(2S)-N-[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]-1-[2-[[2-[[2-[4-[1-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]triazol-4-yl]phenyl]triazol-4-yl]butanoylamino]acetyl]amino]acetyl]amino]acetyl]pyrrolidine-2-carboxamide | 1202186-27-3

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: (2S)-N-[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]-1-[2-[[2-[[2-[4-[1-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]triazol-4-yl]phenyl]triazol-4-yl]butanoylamino]acetyl]amino]acetyl]amino]acetyl]pyrrolidine-2-carboxamide
• CAS: 1202186-27-3
• 化学式: C₇₁H₁₁₉N₂₇O₁₅
• 分子量: 1590.9
• InChiKey: GIFFMQPCWUZTMZ-YKPVFUCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  113
• 可旋转键数：
  57
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  663
• 氢给体数：
  20
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 、 苯酚 作用下， 反应 2.0h， 以100%的产率得到(2S)-N-[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[2-[(2-amino-2-oxoethyl)amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]-1-[2-[[2-[[2-[4-[1-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]triazol-4-yl]phenyl]triazol-4-yl]butanoylamino]acetyl]amino]acetyl]amino]acetyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide

  摘要：

  We describe herein the synthesis and characterization of a new class of histone deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear localization signal peptide. We found that these conjugates inhibited the histone deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity and a twofold increase in HDAC 8 selectivity when compared to SAHA. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.028

文献信息

• Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide
  作者：Joshua C. Canzoneri、Po C. Chen、Adegboyega K. Oyelere

  DOI：10.1016/j.bmcl.2009.10.028

  日期：2009.12

  We describe herein the synthesis and characterization of a new class of histone deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear localization signal peptide. We found that these conjugates inhibited the histone deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity and a twofold increase in HDAC 8 selectivity when compared to SAHA. (C) 2009 Elsevier Ltd. All rights reserved.