benzyl (S)-5-((S)-2-acetamidopropanamido)-6-((S)-1-(methylamino)-1-oxopropan-2-ylamino)-6-oxohexylcarbamate | 1334230-93-1

• 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 (S)-5-((S)-2-acetamidopropanamido)-6-((S)-1-(methylamino)-1-oxopropan-2-ylamino)-6-oxohexylcarbamate
• 英文别名: Ac-Ala-Lys(Cbz)-Ala-NHMe；benzyl N-[(5S)-5-[[(2S)-2-acetamidopropanoyl]amino]-6-[[(2S)-1-(methylamino)-1-oxopropan-2-yl]amino]-6-oxohexyl]carbamate
• CAS: 1334230-93-1
• 化学式: C₂₃H₃₅N₅O₆
• 分子量: 477.561
• InChiKey: OPRNFVOXOKRXDW-BXWFABGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl (S)-5-((S)-2-acetamidopropanamido)-6-((S)-1-(methylamino)-1-oxopropan-2-ylamino)-6-oxohexylcarbamate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以100%的产率得到(S)-2-((S)-2-acetamidopropanamido)-6-amino-N-((S)-1-(methylamino)-1-oxopropan-2-yl)hexanamide
  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
• 作为产物：
  描述：

  N'-芴甲氧羰基-N-苄氧羰基-L-赖氨酸 在 哌啶 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.58h， 生成 benzyl (S)-5-((S)-2-acetamidopropanamido)-6-((S)-1-(methylamino)-1-oxopropan-2-ylamino)-6-oxohexylcarbamate
  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