(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-hydroxypropanoyl]amino]-N-[(2S)-4-amino-1-[[(2S)-3-(4-hydroxyphenyl)-1-[(2S)-2-[[(2S,3S)-3-methyl-1-[[(2S)-3-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]pentanediamide | 1262241-24-6

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: (2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-hydroxypropanoyl]amino]-N-[(2S)-4-amino-1-[[(2S)-3-(4-hydroxyphenyl)-1-[(2S)-2-[[(2S,3S)-3-methyl-1-[[(2S)-3-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]pentanediamide
• CAS: 1262241-24-6
• 化学式: C₆₅H₉₅N₁₃O₁₆S
• 分子量: 1346.61
• InChiKey: FPUPZTSBQILVQV-NWULMWGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  95
• 可旋转键数：
  38
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  476
• 氢给体数：
  14
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  biotin-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Phe-OH 、 (S)-2-氨基-4-甲基-1-((R)-2-甲基环氧乙烷-2-基)-1-戊酮三氟乙酸盐 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以28%的产率得到(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-hydroxypropanoyl]amino]-N-[(2S)-4-amino-1-[[(2S)-3-(4-hydroxyphenyl)-1-[(2S)-2-[[(2S,3S)-3-methyl-1-[[(2S)-3-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]pentanediamide
  参考文献：
  名称：

  HIV Protease-Mediated Activation of Sterically Capped Proteasome Inhibitors and Substrates

  摘要：

  Strategies for selectively killing HIV-infected cells present an appealing alternative to traditional antiretroviral drugs. We show here the first example of an inactive "Trojan horse" molecule that releases a cytotoxic, small-molecule proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept strategy, the protein avidin was used to block entry of the compound into the proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is also feasible without requiring an exogenous protein; a polylysine dendrimer-containing molecule is unable to enter the proteasome until cleaved by HIV-1 protease. These results demonstrate that conditional proteasome inhibitors could prove useful in the development of new tools for chemical biology and future therapeutics.

  DOI：

  10.1021/ja109377p