4-(4-(pyridin-4-ylmethyl)piperazin-1-yl)quinolin-6-ylboronic acid | 1312448-30-8

• 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-(4-(pyridin-4-ylmethyl)piperazin-1-yl)quinolin-6-ylboronic acid
• 英文别名: [4-[4-(Pyridin-4-ylmethyl)piperazin-1-yl]quinolin-6-yl]boronic acid
• CAS: 1312448-30-8
• 化学式: C₁₉H₂₁BN₄O₂
• 分子量: 348.212
• InChiKey: MYJANHDDMIURFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.63
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide 、 4-(4-(pyridin-4-ylmethyl)piperazin-1-yl)quinolin-6-ylboronic acid 以51%的产率得到N-(2-chloro-5-(4-(4-(pyridin-4-ylmethyl)piperazin-1-yl)quinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide
  参考文献：
  名称：

  Phospshoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Discovery and Structure–Activity Relationships of a Series of Quinoline and Quinoxaline Derivatives

  摘要：

  The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3'-hydroxyl group of phosphatidylinositols and plays an important role in cell growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.

  DOI：

  10.1021/jm200386s
• 作为产物：
  描述：

  6-溴-4-氯喹啉 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(4-(pyridin-4-ylmethyl)piperazin-1-yl)quinolin-6-ylboronic acid
  参考文献：
  名称：

  Phospshoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Discovery and Structure–Activity Relationships of a Series of Quinoline and Quinoxaline Derivatives

  摘要：

  The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3'-hydroxyl group of phosphatidylinositols and plays an important role in cell growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.

  DOI：

  10.1021/jm200386s

文献信息

• Phospshoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Discovery and Structure–Activity Relationships of a Series of Quinoline and Quinoxaline Derivatives
  作者：Nobuko Nishimura、Aaron Siegmund、Longbin Liu、Kevin Yang、Marian C. Bryan、Kristin L. Andrews、Yunxin Bo、Shon K. Booker、Sean Caenepeel、Daniel Freeman、Hongyu Liao、John McCarter、Erin L. Mullady、Tisha San Miguel、Raju Subramanian、Nuria Tamayo、Ling Wang、Douglas A. Whittington、Leeanne Zalameda、Nancy Zhang、Paul E. Hughes、Mark H. Norman

  DOI：10.1021/jm200386s

  日期：2011.7.14

  The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3'-hydroxyl group of phosphatidylinositols and plays an important role in cell growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.