benzyl ((benzyloxy)carbonyl)-L-lysyl-L-alaninate 2,2,2-trifluoroacetate | 956216-27-6

• 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 ((benzyloxy)carbonyl)-L-lysyl-L-alaninate 2,2,2-trifluoroacetate
• CAS: 956216-27-6
• 化学式: C₂HF₃O₂*C₂₄H₃₁N₃O₅
• 分子量: 555.551
• InChiKey: FWXGSFYUSASZJV-ZXRBMNSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  39.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  157.05
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  benzyl ((benzyloxy)carbonyl)-L-lysyl-L-alaninate 2,2,2-trifluoroacetate 、 (3S,4R)-3-hexyl-4-oxooxetane-2-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以47%的产率得到benzyl (2S)-2-[[(2S)-6-[[(2R,3S)-3-hexyl-4-oxooxetane-2-carbonyl]amino]-2-(phenylmethoxycarbonylamino)hexanoyl]amino]propanoate
  参考文献：
  名称：

  A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

  摘要：

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.020
• 作为产物：
  描述：

  L-丙氨酸苄酯对甲苯磺酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 benzyl ((benzyloxy)carbonyl)-L-lysyl-L-alaninate 2,2,2-trifluoroacetate
  参考文献：
  名称：

  A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

  摘要：

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.020

文献信息

• Stable C-Glycoside Sugar and C-Glycoconjugate Mimetics, Method for preparing same and uses Thereof in Particular in Cosmetics and Drugs
  申请人：Castelot-Deliencourt-Godefroy Géraldine

  公开号：US20090318678A1

  公开（公告）日：2009-12-24

  The invention concerns a C-glycoside compound of formula (I); wherein: n is equal to 1 or 2; Y represents H or halogen; X is an alkyl chain bearing at least one amino, amide, acid, ester, carbonyl, alcohol, aryl function or a carbonyl, ester amide, amino, alcohol group; the R's, identical or different, represent a OH or OR′ group where R′ is an alkyl, benzyl, benzoyl, acetyl, pivaloyl, trialkylsilyl, tertiobutyldiphenylsilyl group or one or more sugars; R1 represents OR′, NR″R″′, N3, or a phthalamide with R″ and R″′, identical or different, represent H or an alkyl, aryl, benzyl, benzoyl, acetyl, alkoxycarbonyl, allyloxycarbonyl, benzyloxycarbonyl group; R2 represents H or halogen or a OH, OR, NR″R″′ or N3 group, as well as derivatives thereof in physiologically or pharmaceutically acceptable base, mineral or organic acid-addition salt, hydrate or solvate form. The invention is useful for preparing C-glycoside compounds or C-glycoconjugates applicable in particular in cosmetology, medical imagery, immunology for treating cancer, diabetes, hypertension.

  本发明涉及一种化学式(I)的C-葡萄糖苷化合物；其中：n等于1或2；Y代表H或卤素；X是一个带有至少一个氨基、酰胺、酸、酯、酰基、醇、芳基功能或一个酰基、酯酰胺、氨基、醇基的烷基链；R，相同或不同，代表OH或OR′基团，其中R′是一个烷基、苄基、苯甲酰基、乙酰基、偏戊酰基、三烷基硅基、叔丁基二苯基硅基团或一个或多个糖；R1代表OR′、NR″R″′、N3或具有R″和R″′相同或不同的邻苯二甲酰胺，其中R″和R″′代表H或一个烷基、芳基、苄基、苯甲酰基、乙氧羰基、烯丙氧羰基、苄氧羰基团；R2代表H或卤素或一个OH、OR、NR″R″′或N3基团，以及其在生理学或药学上可接受的碱、矿物酸或有机酸盐、水合物或溶剂化合物形式的衍生物。本发明用于制备C-葡萄糖苷化合物或C-葡糖结合物，特别适用于化妆品学、医学影像学、免疫学以治疗癌症、糖尿病、高血压。