(2S)-2-[[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoic acid | 640294-77-5

• 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: (2S)-2-[[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoic acid
• CAS: 640294-77-5
• 化学式: C₂₄H₃₆N₄O₆
• 分子量: 476.573
• InChiKey: FOQBFJJSRVAFGK-XSLAGTTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-嘧啶基)哌嗪 、 (2S)-2-[[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙腈 为溶剂， 生成 1-[(1S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxo-spiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-carbonyl]-2-methyl-propyl]-3-[(1S)-2-methyl-1-(4-pyrimidin-2-ylpiperazine-1-carbonyl)propyl]urea
  参考文献：
  名称：

  Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 Urea Leads to Potent Intracellular Inhibitors of Hepatitis C Virus NS3/4A Protease

  摘要：

  [reaction: see text] In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC(50) in the replicon cell-based surrogate HCV assay.

  DOI：

  10.1021/ol035826v
• 作为产物：
  描述：

  L-缬氨酸苄酯 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 (2S)-2-[[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoic acid
  参考文献：
  名称：

  Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 Urea Leads to Potent Intracellular Inhibitors of Hepatitis C Virus NS3/4A Protease

  摘要：

  [reaction: see text] In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC(50) in the replicon cell-based surrogate HCV assay.

  DOI：

  10.1021/ol035826v

文献信息

• Pyrrolidine-5,5-<i>trans</i>-lactams. 5. Pharmacokinetic Optimization of Inhibitors of Hepatitis C Virus NS3/4A Protease
  作者：David M. Andrews、Michael C. Barnes、Mike D. Dowle、S. Lucy Hind、Martin R. Johnson、Paul S. Jones、Gail Mills、Angela Patikis、Tony J. Pateman、Tracy J. Redfern、J. Ed Robinson、Martin J. Slater、Naimisha Trivedi

  DOI：10.1021/ol035827n

  日期：2003.11.1

  In this, the second of two Letters, the optimization of the pyrrolidine-5,5-trans-lactam template (exemplified by 1a) as a mechanism-based inhibitor of hepatitis C NS3/4A protease is described. "Right Box" analysis of cassette dosing screening pharmacokinetic data was used to rapidly categorize the compounds. GW0014 (compound 4d) emerged as the compound displaying an optimal balance of biochemical and replicon potency, along with low i.v. clearance in the dog.