Cbz-D-Ser-ψ[(E)-CH=CH]-L-Phe-OBu^t | 524712-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Cbz-D-Ser-ψ[(E)-CH=CH]-L-Phe-OBu^t
• 英文别名: tert-butyl (E,2R,5S)-2-benzyl-6-hydroxy-5-(phenylmethoxycarbonylamino)hex-3-enoate
• CAS: 524712-79-6
• 化学式: C₂₅H₃₁NO₅
• 分子量: 425.525
• InChiKey: RRKDYARFVWVBPU-TYOAQRMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cbz-D-Ser-ψ[(E)-CH=CH]-L-Phe-OBu^t 在 吡啶 、 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 氯仿 、 水 为溶剂， 反应 6.5h， 生成 N-[1(S)-(2-naphthylthiomethyl)-4(R)-[2(R,S)-oxiranyl]-5-phenylpent-2(E)-enyl](phenylmethoxy)formamide
  参考文献：
  名称：

  Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit Nanomolar Potency against Multidrug Resistant HIV-1 Strains

  摘要：

  Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K-i = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC50 = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P-1-P-2 position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K-i = 0.38 nM, IC50 = 160 nM).

  DOI：

  10.1021/jm020537i
• 作为产物：
  描述：

  1(R)-[2-(tert-butyldimethylsiloxy)-1(R)-[[N-(phenylmethoxy)carbonyl]amino]ethyl]prop-2-enyl acetate 在 吡啶 、 甲醇 、 六氟合硅酸 、 sodium carbonate 、 臭氧 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 氯仿 、 乙酸乙酯 、 乙腈 为溶剂， 反应 4.75h， 生成 Cbz-D-Ser-ψ[(E)-CH=CH]-L-Phe-OBu^t
  参考文献：
  名称：

  Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit Nanomolar Potency against Multidrug Resistant HIV-1 Strains

  摘要：

  Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K-i = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC50 = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P-1-P-2 position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K-i = 0.38 nM, IC50 = 160 nM).

  DOI：

  10.1021/jm020537i

文献信息

• Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit Nanomolar Potency against Multidrug Resistant HIV-1 Strains
  作者：Hirokazu Tamamura、Yasuhiro Koh、Satoshi Ueda、Yoshikazu Sasaki、Tomonori Yamasaki、Manabu Aoki、Kenji Maeda、Yoriko Watai、Hisashi Arikuni、Akira Otaka、Hiroaki Mitsuya、Nobutaka Fujii

  DOI：10.1021/jm020537i

  日期：2003.4.1

  Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K-i = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC50 = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P-1-P-2 position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K-i = 0.38 nM, IC50 = 160 nM).