N-(5-(2-furyl)-1,3,4-oxadiazol-2-yl)-2-(1-naphthyl)-4-quinolinecarboxamide | 1204211-82-4

• 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-(2-furyl)-1,3,4-oxadiazol-2-yl)-2-(1-naphthyl)-4-quinolinecarboxamide
• 英文别名: N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(1-naphthyl)-4-quinolinecarboxamide；N-[5-(furan-2-yl)-1,3,4-oxadiazol-2-yl]-2-naphthalen-1-ylquinoline-4-carboxamide
• CAS: 1204211-82-4
• 化学式: C₂₆H₁₆N₄O₃
• 分子量: 432.438
• InChiKey: WJWGIMDGOPMMMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-呋喃-2-1,3,4 -恶二唑-2-氨基 、 2-萘-1-喹啉-4-羧酸 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-(2-furyl)-1,3,4-oxadiazol-2-yl)-2-(1-naphthyl)-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

• CANCER COMBINATION THERAPY USING QUINOLINE CARBOXAMIDE DERIVATIVE
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP3854397A1

  公开（公告）日：2021-07-28

  Provided is a method for using a STAT3 inhibitor having a high antitumor effect and little side effects. The antitumor agent comprises a combination of a quinoline carboxamide derivative of formula (I) below or a pharmacologically acceptable salt thereof with one or more cancer molecular target drugs selected from the group consisting of an ALK inhibitor, an EGFR inhibitor, a multi kinase inhibitor, a HER2/EGFR inhibitor, an mTOR inhibitor, a BRAF inhibitor, a MEK inhibitor and a BCR-ABL inhibitor, wherein R1, R2, R3, R4, R5 and R6 are the same or different, and each represent a hydrogen atom, a substituted or unsubstituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, COOR7 (wherein R7 represents a substituted or unsubstituted alkyl group), or OR8 (wherein R8 represents a substituted or unsubstituted alkyl group).

  本发明提供了一种使用 STAT3 抑制剂的方法，该抑制剂具有较高的抗肿瘤效果且副作用小。该抗肿瘤药包括下式(I)的喹啉羧酰胺衍生物或其药理学上可接受的盐与一种或多种选自由 ALK 抑制剂、表皮生长因子受体抑制剂、多激酶抑制剂、HER2/EGFR 抑制剂、mTOR 抑制剂、BRAF 抑制剂、MEK 抑制剂和 BCR-ABL 抑制剂组成的组的癌症分子靶向药物的组合、MEK抑制剂和BCR-ABL抑制剂，其中R1、R2、R3、R4、R5和R6相同或不同，各自代表氢原子、取代或未取代的芳基、取代或未取代的芳杂环基、COOR7（其中R7代表取代或未取代的烷基）或OR8（其中R8代表取代或未取代的烷基）。
• IMMUNE CHECKPOINT INHIBITOR COMBINATION THERAPY USING QUINOLINE CARBOXAMIDE DERIVATIVE
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP3960199A1

  公开（公告）日：2022-03-02

  Provided is a method for using a STAT3 inhibitor which exhibits an excellent antitumor effect. An antitumor agent comprises a quinoline carboxamide derivative of formula (I) below or a salt thereof as an active ingredient, and is administered in combination with an immune checkpoint inhibitor. The antitumor agent is administered before the administration of the immune checkpoint inhibitor.

  本发明提供了一种 STAT3 抑制剂的使用方法，该抑制剂具有优异的抗肿瘤效果。一种抗肿瘤制剂包括以下式（I）的喹啉羧酰胺衍生物或其盐作为活性成分，并与免疫检查点抑制剂联合给药。抗肿瘤剂在使用免疫检查点抑制剂之前使用。
• 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
• [EN] CANCER COMBINATION THERAPY USING QUINOLINE CARBOXAMIDE DERIVATIVE<br/>[FR] POLYTHÉRAPIE ANTICANCÉREUSE UTILISANT UN DÉRIVÉ DE QUINOLÉINE CARBOXAMIDE<br/>[JA] キノリンカルボキサミド誘導体を用いるがん併用療法
  申请人：YAKULT HONSHA KK

  公开号：WO2020059705A1

  公开（公告）日：2020-03-26

  抗腫瘍効果が高く且つ副作用の少ないＳＴＡＴ３阻害剤の使用方法を提供する。　下記式（Ｉ）： 〔式中、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５及びＲ６は、同一又は異なって、水素原子、置換若しくは非置換アリール基、置換若しくは非置換芳香族複素環基、ＣＯＯＲ７（式中、Ｒ７は、置換若しくは非置換アルキル基を示す。）、又はＯＲ８（式中、Ｒ８は置換若しくは非置換アルキル基を示す。）を示す。〕 で表されるキノリンカルボキサミド誘導体又はそれらの薬理学的に許容される塩と、ＡＬＫ阻害剤、ＥＧＦＲ阻害剤、Ｍｕｌｔｉ　ｋｉｎａｓｅ阻害剤、ＨＥＲ２／ＥＧＦＲ阻害剤、ｍＴＯＲ阻害剤、ＢＲＡＦ阻害剤、ＭＥＫ阻害剤及びＢＣＲ－ＡＢＬ阻害剤から選ばれる１以上のがん分子標的薬を組み合わせてなる抗腫瘍剤。