(3S,4R)-2-(2-chlorophenyl)-8-(3-hydroxy-1-methyl-4-piperidinyl)-5,7-dimethoxy-4H-1-benzopyran-4-one | 199589-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,4R)-2-(2-chlorophenyl)-8-(3-hydroxy-1-methyl-4-piperidinyl)-5,7-dimethoxy-4H-1-benzopyran-4-one
• 英文别名: 2-(2-chlorophenoxy)-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-5,7-dimethoxychromen-4-one
• CAS: 199589-13-4
• 化学式: C₂₃H₂₄ClNO₆
• 分子量: 445.9
• InChiKey: BTGDOTFSTDOBED-XJKSGUPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,4R)-2-(2-chlorophenyl)-8-(3-hydroxy-1-methyl-4-piperidinyl)-5,7-dimethoxy-4H-1-benzopyran-4-one 在 三溴化硼 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 2-(2-chlorophenoxy)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-chromen-4-one
  参考文献：
  名称：

  Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects

  摘要：

  Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC50 Of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

  DOI：

  10.1021/jm000231g
• 作为产物：
  描述：

  8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-5,7-dimethoxy-2-sulfanylchromen-4-one 在 caesium carbonate 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 (3S,4R)-2-(2-chlorophenyl)-8-(3-hydroxy-1-methyl-4-piperidinyl)-5,7-dimethoxy-4H-1-benzopyran-4-one
  参考文献：
  名称：

  Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects

  摘要：

  Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC50 Of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

  DOI：

  10.1021/jm000231g

文献信息

• US5849733A
  申请人：——

  公开号：US5849733A

  公开（公告）日：1998-12-15
• Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects
  作者：Kyoung Soon Kim、John S. Sack、John S. Tokarski、Ligang Qian、Sam T. Chao、Leslie Leith、Yolanda F. Kelly、Raj N. Misra、John T. Hunt、S. David Kimball、William G. Humphreys、Barris S. Wautlet、Janet G. Mulheron、Kevin R. Webster

  DOI：10.1021/jm000231g

  日期：2000.11.1

  Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC50 Of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.