(R)-2-(2-tert-butoxycarbonylaminomethyl-thiazol-4-yl)-4-ethyl-4,5-dihydrothiazole-4-carboxylic acid | 1246263-33-1

• 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: (R)-2-(2-tert-butoxycarbonylaminomethyl-thiazol-4-yl)-4-ethyl-4,5-dihydrothiazole-4-carboxylic acid
• 英文别名: (4R)-4-ethyl-2-[2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-1,3-thiazol-4-yl]-5H-1,3-thiazole-4-carboxylic acid
• CAS: 1246263-33-1
• 化学式: C₁₅H₂₁N₃O₄S₂
• 分子量: 371.481
• InChiKey: OQOFILCWRXGDGU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-3-((S)-2-amino-3-methylbutanoyloxy)-pent-4-enoate 、 (R)-2-(2-tert-butoxycarbonylaminomethyl-thiazol-4-yl)-4-ethyl-4,5-dihydrothiazole-4-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以89%的产率得到(3S,2'S,4''R)-tert-butyl 3-(2-(2-(2-(tert-butoxycarbonyl)aminomethyl-thiazol-4-yl)-4-ethyl-4,5-dihydrothiazole-4-carboxamido)-3-methylbutanoyloxy)pent-4-enoate
  参考文献：
  名称：

  Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues

  摘要：

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.

  DOI：

  10.1021/jm100244y
• 作为产物：
  描述：

  (R)-2-ethylcysteine hydrochloride 、 tert-butyl ((4-cyanothiazol-2-yl)methyl)carbamate 在 水 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以49%的产率得到(R)-2-(2-tert-butoxycarbonylaminomethyl-thiazol-4-yl)-4-ethyl-4,5-dihydrothiazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues

  摘要：

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.

  DOI：

  10.1021/jm100244y

文献信息

• Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues
  作者：José A. Souto、Esther Vaz、Ilaria Lepore、Ann-Christin Pöppler、Gianluigi Franci、Rosana Álvarez、Lucia Altucci、Ángel R. de Lera

  DOI：10.1021/jm100244y

  日期：2010.6.24

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.