(S)-2-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-4-cyano-butyric acid methyl ester | 211756-70-6

• 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: (S)-2-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-4-cyano-butyric acid methyl ester
• 英文别名: Cbz-Leu-Phe-Abu(CN)-OMe；methyl (2S)-4-cyano-2-[[(2S)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropanoyl]amino]butanoate
• CAS: 211756-70-6
• 化学式: C₂₉H₃₆N₄O₆
• 分子量: 536.628
• InChiKey: ULFBILYPAOUYKS-SDHOMARFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-4-cyano-butyric acid methyl ester 在 sodium tetrahydroborate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以89%的产率得到{(S)-1-[(S)-1-((S)-3-Cyano-1-hydroxymethyl-propylcarbamoyl)-2-phenyl-ethylcarbamoyl]-3-methyl-butyl}-carbamic acid benzyl ester
  参考文献：
  名称：

  Tripeptide Aldehyde Inhibitors of Human Rhinovirus 3C Protease:  Design, Synthesis, Biological Evaluation, and Cocrystal Structure Solution of P₁ Glutamine Isosteric Replacements

  摘要：

  The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin-like serine proteases were constructed to approximate the binding of peptide substrates, generate transition state models of P-1-P-1' amide cleavage, and propose novel tripeptide aldehydes. Glutaminal derivatives have limitations since they exist predominantly in the cyclic hemiaminal form. Therefore, several isosteric replacements for the P-1 carboxamide side chain were designed and incorporated into the tripeptide aldehydes. These compounds were found to be potent inhibitors of purified HRV-14 3CP with K(i)s ranging from 0.005 to 0.64 mu M. Several have low micromolar antiviral activity when tested against HRV-14-infected H1-HeLa cells. The N-acetyl derivative 3 was also shown to be active against HRV serotypes 2, 16, and 89. High-resolution cocrystal structures of HRV-8 3CP, covalently bound to compounds 3, 15, and 16, were solved. These cocrystal structures were analyzed and compared with our original HRV-14 3CP-substrate and inhibitor models.

  DOI：

  10.1021/jm980071x
• 作为产物：
  描述：

  Boc-L-谷氨酰胺 在 吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.42h， 生成 (S)-2-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-4-cyano-butyric acid methyl ester
  参考文献：
  名称：

  Tripeptide Aldehyde Inhibitors of Human Rhinovirus 3C Protease:  Design, Synthesis, Biological Evaluation, and Cocrystal Structure Solution of P₁ Glutamine Isosteric Replacements

  摘要：

  The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin-like serine proteases were constructed to approximate the binding of peptide substrates, generate transition state models of P-1-P-1' amide cleavage, and propose novel tripeptide aldehydes. Glutaminal derivatives have limitations since they exist predominantly in the cyclic hemiaminal form. Therefore, several isosteric replacements for the P-1 carboxamide side chain were designed and incorporated into the tripeptide aldehydes. These compounds were found to be potent inhibitors of purified HRV-14 3CP with K(i)s ranging from 0.005 to 0.64 mu M. Several have low micromolar antiviral activity when tested against HRV-14-infected H1-HeLa cells. The N-acetyl derivative 3 was also shown to be active against HRV serotypes 2, 16, and 89. High-resolution cocrystal structures of HRV-8 3CP, covalently bound to compounds 3, 15, and 16, were solved. These cocrystal structures were analyzed and compared with our original HRV-14 3CP-substrate and inhibitor models.

  DOI：

  10.1021/jm980071x