(S)-2-(2-((S)-2-amino-5-guanidinopentanamido)acetamido)-N1,N8-bis(2-aminophenyl)octanediamide | 1186489-71-3

• 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: (S)-2-(2-((S)-2-amino-5-guanidinopentanamido)acetamido)-N1,N8-bis(2-aminophenyl)octanediamide
• 英文别名: (2S)-2-[[2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N,N'-bis(2-aminophenyl)octanediamide
• CAS: 1186489-71-3
• 化学式: C₂₈H₄₂N₁₀O₄
• 分子量: 582.706
• InChiKey: VEQAODWCBATLTK-REWPJTCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  42
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  259
• 氢给体数：
  9
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  甘氨酸烯丙酯 、 FMOC-L-2-氨基辛二酸 、 Fmoc-甘氨酸 、 邻苯二胺 、 Fmoc-Pbf-L-精氨酸 在 trityl chloride resin 、 N,N-二异丙基乙胺 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以6%的产率得到N-(2-aminophenyl)-6-((2S,8S)-8-(3-guanidinopropyl)-3,6,9,12-tetraoxo-1,4,7,10-tetraazacyclododecan-2-yl)hexanamide
  参考文献：
  名称：

  Design and synthesis of novel hybrid benzamide–peptide histone deacetylase inhibitors

  摘要：

  We designed and synthesized a series of novel hybrid histone deacetylase inhibitors based on conjugation of benzamide-type inhibitors with either linear or cyclic peptides. Linear tetrapeptides (compounds 13 and 14), cyclic tetrapeptides (compounds 1 and 11), and heptanediamide-peptide conjugates (compounds 10, 12, 15 and 16) were synthesized through on-resin solid-phase peptide synthesis (SPPS). All compounds were found to be moderate HDAC1 and HDAC3 inhibitors, with IC50 values ranging from 1.3 mu M to 532 mu M. Interestingly, compound 15 showed 19-fold selectivity for HDAC3 versus HDAC1. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.085

文献信息

• Design and synthesis of novel hybrid benzamide–peptide histone deacetylase inhibitors
  作者：Fang Hu、C. James Chou、Joel M. Gottesfeld

  DOI：10.1016/j.bmcl.2009.03.085

  日期：2009.7

  We designed and synthesized a series of novel hybrid histone deacetylase inhibitors based on conjugation of benzamide-type inhibitors with either linear or cyclic peptides. Linear tetrapeptides (compounds 13 and 14), cyclic tetrapeptides (compounds 1 and 11), and heptanediamide-peptide conjugates (compounds 10, 12, 15 and 16) were synthesized through on-resin solid-phase peptide synthesis (SPPS). All compounds were found to be moderate HDAC1 and HDAC3 inhibitors, with IC50 values ranging from 1.3 mu M to 532 mu M. Interestingly, compound 15 showed 19-fold selectivity for HDAC3 versus HDAC1. (C) 2009 Elsevier Ltd. All rights reserved.