(6-{[4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ6-thiopyran-3-yl]-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionyl]-amino}-hexyl)-carbamic acid tert-butyl ester | 868700-47-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (6-{[4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ6-thiopyran-3-yl]-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionyl]-amino}-hexyl)-carbamic acid tert-butyl ester
• 英文别名: (6-{[4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ⁶-thiopyran-3-yl]-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionyl]-amino}-hexyl)-carbamic acid tert-butyl ester
• CAS: 868700-47-4
• 化学式: C₄₆H₆₅N₃O₈SSi
• 分子量: 848.189
• InChiKey: GNVQSUNCAGOYMZ-GWNAIRJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.63
• 重原子数：
  59.0
• 可旋转键数：
  16.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  140.34
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (6-{[4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ6-thiopyran-3-yl]-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionyl]-amino}-hexyl)-carbamic acid tert-butyl ester 在 哌啶 、 四丁基氟化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 {6-[[(S)-2-((2R,3R)-2-tert-Butoxycarbonylamino-3-methyl-pentanoylamino)-3-phenyl-propionyl]-(4-hydroxy-1,1-dioxo-hexahydro-1λ⁶-thiopyran-3-yl)-amino]-hexyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A Comparison of Cyclohexanone and Tetrahydro-4H-thiopyran-4-one 1,1-Dioxide as Pharmacophores for the Design of Peptide-Based Inhibitors of the Serine Protease Plasmin

  摘要：

  The plasminogen system is important in the proteolytic cascade that facilitates angiogenesis, a process that is essential for tumor growth and metastasis. The serine protease plasmin has a central role in the plasminogen system. This protease acts by degrading several components of the basement membrane and by activating other proteases. Therefore, inhibition of plasmin may be an effective method for blocking angiogenesis and, as a result, inhibiting the growth of primary tumors and secondary metastases. Three pairs of plasmin inhibitors were synthesized to compare the relative potency of inhibitors that are based upon a cyclohexanone or a tetrahydro-4H-thiopyran-4-one 1,1-dioxide nucleus. Compounds 1, 3, and 5 were cyclohexanone-based inhibitors, whereas compounds 2, 4, and 6 were tetrahydro-4H-thiopyran-4-one 1,1-dioxide-based inhibitors. Compounds 5 and 6 are reasonable inhibitors with IC50 values of 25 and 5.5 mu M, respectively. Comparisons of the IC50 values of the three pairs show that the electron-withdrawing sulfone functional group is a beneficial element for the design of plasmin inhibitors. The presence of the sulfone increases inhibitor potency by a factor of 3-5 when compared to inhibitors that are based upon a simple cyclohexanone core.

  DOI：

  10.1021/jo0508954
• 作为产物：
  描述：

  {6-[(E)-(3R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ⁶-thiopyran-3-ylimino]-hexyl}-carbamic acid tert-butyl ester 在 四丁基氟化铵 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 11.0h， 生成 (6-{[4-(tert-Butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ6-thiopyran-3-yl]-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionyl]-amino}-hexyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A Comparison of Cyclohexanone and Tetrahydro-4H-thiopyran-4-one 1,1-Dioxide as Pharmacophores for the Design of Peptide-Based Inhibitors of the Serine Protease Plasmin

  摘要：

  The plasminogen system is important in the proteolytic cascade that facilitates angiogenesis, a process that is essential for tumor growth and metastasis. The serine protease plasmin has a central role in the plasminogen system. This protease acts by degrading several components of the basement membrane and by activating other proteases. Therefore, inhibition of plasmin may be an effective method for blocking angiogenesis and, as a result, inhibiting the growth of primary tumors and secondary metastases. Three pairs of plasmin inhibitors were synthesized to compare the relative potency of inhibitors that are based upon a cyclohexanone or a tetrahydro-4H-thiopyran-4-one 1,1-dioxide nucleus. Compounds 1, 3, and 5 were cyclohexanone-based inhibitors, whereas compounds 2, 4, and 6 were tetrahydro-4H-thiopyran-4-one 1,1-dioxide-based inhibitors. Compounds 5 and 6 are reasonable inhibitors with IC50 values of 25 and 5.5 mu M, respectively. Comparisons of the IC50 values of the three pairs show that the electron-withdrawing sulfone functional group is a beneficial element for the design of plasmin inhibitors. The presence of the sulfone increases inhibitor potency by a factor of 3-5 when compared to inhibitors that are based upon a simple cyclohexanone core.

  DOI：

  10.1021/jo0508954