5-chloro-7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidine trifluoroacetate | 1609492-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-chloro-7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidine trifluoroacetate
• CAS: 1609492-09-2
• 化学式: C₂HF₃O₂*C₂₀H₂₃ClN₆O
• 分子量: 512.919
• InChiKey: FDWQJCZSVRWNMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  35.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  95.23
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 5,8,11,14,17,20-六氧杂-2-氮杂二十三碳二酸 1-(9H-芴-9-基甲基)酯 、 5-chloro-7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidine trifluoroacetate 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 Fmoc-O-叔丁基-L-酪氨酸 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 三氟乙酸 在 N,N-二异丙基乙胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.37h， 生成
  参考文献：
  名称：

  Structure–activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201

  摘要：

  Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. We describe the discovery of APY0201, a unique small molecular IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an experimental model of colitis. Through a chemical proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P-2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.036
• 作为产物：
  描述：

  5-氨基-3-(4-溴苯基)-1H-吡唑 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 sodium ethanolate 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.33h， 生成 5-chloro-7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidine trifluoroacetate
  参考文献：
  名称：

  Structure–activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201

  摘要：

  Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. We describe the discovery of APY0201, a unique small molecular IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an experimental model of colitis. Through a chemical proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P-2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.036