benzyl (S)-6-(ethanethioamido)-1-oxo-1-(2-oxo-2-phenylethylamino)hexan-2-ylcarbamate | 1125879-56-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl (S)-6-(ethanethioamido)-1-oxo-1-(2-oxo-2-phenylethylamino)hexan-2-ylcarbamate
• 英文别名: (S)-benzyl 6-(ethanethioamido)-1-oxo-1-(2-oxo-2-phenylethylamino)hexan-2-ylcarbamate；benzyl N-[(2S)-6-(ethanethioylamino)-1-oxo-1-(phenacylamino)hexan-2-yl]carbamate
• CAS: 1125879-56-2
• 化学式: C₂₄H₂₉N₃O₄S
• 分子量: 455.578
• InChiKey: FEIVQJFUPOCZQU-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (S)-6-(ethanethioamido)-1-oxo-1-(2-oxo-2-phenylethylamino)hexan-2-ylcarbamate 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 16.0h， 以16.3%的产率得到(S)-benzyl 5-(ethanethioamido)-1-(5-phenyl-1H-imidazol-2-yl)pentylcarbamate
  参考文献：
  名称：

  [EN] SIRTUIN INHIBITORS
  [FR] INHIBITEURS DE SIRTUINE

  摘要：

  这项发明涉及化合物和用于抑制sirtuin酶活性的方法。更具体地，该发明提供了式(I)的化合物，Y__L__Z__D，以及其N-氧化物、水合物、溶剂合物、药用可接受盐、前药和复合物，以及它们的外消旋和内消旋混合物、非对映体和对映体，其中Y、L、Z和D如规范中所定义。

  公开号：

  WO2009026701A1
• 作为产物：
  描述：

  N-alpha-Cbz-L-赖氨酸 在 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 吡啶 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl (S)-6-(ethanethioamido)-1-oxo-1-(2-oxo-2-phenylethylamino)hexan-2-ylcarbamate
  参考文献：
  名称：

  Structure-Based Design of Pseudopeptidic Inhibitors for SIRT1 and SIRT2

  摘要：

  The lack of substrate-bound crystal structures of SIRT1 and SIRT2 complicates the drug design for these targets. In this work, we aim to study whether SIRT3 could serve as a target structure in the design of substrate based pseudopeptidic inhibitors of SIRT1 and SIRT2. We created a binding hypothesis for pseudopeptidic inhibitors, synthesized a series of inhibitors, and studied how well the fulfillment of the binding criteria proposed by the hypothesis correlated with the in vitro inhibitory activities. The chosen approach was further validated by studying docking results between 12 different SIRT3, Sir2Tm, SIRT1 and SIRT2 X-ray structures and homology models in different conformational forms. It was concluded that the created binding hypothesis can be used in the design of the substrate based inhibitors of SIRT1 and SIRT2 although there are some reservations, and it is better to use the substrate-bound structure of SIRT3 instead of the available apo-SIRT2 as the target structure.

  DOI：

  10.1021/jm200590k

文献信息

• Structure-Based Design of Pseudopeptidic Inhibitors for SIRT1 and SIRT2
  作者：Tero Huhtiniemi、Heikki S. Salo、Tiina Suuronen、Antti Poso、Antero Salminen、Jukka Leppänen、Elina Jarho、Maija Lahtela-Kakkonen

  DOI：10.1021/jm200590k

  日期：2011.10.13

  The lack of substrate-bound crystal structures of SIRT1 and SIRT2 complicates the drug design for these targets. In this work, we aim to study whether SIRT3 could serve as a target structure in the design of substrate based pseudopeptidic inhibitors of SIRT1 and SIRT2. We created a binding hypothesis for pseudopeptidic inhibitors, synthesized a series of inhibitors, and studied how well the fulfillment of the binding criteria proposed by the hypothesis correlated with the in vitro inhibitory activities. The chosen approach was further validated by studying docking results between 12 different SIRT3, Sir2Tm, SIRT1 and SIRT2 X-ray structures and homology models in different conformational forms. It was concluded that the created binding hypothesis can be used in the design of the substrate based inhibitors of SIRT1 and SIRT2 although there are some reservations, and it is better to use the substrate-bound structure of SIRT3 instead of the available apo-SIRT2 as the target structure.
• [EN] SIRTUIN INHIBITORS<br/>[FR] INHIBITEURS DE SIRTUINE
  申请人：METHYLGENE INC

  公开号：WO2009026701A1

  公开（公告）日：2009-03-05

  This invention relates to compounds and methods for the inhibition of sirtuin enzymatic activity. More particularly, the invention provides for compounds of formula (I), Y__L__Z__D, and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein Y, L, Z and D are as defined in the specification.

  这项发明涉及化合物和用于抑制sirtuin酶活性的方法。更具体地，该发明提供了式(I)的化合物，Y__L__Z__D，以及其N-氧化物、水合物、溶剂合物、药用可接受盐、前药和复合物，以及它们的外消旋和内消旋混合物、非对映体和对映体，其中Y、L、Z和D如规范中所定义。