5-amino-4-carboxamido-3-(methylthio)-1-(2,4,6-trimethylphenyl)pyrazole | 812667-79-1

• 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-4-carboxamido-3-(methylthio)-1-(2,4,6-trimethylphenyl)pyrazole
• 英文别名: 5-amino-3-methylsulfanyl-1-(2,4,6-trimethylphenyl)-1H-pyrazole-4-carboxamide；5-Amino-3-methylsulfanyl-1-(2,4,6-trimethylphenyl)pyrazole-4-carboxamide
• CAS: 812667-79-1
• 化学式: C₁₄H₁₈N₄OS
• 分子量: 290.389
• InChiKey: WUWWUSJUJAOHQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酸乙酯 、 5-amino-4-carboxamido-3-(methylthio)-1-(2,4,6-trimethylphenyl)pyrazole 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以66%的产率得到Pyrazolo[3,4-d]pyrimidin-4-one deriv. 4x
  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：

  异丙叉肼 生成 5-amino-4-carboxamido-3-(methylthio)-1-(2,4,6-trimethylphenyl)pyrazole
  参考文献：
  名称：

  Pyrazolopyrimidines as CRF antagonists

  摘要：

  以下为该化合物的中文翻译及其药用酸盐： 该化合物的化学式为：其中A为NR1R2、CR1R2R11、或C(═CR1R12)R2、NHCR1R2R11、OCR1R2R11、SCR1R2R11、NHNR1R2、CR2R11NHR1、CR2R11OR1、CR2R11SR1或C(O)R2；其中其余变量定义如下，用于治疗炎症性疾病。

  公开号：

  US06218397B1

文献信息

• PYRAZOLOPYRIMIDINES AS CRF ANTAGONISTS
  申请人：PFIZER INC.

  公开号：EP0674642B1

  公开（公告）日：2000-08-23
• US6218397B1
  申请人：——

  公开号：US6218397B1

  公开（公告）日：2001-04-17
• [EN] PYRAZOLOPYRIMIDINES AS CRF ANTAGONISTS<br/>[FR] PYRAZOLOPYRIMIDINES EMPLOYES COMME ANTAGONISTES DU FACTEUR DE LIBERATION DE CORTICOTROPINE
  申请人：——

  公开号：WO1994013677A1

  公开（公告）日：1994-06-23

  [EN] Corticotropin-releasing factor (CRF) antagonists have formula (I), wherein A, R3, R4 and R5 are as defined herein. They are useful in the treatment of illnesses induced or facilitated by CRF, such as inflammatory disorders, and depression and anxiety related disorders.
  [FR] Antagonistes du facteur de libération de corticotropine, de la formule (I) dans laquelle A, R3, R4 et R5 sont tels que définis dans la demande. Ces antagonistes sont utiles pour le traitement des maladies induites ou facilitées par le facteur sus-mentionné, telles que les maladies inflammatoires, ainsi que les troubles liés à la dépression et à l'anxiété.