ethyl 5-[acetyl(methyl)amino]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate | 1186491-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-[acetyl(methyl)amino]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate
• 英文别名: Ethyl 5-[acetyl(methyl)amino]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate
• CAS: 1186491-32-6
• 化学式: C₁₅H₁₅F₂N₃O₃
• 分子量: 323.299
• InChiKey: OHIJGKKPYDNSIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.31
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.43
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 5-[acetyl(methyl)amino]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 1-(2,4-difluorophenyl)-4-hydroxy-7-methylpyrazolo[3,4-b]pyridin-6-one
  参考文献：
  名称：

  Part 1: Structure–Activity Relationship (SAR) investigations of fused pyrazoles as potent, selective and orally available inhibitors of p38α mitogen-activated protein kinase

  摘要：

  A novel class of fused pyrazole-derived inhibitors of p38 alpha mitogen-activated protein kinase (MAPK) is disclosed. These inhibitors were evaluated for their ability to inhibit the p38a enzyme, the secretion of TNF alpha in a LPS-challenged THP1 cell line and TNF alpha-induced production of IL-8 in 50% human whole blood. This series was optimized through a SAR investigation to provide inhibitors with IC50 values in the low single-digit nanomolar range in whole blood. Further investigation of their pharmacokinetic profiles led to the identification of two potent and orally bioavailable p38 inhibitors 10m and 10q. Inhibitor 10m was found to be efficacious in vivo in the inhibition of TNFa production in LPS-stimulated Lewis rats with an ED50 of 0.1 mg/kg while 10q was found to have an ED50 of 0.05-0.07 mg/kg. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.058
• 作为产物：
  描述：

  (2,4-二氟苯基)肼盐酸盐(1:1) 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 ethyl 5-[acetyl(methyl)amino]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate
  参考文献：
  名称：

  [EN] IMIDAZOLE MACROCYCLES FOR THE TREATMENT OF AUTOIMMUNE DISEASE
  [FR] MACROCYCLES D'IMIDAZOLE POUR LE TRAITEMENT D'UNE MALADIE AUTO-IMMUNE

  摘要：

  The present invention relates to compounds of formula (Ia), (Ia), wherein R2, M1, M2, M3, Q1and Q2are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

  公开号：

  WO2023148129A1