4-((4-fluorobenzyl)carbamoyl)-1-methyl-2-(2-((5-methyl-1,3,4-oxadiazol-2-yl)carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate | 1172131-68-8

• 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: 4-((4-fluorobenzyl)carbamoyl)-1-methyl-2-(2-((5-methyl-1,3,4-oxadiazol-2-yl)carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate
• 英文别名: 4-(4-fluorobenzylcarbamoyl)-1-methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate；[4-[(4-Fluorophenyl)methylcarbamoyl]-1-methyl-2-[1-methyl-1-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]ethyl]-6-oxo-pyrimidin-5-yl] benzoate；[4-[(4-fluorophenyl)methylcarbamoyl]-1-methyl-2-[2-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]propan-2-yl]-6-oxopyrimidin-5-yl] benzoate
• CAS: 1172131-68-8
• 化学式: C₂₇H₂₅FN₆O₆
• 分子量: 548.531
• InChiKey: HCIGKQQOOLBMBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  methyl 5-(benzoyloxy)-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate 在 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 4-((4-fluorobenzyl)carbamoyl)-1-methyl-2-(2-((5-methyl-1,3,4-oxadiazol-2-yl)carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate
  参考文献：
  名称：

  Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.02.015

文献信息

• 一种嘧啶酮酰胺类化合物的制备方法
  申请人：天津国际生物医药联合研究院

  公开号：CN108610338A

  公开（公告）日：2018-10-02

  本发明公开了一种嘧啶酮酰胺类化合物及其制备方法，以嘧啶酮化合物为起始原料，经过四步化学转化得到TN‑A005及其类似物，中间体可以使用甲基四氮唑制备得到，整个制备过程中用到了一锅法投料并且每一步的后处理纯化为重结晶或分散洗涤，避免了使用硅胶柱层析等手段，极大地简化了制备工艺以及提高了制备效率，且总收率可达50％。该方法不仅制备步骤简便，还能提高制备效率。
• US9107922B2
  申请人：——

  公开号：US9107922B2

  公开（公告）日：2015-08-18
• [EN] NOVEL PYRIMIDINECARBOXAMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS PYRIMIDINECARBOXAMIDE
  申请人：CONCERT PHARMACEUTICALS INC

  公开号：WO2012009446A1

  公开（公告）日：2012-01-19

  This disclosure relates to novel HIV integrase inhibitors their derivatives, pharmaceutically acceptable salts thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating HIV infections.
• 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.