α-(2,2,2-trifluoro-1-hydroxyethyl)cyclohexanepropanoic acid | 120586-89-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: α-(2,2,2-trifluoro-1-hydroxyethyl)cyclohexanepropanoic acid
• 英文别名: 2-(cyclohexylmethyl)-4,4,4-trifluoro-3-hydroxybutanoic acid
• CAS: 120586-89-2；120586-90-5
• 化学式: C₁₁H₁₇F₃O₃
• 分子量: 254.249
• InChiKey: KGCXMUHNEXTMEP-UHFFFAOYSA-N

物化性质

• 沸点：
  363.1±42.0 °C(predicted)
• 密度：
  1.253±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  α-(2,2,2-trifluoro-1-hydroxyethyl)cyclohexanepropanoic acid 在 盐酸 、 甲醇 、 二苯基膦叠氮化物 、 potassium carbonate 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 22.5h， 生成 <1-(cyclohexylmethyl)-2-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-3,3,3-trifluoropropyl>carbamic acid, phenylmethyl ester
  参考文献：
  名称：

  Activated ketone based inhibitors of human renin

  摘要：

  Application of the concept of activated ketones to the design of novel and potent transition-state analog inhibitors of the aspartyl protease renin is described. Three different classes of peptidic activated ketones were synthesized: 1,1,1-trifluoromethyl ketones, alpha-keto esters, and alpha-diketones. The corresponding alcohols were also evaluated as renin inhibitors in each series. While the trifluoromethyl alcohol 12 (I50 = 4000 nM) was equipotent to the simple methyl alcohol 7 (I50 = 3200 nM), the structurally similar alpha-hydroxy esters (32 and 30, I50's = 5.3 and 4.7 nM, respectively) and alpha-hydroxy ketones (41 and 42, I50 = 23 and 15 nM, respectively) were 150-300-fold more active. The hydrating capability of the activated ketone functionality was important for intrinsic potency in the case of trifluoromethyl ketones, as illustrated by the significantly better activity of trifluoromethyl ketone 13 (I50 = 250 nM) compared to its alcohol analog 12 (I50 = 4000 nM). It was however unimportant for the alpha-keto ester (20 and 31, I50 = 15 and 4.1 nM, respectively) and alpha-diketone (43 and 44, I50 = 52 and 28 nM, respectively) based inhibitors, since their activity was essentially similar to that of the corresponding alcohols. These results collectively suggest that, whereas the trifluoromethyl ketones derive their renin inhibitory potency primarily from their ability to become hydrated, this is not a critical feature for the activity of alpha-dicarbonyl-based inhibitors. The alpha-keto ester and alpha-diketone based renin inhibitors benefit predominantly from the hydrophobic and/or H-bonding type binding interactions of the neighboring ester or acyl group itself, rather than the ability of this group to deactivate the adjacent ketone group and thereby make it susceptible to hydration.

  DOI：

  10.1021/jm00069a001
• 作为产物：
  描述：

  2,2,2-三氟乙醛 、 3-环己基丙酸 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 以67%的产率得到α-(2,2,2-trifluoro-1-hydroxyethyl)cyclohexanepropanoic acid
  参考文献：
  名称：

  Peptidic trifluoromethyl alcohols and ketones a general synthesis and application as renin inhibitors

  摘要：

  DOI：

  10.1016/s0040-4039(00)80575-4

文献信息

• PATEL, DINESH V.;RIELLY-GAUVIN, KATHERINE;RYONO, DENIS E., TETRAHEDRON LETT., 29,(1988) N 37, C. 4665-4680
  作者：PATEL, DINESH V.、RIELLY-GAUVIN, KATHERINE、RYONO, DENIS E.

  DOI：——

  日期：——