N-cyclopropyl-3-(1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ylamino)-4-methylbenzamide | 1148050-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-cyclopropyl-3-(1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ylamino)-4-methylbenzamide
• 英文别名: N-cyclopropyl-3-{[1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-4-methylbenzamide；N-cyclopropyl-3-[[1-(2,4-difluorophenyl)-7-methyl-6-oxopyrazolo[3,4-b]pyridin-4-yl]amino]-4-methylbenzamide
• CAS: 1148050-90-1
• 化学式: C₂₄H₂₁F₂N₅O₂
• 分子量: 449.46
• InChiKey: WMEYCLAVMZKZCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氨基-N-环丙基-4-甲基苯甲酰胺 、 4-chloro-1-(2,4-difluorophenyl)-7-methylpyrazolo[3,4-b]pyridin-6-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 N-cyclopropyl-3-(1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ylamino)-4-methylbenzamide
  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

文献信息

• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.