6-(2-Methoxypyridin-4-yl)-3-thiophen-3-yl-pyrazolo[1-5-a]pyrimidine | 408502-24-9

• 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: 6-(2-Methoxypyridin-4-yl)-3-thiophen-3-yl-pyrazolo[1-5-a]pyrimidine
• 英文别名: 6-(2-Methoxy-4-pyridinyl)-3-(3-thienyl)pyrazolo[1,5-a]pyrimidine；6-(2-methoxypyridin-4-yl)-3-thiophen-3-ylpyrazolo[1,5-a]pyrimidine
• CAS: 408502-24-9
• 化学式: C₁₆H₁₂N₄OS
• 分子量: 308.363
• InChiKey: PRVNBTLLMGCLLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2-Methoxypyridin-4-yl)-3-thiophen-3-yl-pyrazolo[1-5-a]pyrimidine 在 吡啶盐酸盐 作用下， 以93%的产率得到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 、 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 6-(2-Methoxypyridin-4-yl)-3-thiophen-3-yl-pyrazolo[1-5-a]pyrimidine
  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

• Method of treating cancer
  申请人：——

  公开号：US20020041880A1

  公开（公告）日：2002-04-11

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of angiogenesis, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of angiogenesis. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA结合物和一种抑制血管生成的化合物的组合治疗癌症的方法，该方法包括向所述哺乳动物施用至少两种治疗剂量，这些治疗剂量选自一组化合物，其中一种是PSA结合物，另一种是抑制血管生成的化合物，这些治疗剂量可以顺序给药或同时给药，本发明还涉及制备这种组合物的方法。
• 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.