L-Valine, N-[[[(1S)-1-[[(3a'R,6a'S)-1'-(cyclopropylcarbonyl)hexahydro-2'-oxospiro[cyclobutane-1,3'(4'H)-pyrrolo[3,2-b]pyrrol]-4'-yl]carbonyl]-2-methylpropyl]amino]carbonyl]-, 1,1-dimethylethyl ester | 640294-73-1

• 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: L-Valine, N-[[[(1S)-1-[[(3a'R,6a'S)-1'-(cyclopropylcarbonyl)hexahydro-2'-oxospiro[cyclobutane-1,3'(4'H)-pyrrolo[3,2-b]pyrrol]-4'-yl]carbonyl]-2-methylpropyl]amino]carbonyl]-, 1,1-dimethylethyl ester
• 英文别名: tert-butyl (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-methylbutanoate
• CAS: 640294-73-1
• 化学式: C₂₈H₄₄N₄O₆
• 分子量: 532.681
• InChiKey: ZVJWVKCPVWDZLN-TUFLPTIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-Valine, N-[[[(1S)-1-[[(3a'R,6a'S)-1'-(cyclopropylcarbonyl)hexahydro-2'-oxospiro[cyclobutane-1,3'(4'H)-pyrrolo[3,2-b]pyrrol]-4'-yl]carbonyl]-2-methylpropyl]amino]carbonyl]-, 1,1-dimethylethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 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. 5. Pharmacokinetic Optimization of Inhibitors of Hepatitis C Virus NS3/4A Protease

  摘要：

  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.

  DOI：

  10.1021/ol035827n
• 作为产物：
  描述：

  (3aS,6aR)-1-[(2S)-2-amino-3-methylbutanoyl]-4-(cyclopropanecarbonyl)spiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-5-one 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 L-Valine, N-[[[(1S)-1-[[(3a'R,6a'S)-1'-(cyclopropylcarbonyl)hexahydro-2'-oxospiro[cyclobutane-1,3'(4'H)-pyrrolo[3,2-b]pyrrol]-4'-yl]carbonyl]-2-methylpropyl]amino]carbonyl]-, 1,1-dimethylethyl ester
  参考文献：
  名称：

  Pyrrolidine-5,5-trans-lactams. 5. Pharmacokinetic Optimization of Inhibitors of Hepatitis C Virus NS3/4A Protease

  摘要：

  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.

  DOI：

  10.1021/ol035827n

文献信息

• Pyrrolidine-5,5-<i>trans</i>-lactams. 4. Incorporation of a P3/P4 Urea Leads to Potent Intracellular Inhibitors of Hepatitis C Virus NS3/4A Protease
  作者：Martin J. Slater、Elizabeth M. Amphlett、David M. Andrews、Paul Bamborough、Seb J. Carey、Martin R. Johnson、Paul S. Jones、Gail Mills、Nigel R. Parry、Donald O'N. Somers,、Alan J. Stewart、Tadeusz Skarzynski

  DOI：10.1021/ol035826v

  日期：2003.11.1

  [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.
• 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.