tert-butyl (2S)-2-[[(2S)-1-[(3'aS,6'aS)-4'-(2-methylpropanoyl)-5'-oxospiro[1,3-dithiolane-2,6'-2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole]-1'-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoate | 1054655-28-5

• 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: tert-butyl (2S)-2-[[(2S)-1-[(3'aS,6'aS)-4'-(2-methylpropanoyl)-5'-oxospiro[1,3-dithiolane-2,6'-2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole]-1'-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoate
• CAS: 1054655-28-5
• 化学式: C₂₇H₄₄N₄O₆S₂
• 分子量: 584.802
• InChiKey: IWTDIUOYEQOYQK-MUGJNUQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[[(2S)-1-[(3'aS,6'aS)-4'-(2-methylpropanoyl)-5'-oxospiro[1,3-dithiolane-2,6'-2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole]-1'-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoate 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 1-[(2S)-1-[(3'aS,6'aS)-4'-(2-methylpropanoyl)-5'-oxospiro[1,3-dithiolane-2,6'-2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole]-1'-yl]-3-methyl-1-oxobutan-2-yl]-3-[(2S)-3-methyl-1-oxo-1-(4-pyrimidin-2-ylpiperazin-1-yl)butan-2-yl]urea
  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：

  在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl (2S)-2-[[(2S)-1-[(3'aS,6'aS)-4'-(2-methylpropanoyl)-5'-oxospiro[1,3-dithiolane-2,6'-2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole]-1'-yl]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoate
  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. 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.