N-((cyclohexylamino)carbonyl)leucine benzyl ester | 142380-57-2

• 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: N-((cyclohexylamino)carbonyl)leucine benzyl ester
• 英文别名: benzyl (2S)-2-(cyclohexylcarbamoylamino)-4-methylpentanoate
• CAS: 142380-57-2
• 化学式: C₂₀H₃₀N₂O₃
• 分子量: 346.47
• InChiKey: XNBPXSQJAIDWOO-SFHVURJKSA-N

物化性质

• 沸点：
  523.7±29.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-((cyclohexylamino)carbonyl)leucine benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以90%的产率得到(S)-2-(3-Cyclohexyl-ureido)-4-methyl-pentanoic 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：

  L-亮氨酸苄酯对甲苯磺酸盐 、 环己胺 、 N,N'-羰基二咪唑 在 三乙胺 作用下， 生成 N-((cyclohexylamino)carbonyl)leucine 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

文献信息

• [EN] ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES D'ENDOTHELINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1995008550A1

  公开（公告）日：1995-03-30

  (EN) A compound of formula (I) or a pharmaceutically acceptable salt thereof, as well as processes for and intermediates in the preparation thereof, and methods and compositions of antagonizing endothelin.(FR) Composé représenté par la formule (I), ou un de ses sels pharmaceutiquement acceptable, ainsi que procédés et intermédiaires servant à leur préparation, procédés et compositions antagonistes de l'endothéline.