9-acetyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid | 1622880-51-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 9-acetyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid
• CAS: 1622880-51-6
• 化学式: C₁₅H₁₅N₃O₅
• 分子量: 317.301
• InChiKey: GNQYCZNVLGQVFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.43
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101.21
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  9-acetyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid 在 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 、 O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.25h， 生成 N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-9-(1-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxamide
  参考文献：
  名称：

  Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents

  摘要：

  Optimization of AZD6482 (2), the first antiplatelet PI3K beta inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3K alpha to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3K beta inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.07.007
• 作为产物：
  描述：

  在 盐酸 、 1,3-双(二苯基膦)丙烷 、 palladium diacetate 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 9-acetyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid
  参考文献：
  名称：

  Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents

  摘要：

  Optimization of AZD6482 (2), the first antiplatelet PI3K beta inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3K alpha to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3K beta inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.07.007

文献信息

• Discovery of 9-(1-anilinoethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours
  作者：Bernard Barlaam、Sabina Cosulich、Sébastien Degorce、Martina Fitzek、Fabrizio Giordanetto、Stephen Green、Tord Inghardt、Laurent Hennequin、Urs Hancox、Christine Lambert-van der Brempt、Rémy Morgentin、Sarah Pass、Patrick Plé、Twana Saleh、Lara Ward

  DOI：10.1016/j.bmcl.2014.06.040

  日期：2014.8

  Starting from TGX-221, we designed a series of 9-(1-anilinoethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as potent and selective PI3Kβ/δ inhibitors. Structure-activity relationships and structure-property relationships around the aniline and the amide substituents are discussed. We identified compounds 17 and 18, which showed profound pharmacodynamic modulation of phosphorylated Akt in the PC3 prostate tumour xenograft, after a single oral dose. Compound 17 also gave significant inhibition of tumour growth in the PC3 prostate tumour xenograft model after chronic oral dosing.