4-(2-acetylamino-3-tert-butoxycarbonyl-propionylamino)-4-[1-(1-{2-cyclohexyl-1-[1-ethyl-4-(4-methoxy-phenyl)-2-oxo-but-3-enylcarbamoyl]-ethylcarbamoyl}-2-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid tert-butyl ester | 622841-18-3

• 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: 4-(2-acetylamino-3-tert-butoxycarbonyl-propionylamino)-4-[1-(1-{2-cyclohexyl-1-[1-ethyl-4-(4-methoxy-phenyl)-2-oxo-but-3-enylcarbamoyl]-ethylcarbamoyl}-2-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid tert-butyl ester
• CAS: 622841-18-3
• 化学式: C₅₃H₈₄N₆O₁₂
• 分子量: 997.283
• InChiKey: DEQLRCIVHFPNKP-SHNHAUHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  71.0
• 可旋转键数：
  27.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  253.5
• 氢给体数：
  6.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  4-(2-acetylamino-3-tert-butoxycarbonyl-propionylamino)-4-[1-(1-{2-cyclohexyl-1-[1-ethyl-4-(4-methoxy-phenyl)-2-oxo-but-3-enylcarbamoyl]-ethylcarbamoyl}-2-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid tert-butyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (4R)-4-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-3-cyclohexyl-1-[[(E,3S)-6-(4-methoxyphenyl)-4-oxohex-5-en-3-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Peptide-based inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase): model compounds towards small molecule inhibitors

  摘要：

  From L-alpha-aminobutyric acid (Abu) a set of electrophilic and non-electrophilic replacements for the PI cysteine of substrate and product inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase) serine protease have been synthesised and coupled to a model pentapeptide furnishing a set of hexapeptide inhibitors. Promising inhibitory activities with K-i values of 0.18muM (11b, P1 electrophilic alpha,beta-unsaturated ketone), 0.46 muM (12e, P1 electrophilic alkyl ketone) and 0.98muM (10e, P1 nonelectrophilic alkenyl alcohol as diastereomeric mixture). The reference hexapeptide product inhibitor had a K-i value of 1.54 muM (14, P1 Abu-OH). The electrophilic inhibitors exhibit increased potency as compared with the corresponding product inhibitor, and notably also the non-electrophilic P1 alkenyl alcohol 10e. This represents the first example of non-electrophilic inhibitors that are not P1 amides or product inhibitors. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00190-1
• 作为产物：
  描述：

  4-(2-acetylamino-3-tert-butoxycarbonyl-propionylamino)-4-[1-(1-{2-cyclohexyl-1-[1-ethyl-2-hydroxy-4-(4-methoxy-phenyl)-but-3-enylcarbamoyl]-ethylcarbamoyl}-2-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid tert-butyl ester 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以53%的产率得到4-(2-acetylamino-3-tert-butoxycarbonyl-propionylamino)-4-[1-(1-{2-cyclohexyl-1-[1-ethyl-4-(4-methoxy-phenyl)-2-oxo-but-3-enylcarbamoyl]-ethylcarbamoyl}-2-methyl-butylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid tert-butyl ester
  参考文献：
  名称：

  Peptide-based inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase): model compounds towards small molecule inhibitors

  摘要：

  From L-alpha-aminobutyric acid (Abu) a set of electrophilic and non-electrophilic replacements for the PI cysteine of substrate and product inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase) serine protease have been synthesised and coupled to a model pentapeptide furnishing a set of hexapeptide inhibitors. Promising inhibitory activities with K-i values of 0.18muM (11b, P1 electrophilic alpha,beta-unsaturated ketone), 0.46 muM (12e, P1 electrophilic alkyl ketone) and 0.98muM (10e, P1 nonelectrophilic alkenyl alcohol as diastereomeric mixture). The reference hexapeptide product inhibitor had a K-i value of 1.54 muM (14, P1 Abu-OH). The electrophilic inhibitors exhibit increased potency as compared with the corresponding product inhibitor, and notably also the non-electrophilic P1 alkenyl alcohol 10e. This represents the first example of non-electrophilic inhibitors that are not P1 amides or product inhibitors. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00190-1