3-(piperidin-4-yl)isoxazol-5(2H)-one | 1028271-43-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(piperidin-4-yl)isoxazol-5(2H)-one
• 英文别名: 3-(Piperidin-4-yl)isoxazol-5-ol；3-piperidin-4-yl-2H-1,2-oxazol-5-one
• CAS: 1028271-43-3
• 化学式: C₈H₁₂N₂O₂
• 分子量: 168.195
• InChiKey: OSMZMMPRYUBKJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(piperidin-4-yl)isoxazol-5(2H)-one 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以333 mg的产率得到3-(piperidin-4-yl)isoxazol-5(2H)-one hydrochloride
  参考文献：
  名称：

  Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

  摘要：

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

  DOI：

  10.1021/ml400526d
• 作为产物：
  描述：

  N-BOC-4-(2-乙氧羰基乙酰基)哌啶 在 盐酸 、 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 17.5h， 生成 3-(piperidin-4-yl)isoxazol-5(2H)-one
  参考文献：
  名称：

  Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

  摘要：

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

  DOI：

  10.1021/ml400526d

文献信息

• Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction
  作者：Leifeng Cheng、Daniel Pettersen、Bengt Ohlsson、Peter Schell、Michael Karle、Emma Evertsson、Sara Pahlén、Maria Jonforsen、Alleyn T. Plowright、Jonas Boström、Tomas Fex、Anders Thelin、Constanze Hilgendorf、Yafeng Xue、Göran Wahlund、Walter Lindberg、Lars-Olof Larsson、David Gustafsson

  DOI：10.1021/ml400526d

  日期：2014.5.8

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.