVATIVE AS ACTIVE INGREDIENT
  申请人：General Incorporated Association Pharma Valley Project Supporting Organization

  公开号：EP2325181B1

  公开（公告）日：2017-03-29
• US8466290B2
  申请人：——

  公开号：US8466290B2

  公开（公告）日：2013-06-18
• Identification of a New Series of STAT3 Inhibitors by Virtual Screening
  作者：Kenji Matsuno、Yoshiaki Masuda、Yutaka Uehara、Hiroshi Sato、Ayumu Muroya、Osamu Takahashi、Takane Yokotagawa、Toshio Furuya、Tadashi Okawara、Masami Otsuka、Naohisa Ogo、Tadashi Ashizawa、Chie Oshita、Sachiko Tai、Hidee Ishii、Yasuto Akiyama、Akira Asai

  DOI：10.1021/ml1000273

  日期：2010.11.11

  The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3 In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay STX-0119 selectively abrogated the DNA binding activity of STAT3 and suppressed the expression of STAT3-regulated oncoproteins such as c-myc and survivin in cancer cells. In contrast a truncated inactive analogue, STX-0872, did not exhibit those activites, Oral administration of STX-0119 effectively abrogated the growth of human lymphoma cells in a SCC-3 subcutaneous xenograft model without visible toxicity Structure-activity relationships of STX-0119 derivatives were investigated using the docking model of the STAT3-SH2 domain/STX-0119.