N-(2-methylphenyl)-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-9-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-methylphenyl)-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-9-carboxamide
• 英文别名: N-(2-methylphenyl)-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidine-9-carboxamide
• 化学式: C₂₀H₂₀N₄O₃
• 分子量: 364.404
• InChiKey: QSHSDGGNXASYGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-9-carboxylate 在 2,6-二甲基吡啶 、 氰基磷酸二乙酯 、 甲基磺酰氯 、 三乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N-(2-methylphenyl)-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-9-carboxamide
  参考文献：
  名称：

  Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling

  摘要：

  A novel series of TGX-221 analogues was prepared and tested for their potency against the p110 alpha, p110 beta, and p110 delta isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110 beta comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110 beta-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.073

文献信息

• Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling
  作者：Andrew J. Marshall、Claire L. Lill、Mindy Chao、Sharada V. Kolekar、Woo-Jeong Lee、Elaine S. Marshall、Bruce C. Baguley、Peter R. Shepherd、William A. Denny、Jack U. Flanagan、Gordon W. Rewcastle

  DOI：10.1016/j.bmc.2015.03.073

  日期：2015.7

  A novel series of TGX-221 analogues was prepared and tested for their potency against the p110 alpha, p110 beta, and p110 delta isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110 beta comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110 beta-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution. (C) 2015 Elsevier Ltd. All rights reserved.