[(S)-2-(3,3-Dimethyl-ureido)-1-hydroxymethyl-ethyl]-carbamic acid benzyl ester | 211756-64-8

• 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: [(S)-2-(3,3-Dimethyl-ureido)-1-hydroxymethyl-ethyl]-carbamic acid benzyl ester
• 英文别名: benzyl N-[(2S)-1-(dimethylcarbamoylamino)-3-hydroxypropan-2-yl]carbamate
• CAS: 211756-64-8
• 化学式: C₁₄H₂₁N₃O₄
• 分子量: 295.338
• InChiKey: GCDGZZHUXOODCN-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  90.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(S)-2-(3,3-Dimethyl-ureido)-1-hydroxymethyl-ethyl]-carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到3-((S)-2-Amino-3-hydroxy-propyl)-1,1-dimethyl-urea
  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：

  3-氨基-N-(苄氧基羰基)-L-丙氨酸甲酯 在 sodium tetrahydroborate 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 [(S)-2-(3,3-Dimethyl-ureido)-1-hydroxymethyl-ethyl]-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

文献信息

• Tripeptide Aldehyde Inhibitors of Human Rhinovirus 3C Protease:  Design, Synthesis, Biological Evaluation, and Cocrystal Structure Solution of P₁ Glutamine Isosteric Replacements
  作者：Stephen E. Webber、Koji Okano、Thomas L. Little、Siegfried H. Reich、Yue Xin、Shella A. Fuhrman、David A. Matthews、Robert A. Love、Thomas F. Hendrickson、Amy K. Patick、James W. Meador、Rose Ann Ferre、Edward L. Brown、Clifford E. Ford、Susan L. Binford、Stephen T. Worland

  DOI：10.1021/jm980071x

  日期：1998.7.1

  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.