2,4-difluoro-N-(2-methoxy-5-(4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide | 1148008-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,4-difluoro-N-(2-methoxy-5-(4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide
• 英文别名: 2,4-difluoro-N-[2-(methyloxy)-5-(4-oxo-3-phenyl-3,4-dihydro-6-quinazolinyl)-3-pyridinyl]benzenesulfonamide；2,4-difluoro-N-[2-methoxy-5-(4-oxo-3-phenylquinazolin-6-yl)pyridin-3-yl]benzenesulfonamide
• CAS: 1148008-69-8
• 化学式: C₂₆H₁₈F₂N₄O₄S
• 分子量: 520.516
• InChiKey: TZSMYZUYCXMTAV-UHFFFAOYSA-N

物化性质

• 沸点：
  706.3±70.0 °C(predicted)
• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 6.5h， 生成 2,4-difluoro-N-(2-methoxy-5-(4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds

  摘要：

  In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIII alpha is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIII alpha inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.

  DOI：

  10.1021/acsmedchemlett.6b00232

文献信息

• [EN] PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDOSULFONAMIDE EN TANT QU'INHIBITEURS DE PI3 KINASE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009055418A1

  公开（公告）日：2009-04-30

  Invented is a method of inhibiting the activity/function of PB kinases using pyridosulfonamide derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of pyridosulfonamide derivatives.

  发明了一种使用吡啶磺酰胺衍生物抑制PB激酶活性/功能的方法。还发明了一种通过给予吡啶磺酰胺衍生物来治疗自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官功能衰竭、肾脏疾病、血小板聚集、癌症、精子活动力、移植排斥、移植物排斥和肺部损伤等一种或多种疾病状态的方法。
• PYRIDOSULFONAMIDE DERIVATIVES AS P13 KINASE INHIBITORS
  申请人：Adams Nicholas D.

  公开号：US20100311736A1

  公开（公告）日：2010-12-09

  Invented is a method of inhibiting the activity/function of PI3 kinases using pyridosulfonamide derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of pyridosulfonamide derivatives.

  本发明涉及使用吡啶磺酰胺衍生物抑制PI3激酶的活性/功能的方法。本发明还涉及使用吡啶磺酰胺衍生物治疗自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺损伤的方法。
• METHODS FOR OLIGOMERIZING OLEFINS
  申请人：ExxonMobil Chemical Patents Inc.

  公开号：EP1856010B1

  公开（公告）日：2010-07-28
• PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：EP2211615A1

  公开（公告）日：2010-08-04
• Concise SAR Exploration Based on the “Head-to-Tail” Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds
  作者：Satoru Noji、Noriyoshi Seki、Takaki Maeba、Takayuki Sakai、Eiichi Watanabe、Katsuya Maeda、Kyoko Fukushima、Toru Noguchi、Kazuya Ogawa、Yukiyo Toyonaga、Tamotsu Negoro、Hisashi Kawasaki、Makoto Shiozaki

  DOI：10.1021/acsmedchemlett.6b00232

  日期：2016.10.13

  In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIII alpha is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIII alpha inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.