benzyl 2-[(1R)-1-[[(2S)-2-[(2-cyclohexylacetyl)amino]-4-methylpentanoyl]amino]-2-(1-methylindol-3-yl)ethyl]-5-methyl-1,3-oxazole-4-carboxylate | 1027234-40-7

• 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 2-[(1R)-1-[[(2S)-2-[(2-cyclohexylacetyl)amino]-4-methylpentanoyl]amino]-2-(1-methylindol-3-yl)ethyl]-5-methyl-1,3-oxazole-4-carboxylate
• CAS: 1027234-40-7
• 化学式: C₃₇H₄₆N₄O₅
• 分子量: 626.796
• InChiKey: CHEQCDFSXGMGJU-IOWSJCHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 2-[(1R)-1-[[(2S)-2-[(2-cyclohexylacetyl)amino]-4-methylpentanoyl]amino]-2-(1-methylindol-3-yl)ethyl]-5-methyl-1,3-oxazole-4-carboxylate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2-[(R)-1-[(S)-2-(2-Cyclohexyl-acetylamino)-4-methyl-pentanoylamino]-2-(1-methyl-1H-indol-3-yl)-ethyl]-5-methyl-oxazole-4-carboxylic acid
  参考文献：
  名称：

  Azole Endothelin Antagonists. 3. Using Δ log P as a Tool To Improve Absorption

  摘要：

  The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter Delta log P. Comparison of urea 2 with a series of well-absorbed compounds using Delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between Delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

  DOI：

  10.1021/jm9505932
• 作为产物：
  描述：

  环己基乙酸 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 benzyl 2-[(1R)-1-[[(2S)-2-[(2-cyclohexylacetyl)amino]-4-methylpentanoyl]amino]-2-(1-methylindol-3-yl)ethyl]-5-methyl-1,3-oxazole-4-carboxylate
  参考文献：
  名称：

  Azole Endothelin Antagonists. 3. Using Δ log P as a Tool To Improve Absorption

  摘要：

  The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter Delta log P. Comparison of urea 2 with a series of well-absorbed compounds using Delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between Delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

  DOI：

  10.1021/jm9505932