(3S,4R)-2-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidyl)-5,7-dimethoxy-4H-1-benzopyran-4-one | 199589-15-6

• 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-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidyl)-5,7-dimethoxy-4H-1-benzopyran-4-one
• 英文别名: cis-(-)-2-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidinyl)-5,7-dimethoxy-4H-1-benzopyran-4-one；2-ethylsulfanyl-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-5,7-dimethoxychromen-4-one
• CAS: 199589-15-6
• 化学式: C₁₉H₂₅NO₅S
• 分子量: 379.477
• InChiKey: ZZFLCTAUPAKZBF-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  93.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,4R)-2-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidyl)-5,7-dimethoxy-4H-1-benzopyran-4-one 在 三溴化硼 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 8.0h， 生成 2-[(2-chlorophenyl)sulfanyl]-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：

  (3S,4R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶醇 在 三氟化硼乙醚 、 caesium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 (3S,4R)-2-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidyl)-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

• 2-thio or 2-oxo flavopiridol analogs
  申请人：Bristol-Myers Squibb Co.

  公开号：US05849733A1

  公开（公告）日：1998-12-15

  Compounds of the formula I ##STR1## and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, m and n are as defined in the disclosure. The compounds of formula I are protein kinase inhibitors and are useful in the treatment of proliferative diseases.

  式I的化合物及其药学上可接受的盐，其中X，R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5，R.sup.6，m和n如本文所定义。式I的化合物是蛋白激酶抑制剂，可用于治疗增生性疾病。
• [EN] 2-THIO OR 2-OXO FLAVOPIRIDOL ANALOGS<br/>[FR] ANALOGUES DE 2-THIO OU 2-OXO FLAVOPIRIDOL
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1997042949A1

  公开（公告）日：1997-11-20

  (EN) 2-Thio or -oxo flavopirdol analogs of formula (I), which are protein kinase inhibitors and are useful in the treatment of proliferative diseases.(FR) Analogues de 2-thio ou 2-oxo flavopiridol représentés par la formule (I), ces analogues sont des inhibiteurs de la protéine kinase et sont utiles dans le traitement de maladies prolifératives.

  (中) 针对第(I)式的一种类物₂-SO-或₂-Oxo-Flavopirdol,它们是蛋白激酶抑制剂,且对治疗分散性疾病有用途。
• 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.