(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (S)-N-(tert-butoxycarbonyl)-3-hydroxy-α-methyltyrosinate | 86005-08-5

• 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: (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (S)-N-(tert-butoxycarbonyl)-3-hydroxy-α-methyltyrosinate
• 英文别名: 4-Methyl-1,3-dioxol-2-one-5-ylmethyl(S)N-(t-Butoxycarbonyl)-3-hydroxy-alpha-methyltyrosinate；(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (2S)-3-(3,4-dihydroxyphenyl)-2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 86005-08-5
• 化学式: C₂₀H₂₅NO₉
• 分子量: 423.42
• InChiKey: DLHLRIIRLHCKOF-FQEVSTJZSA-N

物化性质

• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (S)-N-(tert-butoxycarbonyl)-3-hydroxy-α-methyltyrosinate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.5h， 生成 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (S)-3-hydroxy-α-methyltyrosinate
  参考文献：
  名称：

  3-Hydroxy-.alpha.-methyltyrosine progenitors, synthesis and evaluation of some (2-oxo-1,3-dioxol-4-yl)methyl esters

  摘要：

  The (5-methyl-2-oxo-1,3- dioxol -4-yl)methyl and (5-tert-butyl-2-oxo-1, 3- dioxol -4-yl)methyl esters of 3-hydroxy-alpha-methyltyrosine (methyldopa) were prepared and evaluated as progenitors of the amino acid. 1H NMR experiments reveal that the esters are converted cleanly to methyldopa and the corresponding alpha-diketone at pH 7.4, with the 5-methyl derivative undergoing hydrolysis faster than the 5-tert-butyl analogue. Bioavailability studies in dogs show that the esters, particularly the 5-methyl derivative, yield significant plasma levels of methyldopa. Both esters are orally effective antihypertensive agents in spontaneously hypertensive (SH) rats. These studies indicate that (2-oxo-1,3- dioxol -4-yl)methyl esters are viable prodrugs for the latentiation of methyldopa.

  DOI：

  10.1021/jm00372a002
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (S)-N-(tert-butoxycarbonyl)-3-hydroxy-α-methyltyrosinate
  参考文献：
  名称：

  3-Hydroxy-.alpha.-methyltyrosine progenitors, synthesis and evaluation of some (2-oxo-1,3-dioxol-4-yl)methyl esters

  摘要：

  The (5-methyl-2-oxo-1,3- dioxol -4-yl)methyl and (5-tert-butyl-2-oxo-1, 3- dioxol -4-yl)methyl esters of 3-hydroxy-alpha-methyltyrosine (methyldopa) were prepared and evaluated as progenitors of the amino acid. 1H NMR experiments reveal that the esters are converted cleanly to methyldopa and the corresponding alpha-diketone at pH 7.4, with the 5-methyl derivative undergoing hydrolysis faster than the 5-tert-butyl analogue. Bioavailability studies in dogs show that the esters, particularly the 5-methyl derivative, yield significant plasma levels of methyldopa. Both esters are orally effective antihypertensive agents in spontaneously hypertensive (SH) rats. These studies indicate that (2-oxo-1,3- dioxol -4-yl)methyl esters are viable prodrugs for the latentiation of methyldopa.

  DOI：

  10.1021/jm00372a002

文献信息

• Oral absorption enhancement of carboxylic acid pharmaceuticals using
  申请人：Merck & Co., Inc.

  公开号：US04654331A1

  公开（公告）日：1987-03-31

  The (5-R-2-oxo-1,3-dioxolen-4-yl)methyl moiety: ##STR1## wherein R is loweralkyl of 1-6 carbon atoms, especially methyl or t-butyl; when utilized as an ester on a pharmaceutical having a carboxylic acid functionality, enhances oral absorption of the pharmaceutical. This effect is applicable to a broad range of pharmaceutically active substances, including antibiotics, and antihypertensives as well as other classes of therapeutic agents.

  （5-R-2-氧代-1,3-二氧杂环戊-4-基）甲基基团：##STR1##其中R是1-6个碳原子的低碳基，特别是甲基或叔丁基；当用于药物的酸性官能团上的酯时，增强了药物的口服吸收。这种效应适用于广泛的药物活性物质，包括抗生素、降压药以及其他类别的治疗剂。