5-amino-3-n-butyl-4-cyano-1-(2,4,6-trichlorophenyl)pyrazole | 812668-03-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-3-n-butyl-4-cyano-1-(2,4,6-trichlorophenyl)pyrazole
• 英文别名: 5-Amino-3-butyl-1-(2,4,6-trichlorophenyl)pyrazole-4-carbonitrile
• CAS: 812668-03-4
• 化学式: C₁₄H₁₃Cl₃N₄
• 分子量: 343.643
• InChiKey: AVPKPJKYYAVYCX-UHFFFAOYSA-N

物化性质

• 熔点：
  123-124 °C
• 沸点：
  499.7±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-amino-3-n-butyl-4-cyano-1-(2,4,6-trichlorophenyl)pyrazole 在 硫酸 作用下， 反应 2.5h， 以98%的产率得到5-amino-3-n-butyl-4-carboxamido-1-(2,4,6-trichlorophenyl)pyrazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases

  摘要：

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.

  DOI：

  10.1021/jm020455u
• 作为产物：
  描述：

  原戊酸三甲酯 在 乙酸酐 作用下， 以 甲醇 为溶剂， 反应 17.0h， 生成 5-amino-3-n-butyl-4-cyano-1-(2,4,6-trichlorophenyl)pyrazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases

  摘要：

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.

  DOI：

  10.1021/jm020455u

文献信息

• Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases
  作者：Jay A. Markwalder、Marc R. Arnone、Pamela A. Benfield、Michael Boisclair、Catherine R. Burton、Chong-Hwan Chang、Sarah S. Cox、Philip M. Czerniak、Charity L. Dean、Deborah Doleniak、Robert Grafstrom、Barbara A. Harrison、Robert F. Kaltenbach、David A. Nugiel、Karen A. Rossi、Susan R. Sherk、Lisa M. Sisk、Pieter Stouten、George L. Trainor、Peter Worland、Steven P. Seitz

  DOI：10.1021/jm020455u

  日期：2004.11.1

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.