benzyl N-[(2S)-1-[[(1S)-1-[3-(ethoxymethyl)spiro[1,2,4-trioxolane-5,2'-adamantane]-3-yl]-2-phenylethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamate | 1256776-34-7

• 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: benzyl N-[(2S)-1-[[(1S)-1-[3-(ethoxymethyl)spiro[1,2,4-trioxolane-5,2'-adamantane]-3-yl]-2-phenylethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 1256776-34-7
• 化学式: C₃₆H₄₈N₂O₇
• 分子量: 620.786
• InChiKey: WCDAIJYXHSAEOL-YRKBYONPSA-N

物化性质

• 沸点：
  769.0±60.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  苄氧羰基-亮氨酰-苯丙氨酸 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 臭氧 、 magnesium 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 mercury dichloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 正戊烷 为溶剂， 反应 0.75h， 生成 benzyl N-[(2S)-1-[[(1S)-1-[3-(ethoxymethyl)spiro[1,2,4-trioxolane-5,2'-adamantane]-3-yl]-2-phenylethyl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity

  摘要：

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.

  DOI：

  10.1021/jm1009567

文献信息

• Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity
  作者：Peter Gibbons、Edite Verissimo、Nuna C. Araujo、Victoria Barton、Gemma L. Nixon、Richard K. Amewu、James Chadwick、Paul A. Stocks、Giancarlo A. Biagini、Abhishek Srivastava、Philip J. Rosenthal、Jiri Gut、Rita C. Guedes、Rui Moreira、Raman Sharma、Neil Berry、M. Lurdes S. Cristiano、Alison E. Shone、Stephen A. Ward、Paul M. O’Neill

  DOI：10.1021/jm1009567

  日期：2010.11.25

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.