(4S)-4-[N-(Ac-Asp(O-tBu)-D-Glu(O-tBu)-Leu-Ile-Cha)-amino]-1-(thiazol-2-yl)-1-hexen-3-one | 622841-19-4

• 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: (4S)-4-[N-(Ac-Asp(O-tBu)-D-Glu(O-tBu)-Leu-Ile-Cha)-amino]-1-(thiazol-2-yl)-1-hexen-3-one
• CAS: 622841-19-4
• 化学式: C₄₉H₇₉N₇O₁₁S
• 分子量: 974.273
• InChiKey: JWLQMYRQKKFJMP-LWYUMQMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.98
• 重原子数：
  68.0
• 可旋转键数：
  26.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  257.16
• 氢给体数：
  6.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (4S)-4-[N-(Ac-Asp(O-tBu)-D-Glu(O-tBu)-Leu-Ile-Cha)-amino]-1-(thiazol-2-yl)-1-hexen-3-one 在 palladium on activated charcoal 三乙基硅烷 、 氢气 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (R)-4-((S)-2-Acetylamino-3-carboxy-propionylamino)-4-((S)-1-{(1S,2S)-1-[(S)-2-cyclohexyl-1-((S)-1-ethyl-2-oxo-4-thiazol-2-yl-butylcarbamoyl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-3-methyl-butylcarbamoyl)-butyric 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：

  (4S)-4-[N-(tert-butoxycarbonyl)amino]-3-hydroxy-1-(thiazol-2-yl)-1-hexene 在 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 38.0h， 生成 (4S)-4-[N-(Ac-Asp(O-tBu)-D-Glu(O-tBu)-Leu-Ile-Cha)-amino]-1-(thiazol-2-yl)-1-hexen-3-one
  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