tert-butyl (S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate | 1387564-76-2

• 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: tert-butyl (S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate
• 英文别名: tert-butyl N-[(2S)-1-[(2S)-2-[[(1R)-1-bis(4-methylsulfanylphenoxy)phosphoryl-2-methylpropyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1387564-76-2
• 化学式: C₃₃H₄₈N₃O₇PS₂
• 分子量: 693.866
• InChiKey: MYIQHDSRNXKCMI-TWLDFKIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  174
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 14.0h， 生成 tert-butyl 2-(4-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethoxy)phenoxy)acetate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x
• 作为产物：
  描述：

  4-(甲硫基)苯酚 在 氢溴酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成 tert-butyl (S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x

文献信息

• A BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase
  作者：Anna-Christina Schulz-Fincke、Michael Blaut、Annett Braune、Michael Gütschow

  DOI：10.1021/acsmedchemlett.7b00533

  日期：2018.4.12

  of biomedical studies. The chemotype of peptidic phosphonates was employed for the design of a new activity-based probe for human leukocyte elastase. Its structure combines the phosphonate warhead with an adequate peptide portion and a BODIPY fluorophore with a clickable ethinylphenyl moiety at meso position. The probe 6 was assembled by copper-catalyzed alkyne–azide 1,3-dipolar cycloaddition. It was

  人白细胞弹性蛋白酶在多种炎性疾病中起关键作用，并且是生物医学研究的重要课题。肽膦酸酯的化学型用于设计新的基于活性的人白细胞弹性蛋白酶探针。其结构结合了膦酸酯弹头具有足够的肽部分和BODIPY荧光团与一个可点击的ethinylphenyl部分内消旋位置。探针6由铜催化的炔-叠氮化物1,3-偶极环加成组装而成。它被表征为一种活性的定点弹性蛋白酶抑制剂，具有88400 M –1 s –1的二级失活速率常数。适合度6通过凝胶内荧光分析证实了其作为人白细胞弹性蛋白酶的荧光探针。针对一组相关蛋白酶的标记实验和抑制数据强调了探针对靶向白细胞弹性蛋白酶的选择性。