N-[2-{4-(4-acetylpiperazin-1-yl)phenyl}-7-morpholin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl]-N'-(3-methylbenzylidene)hydrazine trifluoroacetate | 1232223-50-5

• 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-[2-{4-(4-acetylpiperazin-1-yl)phenyl}-7-morpholin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl]-N'-(3-methylbenzylidene)hydrazine trifluoroacetate
• CAS: 1232223-50-5
• 化学式: C₂HF₃O₂*C₃₀H₃₄N₈O₂
• 分子量: 652.676
• InChiKey: AHQKXYDZWGOTHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  47.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  127.9
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  N-[2-{4-(4-(t-butoxycarbonyl)piperazin-1-yl)phenyl}-7-morpholin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl]-N'-(3-methylbenzylidene)hydrazine 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.33h， 生成 N-[2-{4-(4-acetylpiperazin-1-yl)phenyl}-7-morpholin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl]-N'-(3-methylbenzylidene)hydrazine trifluoroacetate
  参考文献：
  名称：

  PYRAZOLO-PYRIMIDINE COMPOUNDS

  摘要：

  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。

  公开号：

  US20110294781A1

文献信息

• Structure–activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201
  作者：Nobuhiko Hayakawa、Masatsugu Noguchi、Sen Takeshita、Agung Eviryanti、Yukie Seki、Hikaru Nishio、Ryohei Yokoyama、Misato Noguchi、Manami Shuto、Yoichiro Shima、Kanna Kuribayashi、Shunsuke Kageyama、Hiroyuki Eda、Manabu Suzuki、Tomohisa Hatta、Shun-ichiro Iemura、Tohru Natsume、Itsuya Tanabe、Ryusuke Nakagawa、Makoto Shiozaki、Kuniya Sakurai、Masataka Shoji、Ayatoshi Andou、Takashi Yamamoto

  DOI：10.1016/j.bmc.2014.03.036

  日期：2014.6

  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.