4-[4-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-benzylcarbamoyloxymethoxycarbonylmethoxy]-piperidine-1-carboxylic acid benzyl ester | 502158-13-6

• 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: 4-[4-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-benzylcarbamoyloxymethoxycarbonylmethoxy]-piperidine-1-carboxylic acid benzyl ester
• CAS: 502158-13-6
• 化学式: C₃₅H₃₉N₃O₁₀
• 分子量: 661.709
• InChiKey: KUSPKSXYASJOCC-VWLOTQADSA-N

物化性质

• 沸点：
  844.6±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  48.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  158.8
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-[4-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-benzylcarbamoyloxymethoxycarbonylmethoxy]-piperidine-1-carboxylic acid benzyl ester 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 (3S)-3-methyl-13,15,18-trioxa-1,4,11-triazatricyclo[17.2.2.26,9]pentacosa-6,8,24-triene-2,5,12,16-tetrone
  参考文献：
  名称：

  Synthesis of a novel cyclic prodrug of RGD peptidomimetic to improve its cell membrane permeation

  摘要：

  The objective of this work was to synthesize cyclic prodrug 2 derived from the parent RGD peptidomimetic 1 and to evaluate its chemical and enzymatic stabilities and antithrombic activity. Cyclic prodrug 2 was formed to improve the cell membrane permeation of RGD peptidomimetic 1 by transiently masking the unfavorable physicochemical properties of compound 1. Cyclic prodrug 2 was synthesized by linking the amino and carboxylic acid groups of parent 1 via the (acyloxy)alkoxy promoiety. The prodrug-to-drug conversion of cyclic prodrug 2 was evaluated in isolated esterase and human plasma in the absence and presence of the esterase inhibitor paraoxon. The rate of hydrolysis of cyclic prodrug 2 was significantly faster in plasma (t(1/2) = 33.5 +/- 0.6 min) than in PBS (t(1/2) = 314 +/- 11 min). Cyclic prodrug 2 was converted by esterase to the parent compound 1 and this conversion was inhibited by an esterase inhibitor, paraoxon. The IC50 (4 muM) of cyclic prodrug 2 was higher than the IC50 (1.9 muM) of parent drug 1. The antithrombic activity of cyclic prodrug 2 depends on the incubation time in platelet-rich plasma; the activity increases with incubation time, suggesting that the prodrug-to-drug conversion is time-dependent and mediated by esterase. Cyclic prodrug 2 was more stable under acidic and neutral conditions than under basic conditions, suggesting that handling and formulation of this prodrug should be undertaken under acidic conditions. (C) 2002 Elsevier Science (USA). All rights reserved.

  DOI：

  10.1016/s0045-2068(02)00013-5
• 作为产物：
  描述：

  4-[(叔丁氧羰基氨基)甲基]苯甲酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 4-[4-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-benzylcarbamoyloxymethoxycarbonylmethoxy]-piperidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Synthesis of a novel cyclic prodrug of RGD peptidomimetic to improve its cell membrane permeation

  摘要：

  The objective of this work was to synthesize cyclic prodrug 2 derived from the parent RGD peptidomimetic 1 and to evaluate its chemical and enzymatic stabilities and antithrombic activity. Cyclic prodrug 2 was formed to improve the cell membrane permeation of RGD peptidomimetic 1 by transiently masking the unfavorable physicochemical properties of compound 1. Cyclic prodrug 2 was synthesized by linking the amino and carboxylic acid groups of parent 1 via the (acyloxy)alkoxy promoiety. The prodrug-to-drug conversion of cyclic prodrug 2 was evaluated in isolated esterase and human plasma in the absence and presence of the esterase inhibitor paraoxon. The rate of hydrolysis of cyclic prodrug 2 was significantly faster in plasma (t(1/2) = 33.5 +/- 0.6 min) than in PBS (t(1/2) = 314 +/- 11 min). Cyclic prodrug 2 was converted by esterase to the parent compound 1 and this conversion was inhibited by an esterase inhibitor, paraoxon. The IC50 (4 muM) of cyclic prodrug 2 was higher than the IC50 (1.9 muM) of parent drug 1. The antithrombic activity of cyclic prodrug 2 depends on the incubation time in platelet-rich plasma; the activity increases with incubation time, suggesting that the prodrug-to-drug conversion is time-dependent and mediated by esterase. Cyclic prodrug 2 was more stable under acidic and neutral conditions than under basic conditions, suggesting that handling and formulation of this prodrug should be undertaken under acidic conditions. (C) 2002 Elsevier Science (USA). All rights reserved.

  DOI：

  10.1016/s0045-2068(02)00013-5