potassium 4-(4-fluorobenzylcarbamoyl)-6-methoxy-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)pyrimidin-5-olate | 1370588-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: potassium 4-(4-fluorobenzylcarbamoyl)-6-methoxy-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)pyrimidin-5-olate
• 英文别名: N-[1-[4-[(4-fluorophenyl)methylcarbamoyl]-5-hydroxy-6-methoxy-pyrimidin-2-yl]-1-methyl-ethyl]-5-methyl-1,3,4-oxadiazole-2-carboxamide；potassium;4-[(4-fluorophenyl)methylcarbamoyl]-6-methoxy-2-[2-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]propan-2-yl]pyrimidin-5-olate
• CAS: 1370588-49-0
• 化学式: C₂₀H₂₀FN₆O₅*K
• 分子量: 482.513
• InChiKey: LPULCHSWVMGQBN-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.01
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate 在 potassium tert-butylate 、 magnesium methanolate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 9.0h， 生成 potassium 4-(4-fluorobenzylcarbamoyl)-6-methoxy-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)pyrimidin-5-olate
  参考文献：
  名称：

  Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance

  摘要：

  Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC-MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium.

  DOI：

  10.1021/op300077m

文献信息

• Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors
  作者：Ziwen Wang、Mingxiao Wang、Xue Yao、Yue Li、Wentao Qiao、Yunqi Geng、Yuxiu Liu、Qingmin Wang

  DOI：10.1016/j.ejmech.2012.02.015

  日期：2012.4

  A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC50 values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors. (C) 2012 Elsevier Masson SAS. All rights reserved.