3-methyl-2-(2-oxo-2,3-dihydroimidazol-1-yl)butyric acid | 911067-20-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-methyl-2-(2-oxo-2,3-dihydroimidazol-1-yl)butyric acid
• 英文别名: (2S)-3-methyl-2-(2-oxo-1H-imidazol-3-yl)butanoic acid
• CAS: 911067-20-4
• 化学式: C₈H₁₂N₂O₃
• 分子量: 184.195
• InChiKey: SPQBFHFXWVTRNJ-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-2-(2-oxo-2,3-dihydroimidazol-1-yl)butyric acid 、 N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide 在 3-dimethoxyphosphoryloxy-1,2,3-benzotriazine-4(3H)-one 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以24%的产率得到(S)-N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-(4-methoxy-benzenesulfonyl)-amino]-propyl}-3-methyl-2-(2-oxo-2,3-dihydro-imidazol-1-yl)-butyramide
  参考文献：
  名称：

  Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV

  摘要：

  A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity versus wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in NIT-4 cells). Select imidazolidine-2,4-dione containing Pis were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 mu g h/mL. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.063
• 作为产物：
  描述：

  N-[[(4-nitrophenyl)oxy]carbonyl]-L-valine methyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide 、 甲酸 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 51.0h， 生成 3-methyl-2-(2-oxo-2,3-dihydroimidazol-1-yl)butyric acid
  参考文献：
  名称：

  Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV

  摘要：

  A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity versus wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in NIT-4 cells). Select imidazolidine-2,4-dione containing Pis were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 mu g h/mL. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.063