N-(5-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-3-yl)benzenesulfonamide | 1261082-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(5-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-3-yl)benzenesulfonamide
• 英文别名: N-[5-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-3-yl]benzenesulfonamide
• CAS: 1261082-75-0
• 化学式: C₁₈H₁₄N₄O₂S
• 分子量: 350.401
• InChiKey: YXJNCMWPTDBNPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-3-氨基吡啶 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 生成 N-(5-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of new aminopyrimidine-based phosphoinositide 3-kinase beta (PI3Kβ) inhibitors with selectivity over PI3Kα

  摘要：

  Phosphatidylinositol-3-kinase beta (PI3K beta) is an important therapeutic target in arterial thrombosis and special types of cancer. In this study, a new series of aminopyridine-based PI3K beta selective inhibitors have been developed by the structure-based design strategy. When incorporated with the phenyl ring on sulfonamide moiety, aminopyrimidine analogs showed good potency on PI3K beta and selectivity over PI3K alpha. Intriguingly, replacement of phenyl group on sulfonamide with naphthyl group enhanced selectivity over PI3K alpha while retaining submicromolar PI3K beta potency. Molecular modeling suggests that increased PI3K beta specificity is caused by the interaction with salt bridge (Lys782-Asp923) and Asp862 that creat a unique pocket in PI3K beta. These results clearly provide useful insight in the design of new PI3K beta inhibitors with high potency and selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.118

文献信息

• Design and Synthesis of Imidazopyridine Analogues as Inhibitors of Phosphoinositide 3-Kinase Signaling and Angiogenesis
  作者：Okseon Kim、Yujeong Jeong、Hyunseung Lee、Sun-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm101582z

  日期：2011.4.14

  Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives

  磷脂酰肌醇3-激酶α（PI3Kα）是细胞内信号通路的重要调节剂，可控制多种多样的生理过程。由于PI3K途径在人类癌症中经常被上调，因此PI3Kα的抑制可能是一种有前途的癌症治疗方法。在本研究中，我们通过片段增长策略设计并合成了一系列新的咪唑并[1,2- a ]吡啶衍生物作为PI3Kα抑制剂。通过改变咪唑[1,2- a]的3和6位上的基团]吡啶，我们研究了结构活性关系（SAR）谱，并鉴定了一系列有效的PI3Kα抑制剂。代表性衍生物在细胞增殖和凋亡测定中显示出良好的活性。而且，这些抑制剂表现出值得注意的抗血管生成活性。
• Discovery of new azaindole-based PI3Kα inhibitors: Apoptotic and antiangiogenic effect on cancer cells
  作者：Seunghee Hong、Soyoung Lee、Bomi Kim、Hyunseung Lee、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1016/j.bmcl.2010.10.108

  日期：2010.12

  Phosphatidylinositol-3-kinase alpha (PI3K alpha) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3K alpha inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure-activity relationship) and identified a series of potent PI3K alpha inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of new aminopyrimidine-based phosphoinositide 3-kinase beta (PI3Kβ) inhibitors with selectivity over PI3Kα
  作者：Jinhee Kim、Seunghee Hong、Sungwoo Hong

  DOI：10.1016/j.bmcl.2011.09.118

  日期：2011.12

  Phosphatidylinositol-3-kinase beta (PI3K beta) is an important therapeutic target in arterial thrombosis and special types of cancer. In this study, a new series of aminopyridine-based PI3K beta selective inhibitors have been developed by the structure-based design strategy. When incorporated with the phenyl ring on sulfonamide moiety, aminopyrimidine analogs showed good potency on PI3K beta and selectivity over PI3K alpha. Intriguingly, replacement of phenyl group on sulfonamide with naphthyl group enhanced selectivity over PI3K alpha while retaining submicromolar PI3K beta potency. Molecular modeling suggests that increased PI3K beta specificity is caused by the interaction with salt bridge (Lys782-Asp923) and Asp862 that creat a unique pocket in PI3K beta. These results clearly provide useful insight in the design of new PI3K beta inhibitors with high potency and selectivity. (C) 2011 Elsevier Ltd. All rights reserved.