N-(3-methylbenzylidene)-N'-{7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidin-5-yl}hydrazine trifluoroacetate | 1232223-47-0

• 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: N-(3-methylbenzylidene)-N'-{7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidin-5-yl}hydrazine trifluoroacetate
• CAS: 1232223-47-0
• 化学式: C₂HF₃O₂*C₂₈H₃₂N₈O
• 分子量: 610.639
• InChiKey: SXHMGTBIPJNOCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  44.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  119.62
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-(3-methylbenzylidene)-N'-{7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidin-5-yl}hydrazine trifluoroacetate 、 戊酰氯 以 二氯甲烷 为溶剂， 反应 2.0h， 以27.2 mg的产率得到N-(3-methyl-benzylidene)-N'-{7-morpholin-4-yl-2-[4-(1-oxo-pentan-1-yl)piperazin-1-yl-phenyl]pyrazolo[1,5-a]pyrimidin-5-yl}hydrazine 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
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.33h， 生成 N-(3-methylbenzylidene)-N'-{7-morpholin-4-yl-2-(4-piperazin-1-yl-phenyl)pyrazolo[1,5-a]pyrimidin-5-yl}hydrazine 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

文献信息

• PYRAZOLO-PYRIMIDINE COMPOUNDS
  申请人：YAMAMOTO Takashi

  公开号：US20110294781A1

  公开（公告）日：2011-12-01

  The present invention has searched for a variety of compounds which show IL-12/IL-23 production-inhibitory activities and herein provides a pharmaceutical composition and an agent for preventing or treating IL-12/IL-23 excess production-related diseases, which comprise the compound.

  本发明已经寻找到多种显示IL-12/IL-23产生抑制活性的化合物，并在此提供了包括该化合物的用于预防或治疗IL-12/IL-23过度产生相关疾病的药物组合物和药剂。