β-amino-α-(trifluoromethyl)cyclohexanepropanol | 158211-80-4

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 卤代醇
• 英文名称: β-amino-α-(trifluoromethyl)cyclohexanepropanol
• 英文别名: 2-hydroxy-3-amino-1,1,1-trifluoro-4-cyclohexylbutane；3-Amino-4-cyclohexyl-1,1,1-trifluorobutan-2-ol
• CAS: 158211-80-4
• 化学式: C₁₀H₁₈F₃NO
• 分子量: 225.254
• InChiKey: HAWYUDDIJZYSRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  β-amino-α-(trifluoromethyl)cyclohexanepropanol 在 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 N-[1-(cyclohexylmethyl)-3,3,3-trifluoro-2-oxopropyl]-N²-{N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl}-L-leucinamide
  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
• 作为产物：
  描述：

  3-环己基丙酸 在 palladium dihydroxide 盐酸 、 甲醇 、 二苯基膦叠氮化物 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 46.5h， 生成 β-amino-α-(trifluoromethyl)cyclohexanepropanol
  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

文献信息

• Fluorine containing renin inhibitors
  申请人：Pfizer Inc.

  公开号：US04855303A1

  公开（公告）日：1989-08-08

  Polypeptides containing fluorinated cyclostatine derivatives as antihypertensive agents.

  聚肽含有氟代环丙氨酸衍生物，作为降压剂。
• INHIBITORS OF ANGIOTENSIN I CHYMASE(S) INCLUDING HUMAN HEART CHYMASE
  申请人：PFIZER INC.

  公开号：EP0644892A1

  公开（公告）日：1995-03-29
• PHARMACEUTICAL COMPOSITIONS CONTAINING POLYMER AND DRUG ASSEMBLIES
  申请人：Pfizer Products Inc.

  公开号：EP1401399A2

  公开（公告）日：2004-03-31
• PHARMACEUTICAL COMPOSITIONS COMPRISING A SOLID AMORPHOUS DISPERSION OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1469831A1

  公开（公告）日：2004-10-27
• METHOD OF INHIBITING REMNANT LIPOPROTEIN PRODUCTION
  申请人：Japan Tobacco Inc.

  公开号：EP1670446A2

  公开（公告）日：2006-06-21