cyclo(-L-Ae9(epo)-Aib-L-Phe-D-Pro-) | 887277-65-8

• 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: cyclo(-L-Ae9(epo)-Aib-L-Phe-D-Pro-)
• 英文别名: (3S,9S,14aR)-9-benzyl-6,6-dimethyl-3-[5-(oxiran-2-yl)pentyl]-tetradecahydropyrrolo[1,2-a][,,,]cyclododecane-1,4,7,10-tetrone；(3S,9S,12R)-3-benzyl-6,6-dimethyl-9-[5-(oxiran-2-yl)pentyl]-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone
• CAS: 887277-65-8
• 化学式: C₂₇H₃₈N₄O₅
• 分子量: 498.623
• InChiKey: QKELJHBCMVDGRQ-GEIYVISESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  cyclo(-L-Ae9(epo)-Aib-L-Phe-D-Pro-) 在 溶剂黄146 、 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以93%的产率得到(5S,11S,13aR)-5-Benzyl-11-(7-bromo-6-hydroxy-heptyl)-8,8-dimethyl-decahydro-3a,6,9,12-tetraaza-cyclopentacyclododecene-4,7,10,13-tetraone
  参考文献：
  名称：

  Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases

  摘要：

  A series of chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamyclocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2005.12.063
• 作为产物：
  描述：

  Z-L-Phe-D-Pro-OtBu 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 cyclo(-L-Ae9(epo)-Aib-L-Phe-D-Pro-)
  参考文献：
  名称：

  Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases

  摘要：

  A series of chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamyclocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2005.12.063

文献信息

• Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition
  作者：Md. Shahidul Islam、Mohammed P. I. Bhuiyan、Md. Nurul Islam、Tienabe Kipassa Nsiama、Naoto Oishi、Tamaki Kato、Norikazu Nishino、Akihiro Ito、Minoru Yoshida

  DOI：10.1007/s00726-011-0947-6

  日期：2012.6

  The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus , consists of alpha-aminoisobutyric acid, -phenylalanine, -proline and an unusual amino acid ()-2-amino-8-(()-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.
• Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases
  作者：Mohammed P.I. Bhuiyan、Tamaki Kato、Tatsuo Okauchi、Norikazu Nishino、Satoko Maeda、Tomonori G. Nishino、Minoru Yoshida

  DOI：10.1016/j.bmc.2005.12.063

  日期：2006.5

  A series of chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamyclocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs. (c) 2006 Published by Elsevier Ltd.