4-(3-Thiophen-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one | 408502-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-(3-Thiophen-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one
• 英文别名: 4-(3-thiophen-3-ylpyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one
• CAS: 408502-25-0
• 化学式: C₁₅H₁₀N₄OS
• 分子量: 294.337
• InChiKey: YMXXSVFGZWAQAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-氯丙基)-4-甲基哌嗪 、 4-(3-Thiophen-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one 在 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到1-[3-(4-methylpiperazin-1-yl)-propyl]-4-(3-thiophen-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one
  参考文献：
  名称：

  Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics

  摘要：

  We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.(C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00827-2
• 作为产物：
  描述：

  2-甲氧基-吡啶 1-氧化物 在 硫酸 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 硫酸 、 硝酸 、 potassium acetate 、 吡啶盐酸盐 、 铁粉 、 sodium carbonate 、 copper(II) sulfate 、 溶剂黄146 、 sodium bromide 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(3-Thiophen-3-yl-pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyridin-2-one
  参考文献：
  名称：

  Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics

  摘要：

  We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.(C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00827-2

文献信息

• Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics
  作者：Mark E. Fraley、Robert S. Rubino、William F. Hoffman、Scott R. Hambaugh、Kenneth L. Arrington、Randall W. Hungate、Mark T. Bilodeau、Andrew J. Tebben、Ruth Z. Rutledge、Richard L. Kendall、Rosemary C. McFall、William R. Huckle、Kathleen E. Coll、Kenneth A. Thomas

  DOI：10.1016/s0960-894x(02)00827-2

  日期：2002.12

  We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.(C) 2002 Elsevier Science Ltd. All rights reserved.