1-isocyano-2-methylpropanephosphonic acid di(4-methylthiophenyl) ester | 1275615-39-8

• 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: 1-isocyano-2-methylpropanephosphonic acid di(4-methylthiophenyl) ester
• CAS: 1275615-39-8
• 化学式: C₁₉H₂₂NO₃PS₂
• 分子量: 407.494
• InChiKey: NHOUCVJOUSCBNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  26.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  39.89
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Cbz-DL-蛋氨酸 、 1-isocyano-2-methylpropanephosphonic acid di(4-methylthiophenyl) ester 、 异戊醛 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以60%的产率得到[1-[[1-bis(4-methylsulfanylphenoxy)phosphoryl-2-methylpropyl]amino]-4-methyl-1-oxopentan-2-yl] 4-methylsulfanyl-2-(phenylmethoxycarbonylamino)butanoate
  参考文献：
  名称：

  Phosphonic pseudopeptides as human neutrophil elastase inhibitors—a combinatorial approach

  摘要：

  Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries-products of Ugi and Passerini multicomponent condensations leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-Val(P)(OC6H4-p-Cl)(2), displayed apparent second-order inhibition value at 40,105 M-1 s(-1) as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.008
• 作为产物：
  描述：

  tris(4-(methylthio)phenyl)phosphite 在 氢溴酸 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-isocyano-2-methylpropanephosphonic acid di(4-methylthiophenyl) ester
  参考文献：
  名称：

  Phosphonic pseudopeptides as human neutrophil elastase inhibitors—a combinatorial approach

  摘要：

  Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries-products of Ugi and Passerini multicomponent condensations leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-Val(P)(OC6H4-p-Cl)(2), displayed apparent second-order inhibition value at 40,105 M-1 s(-1) as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.008