(S)-2-(3-Cyclohexyl-3-methyl-ureido)-4-methyl-pentanoic acid benzyl ester | 142379-84-8

• 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: (S)-2-(3-Cyclohexyl-3-methyl-ureido)-4-methyl-pentanoic acid benzyl ester
• 英文别名: benzyl (2S)-2-[[cyclohexyl(methyl)carbamoyl]amino]-4-methylpentanoate
• CAS: 142379-84-8
• 化学式: C₂₁H₃₂N₂O₃
• 分子量: 360.497
• InChiKey: CWOYVKYBTCPUQX-IBGZPJMESA-N

物化性质

• 沸点：
  528.8±29.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-(3-Cyclohexyl-3-methyl-ureido)-4-methyl-pentanoic acid benzyl ester 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 为溶剂， 反应 20.0h， 生成 2-[(R)-1-[(S)-2-(3-Cyclohexyl-3-methyl-ureido)-4-methyl-pentanoylamino]-2-(1-methyl-1H-indol-3-yl)-ethyl]-5-methyl-oxazole-4-carboxylic acid benzyl ester
  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：

  N-甲基环己胺 、 L-亮氨酸苄酯对甲苯磺酸盐 、 N,N'-羰基二咪唑 在 三乙胺 作用下， 生成 (S)-2-(3-Cyclohexyl-3-methyl-ureido)-4-methyl-pentanoic acid benzyl ester
  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