4-(piperazin-1-yl)quinolin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(piperazin-1-yl)quinolin-2-amine
• 英文别名: 4-piperazin-1-ylquinolin-2-amine
• 化学式: C₁₃H₁₆N₄
• 分子量: 228.297
• InChiKey: KNBCGROIEFXNMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯喹啉-N-氧化物 在 4-甲苯磺酸酐 、 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 3.5h， 生成 4-(piperazin-1-yl)quinolin-2-amine
  参考文献：
  名称：

  Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery

  摘要：

  Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phox(SH3A-B)) with K-D values of 400-600 mu M. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phox(SH3A-B) and these competed with p22phox for binding to p47phox(SH3A-B). Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phox(SH3A-B)-p22phox interaction (K-i of 20 mu M). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.

  DOI：

  10.1021/acs.jmedchem.9b01492

文献信息

• Proline derivatives and use thereof as drugs
  申请人：Kitajima Hiroshi

  公开号：US20050245538A1

  公开（公告）日：2005-11-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗效果的化合物，其作用是通过DPP-IV的抑制作用，并且作为药物产品具有令人满意的效果。本发明人发现，在丙氨酸的γ位上引入取代基的衍生物具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• Proline derivatives and the use thereof as drugs
  申请人：——

  公开号：US20040106655A1

  公开（公告）日：2004-06-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the &ggr;-position of proline represented by the formula (I) 1 wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗作用的化合物，由于DPP-IV抑制作用而具有满意的药物产品。本发明人发现，具有引入取代基的脯氨酸γ-位置的衍生物，其化学式为(I)1，其中每个符号如规范中所定义，具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP1308439B1

  公开（公告）日：2008-10-15
• US7060722B2
  申请人：——

  公开号：US7060722B2

  公开（公告）日：2006-06-13
• US7074794B2
  申请人：——

  公开号：US7074794B2

  公开（公告）日：2006-07-11