(S)-2-(2,4-dioxotetrahydropyrimidin-1-yl)-3-methylbutyric acid tert-butyl ester | 192725-88-5

• 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: (S)-2-(2,4-dioxotetrahydropyrimidin-1-yl)-3-methylbutyric acid tert-butyl ester
• 英文别名: 2S-(1-Tetrahydro-pyrimid-2,4-dionyl)-3-methylbutanoic acid t-butyl ester；1,1-Dimethylethyl (I+/-S)-tetrahydro-I+/--(1-methylethyl)-2,4-dioxo-1(2H)-pyrimidineacetate；tert-butyl (2S)-2-(2,4-dioxo-1,3-diazinan-1-yl)-3-methylbutanoate
• CAS: 192725-88-5
• 化学式: C₁₃H₂₂N₂O₄
• 分子量: 270.329
• InChiKey: KWPYNVVPVMJYQO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(2,4-dioxotetrahydropyrimidin-1-yl)-3-methylbutyric acid tert-butyl ester 在 N-甲基吗啉 、 N-羟基丁二酰亚胺 、 sodium hexamethyldisilazane 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (S)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(4-hydroxybenzenesulfonyl)isobutylamino]propyl}-2-[3-(2-ethylthiazol-4-ylmethyl)-2,4-dioxotetrahydropyrimidin-1-yl]-3-methylbutyramide
  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：

  (S)-2-(2-Carboxy-ethylamino)-3-methyl-butyric acid tert-butyl ester 在 吡啶 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-(2,4-dioxotetrahydropyrimidin-1-yl)-3-methylbutyric acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir)

  摘要：

  The HIV protease inhibitor ABT-378 (Lopinavir) is metabolized rapidly and extensively by CYP-3A4 catalyzed oxidation. Three of the major metabolites identified were synthesized and their antiviral (HIV) activities determined. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00243-8

文献信息

• Retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：EP1170289A2

  公开（公告）日：2002-01-09

  A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.

  披露了一种包含公式（II）取代基的化合物，作为一种HIV蛋白酶抑制剂。还披露了用于制造此类化合物的中间体以及制造此类中间体的过程。