N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxo-9-(1-phenoxyethyl)pyrido[1,2-a]pyrimidine-7-carboxamide | 1622905-89-8

• 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: N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxo-9-(1-phenoxyethyl)pyrido[1,2-a]pyrimidine-7-carboxamide
• CAS: 1622905-89-8
• 化学式: C₂₄H₂₈N₄O₅
• 分子量: 452.51
• InChiKey: IEYLWEAQUDHMKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  94.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxo-9-(1-phenoxyethyl)pyrido[1,2-a]pyrimidine-7-carboxamide 在 Chiralpak AD column 作用下， 生成 N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxo-9-[(1R)-1-phenoxyethyl]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：

  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 、 三苯基膦 、 三氟乙酸 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 16.25h， 生成 N-(2-hydroxyethyl)-N-methyl-2-morpholin-4-yl-4-oxo-9-(1-phenoxyethyl)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