(benzyloxycarbonyl)methyl di-tert-butyl phosphate | 130985-36-3

• 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: (benzyloxycarbonyl)methyl di-tert-butyl phosphate
• 英文别名: benzyl [(di-tert-butoxyphosphoryl)oxy]acetate；(di-tert-butoxy-phosphoryloxy)-acetic acid benzyl ester；benzyl 2-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]acetate
• CAS: 130985-36-3
• 化学式: C₁₇H₂₇O₆P
• 分子量: 358.372
• InChiKey: MWNCBTPGJKBNSH-UHFFFAOYSA-N

物化性质

• 沸点：
  418.9±28.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (benzyloxycarbonyl)methyl di-tert-butyl phosphate 在 palladium on activated charcoal 氢气 、 N,N'-二异丙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 N-α-acetyl>l-prolyl>-L-phenylalanyl>-N^α-methyl-L-histydyl>-5(S)-amino-4(S)-hydroxy-2(S)-isopropyl-7-methyloctanoyl>-L-isoleucyl>-2-pyridylmethylamine
  参考文献：
  名称：

  Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in a human renin-infused rat model and in conscious sodium-depleted monkeys

  摘要：

  We previously reported that Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]?? -Ile-Amp (1) is a potent and specific inhibitor of human renin in vitro. It was shown to resist degradation by selected proteases and a rat liver homogenate. It was shown to inhibit plasma renin activity and to reduce blood pressure in renin-dependent-animal models both by the intravenous and by the oral routes using dilute citric acid as vehicle. In an effort to discover compounds with improved pharmacological efficacy, we set out to modify the physical characteristics of this highly lipophilic renin inhibitor by incorporation of hydrophilic end groups. We report here a variety of water-solubilizing groups and the resulting structure-activity relationship of these compounds. They all maintain an extremely high level of enzyme inhibitory activity in vitro. Evaluation of these potent renin inhibitors in a human renin infused rat model suggests that some of these compounds exhibit improved pharmacological efficacy in vivo. This observation was further confirmed in the conscious sodium-depleted cynomolgus monkey. Importantly, the oral efficacy was demonstrated in a water vehicle in the absence of citric acid.

  DOI：

  10.1021/jm00106a026
• 作为产物：
  描述：

  N,N-二乙基亚磷酰胺二叔丁酯 在 四氮唑 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (benzyloxycarbonyl)methyl di-tert-butyl phosphate
  参考文献：
  名称：

  Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in a human renin-infused rat model and in conscious sodium-depleted monkeys

  摘要：

  We previously reported that Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]?? -Ile-Amp (1) is a potent and specific inhibitor of human renin in vitro. It was shown to resist degradation by selected proteases and a rat liver homogenate. It was shown to inhibit plasma renin activity and to reduce blood pressure in renin-dependent-animal models both by the intravenous and by the oral routes using dilute citric acid as vehicle. In an effort to discover compounds with improved pharmacological efficacy, we set out to modify the physical characteristics of this highly lipophilic renin inhibitor by incorporation of hydrophilic end groups. We report here a variety of water-solubilizing groups and the resulting structure-activity relationship of these compounds. They all maintain an extremely high level of enzyme inhibitory activity in vitro. Evaluation of these potent renin inhibitors in a human renin infused rat model suggests that some of these compounds exhibit improved pharmacological efficacy in vivo. This observation was further confirmed in the conscious sodium-depleted cynomolgus monkey. Importantly, the oral efficacy was demonstrated in a water vehicle in the absence of citric acid.

  DOI：

  10.1021/jm00106a026

文献信息

• ANTIMICROBIAL OXAZOLIDINONE PRODRUGS
  申请人：Macielag Mark J.

  公开号：US20080027053A1

  公开（公告）日：2008-01-31

  This invention includes oxazolidinone prodrug compounds of Formula (I) and Formula (II) as defined herein. The prodrugs are convertible by natural biological processes into an active ingredient possessed of antimicrobial properties useful in treating bacterial infections in mammals.

  这项发明包括本文所定义的Formula (I)和Formula (II)的噁唑烷酮前药化合物。这些前药可以通过自然生物过程转化为一种具有抗微生物特性的活性成分，可用于治疗哺乳动物体内的细菌感染。
• [EN] PRODRUG MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] MODULATEURS DE PROMÉDICAMENTS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2020077217A1

  公开（公告）日：2020-04-16

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾病和症状的化合物、组合物和方法。
• Antimicrobial oxazolidinone prodrugs
  申请人：Janssen Pharmaceutica N.V.

  公开号：US07776855B2

  公开（公告）日：2010-08-17

  This invention includes oxazolidinone prodrug compounds of Formula (I) and Formula (II) as defined herein. The prodrugs are convertible by natural biological processes into an active ingredient possessed of antimicrobial properties useful in treating bacterial infections in mammals.

  本发明涉及Formula(I)和Formula(II)的噁唑烷酮前药化合物，如本文所定义。这些前药化合物可以通过自然的生物过程转化为具有抗微生物活性的活性成分，用于治疗哺乳动物的细菌感染。
• Nanoscale Ionic Diodes with Tunable and Switchable Rectifying Behavior
  作者：Michael X. Macrae、Steven Blake、Michael Mayer、Jerry Yang

  DOI：10.1021/ja909876h

  日期：2010.2.17

  Nanoscale ionic diodes have attracted interest as circuit elements for development of nanofluidic devices for a variety of applications. including biosensing, constructing artificial cells, and engineering biological batteries. This paper presents a bottom-up. Self-assembly approach for constructing nanopores with rectified conductance behavior in a membrane using semisynthetic derivatives of the ion-channel-forming peptide gramicidin A. The capability to individually access each half of a dimeric gramicidin channel makes it possible to generate asymmetric channels ill a membrane that exhibit diodelike conductance properties. The modular nature of these self-assembled channels affords the possibility of tuning their rectifying conductance properties by simple replacement of one peptide derivative with another in the membrane. Additionally, introduction of an external stimulus there, an enzyme) to change the Functional group attached to one side of the gramicidin pore induces diodelike conductance behavior in previously nonrectified channels, demonstrating the possibility of switching the conductance properties of these nanopores in situ in a controlled manner.
• TRAISRIVONGS, SUVIT;PALS, DONALD T.;DUCHARME, DONALD W.;TURNER, STEVE R.;+, J. MED. CHEM., 34,(1991) N, C. 633-642
  作者：TRAISRIVONGS, SUVIT、PALS, DONALD T.、DUCHARME, DONALD W.、TURNER, STEVE R.、+

  DOI：——

  日期：——