cyclo[Aib-Phe-D-Pro-Nle(MeSH)(MeSH)] | 1380239-15-5

• 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[Aib-Phe-D-Pro-Nle(MeSH)(MeSH)]
• 英文别名: (3S,9S,12R)-3-benzyl-6,6-dimethyl-9-(5-sulfanylpentyl)-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone
• CAS: 1380239-15-5
• 化学式: C₂₅H₃₆N₄O₄S
• 分子量: 488.651
• InChiKey: SERPMTYHPFOEHJ-SLFFLAALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-2-tert-butoxycarbonylamino-hex-5-enoic acid methyl ester 在 N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide 、 偶氮二异丁腈 、 氨 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 188.0h， 生成 cyclo[Aib-Phe-D-Pro-Nle(MeSH)(MeSH)]
  参考文献：
  名称：

  Flexible Synthesis and Evaluation of Diverse Anti-Apicomplexa Cyclic Peptides

  摘要：

  A modular approach to synthesize anti-Apicomplexa parasite inhibitors was developed that takes advantage of a pluripotent cyclic tetrapeptide scaffold capable of adjusting appendage and skeletal diversities in only a few steps (one to three steps). The diversification processes make use of selective radical coupling reactions and involve a new example of a reductive carbon nitrogen cleavage reaction with SmI2. The resulting bioactive cyclic peptides have revealed new insights into structural factors that govern selectivity between Apicomplexa parasites such as Toxoplasma and Plasmodium and human cells.

  DOI：

  10.1021/jo4001492

文献信息

• Synthesis, evaluation and molecular modeling of cyclic tetrapeptide histone deacetylase inhibitors as anticancer agents
  作者：Dawei Huang、Xiaohui Li、Lei Sun、Zhilong Xiu、Norikazu Nishino

  DOI：10.1002/psc.2392

  日期：2012.4

  Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(−l‐Am7(S2Py)‐Aib‐l‐Phe(n‐Me)‐d‐Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three

  组蛋白脱乙酰基酶抑制剂（HDACIs）是一类有前途的抗癌药。为了检查识别域的轻微变化是否会改变其抑制活性，我们合成了一系列环（− l‐ Am7（S2Py）‐Aib‐ l‐ Phe（n‐ Me）‐d‐ Pro）衍生物并对其进行了评估HDAC的抑制和抗癌活性。该肽表现出有效的HDAC抑制活性，并用IC 50抑制了三种人类癌细胞系在微摩尔范围内。进行了对接和分子动力学模拟，以探索I类和II类HDAC与这些抑制剂的相互作用机理。结果表明，活性部位的锌离子配位了HDACs的五个原子和抑制剂的硫原子。这些化合物的金属结合域与HDAC2相互作用，并且这些化合物的表面识别域通过氢键与HDAC4相互作用。疏水相互作用也为稳定复合物提供了有利的贡献。从这项研究中获得的结果将有助于我们设计一些可能有效的HDACI的新型环状四肽。版权所有©2012欧洲肽协会和John Wiley＆Sons，Ltd.
• Flexible Synthesis and Evaluation of Diverse Anti-Apicomplexa Cyclic Peptides
  作者：Mariam Traoré、Flore Mietton、Danièle Maubon、Marine Peuchmaur、Flaviane Francisco Hilário、Rossimiriam Pereira de Freitas、Alexandre Bougdour、Aurélie Curt、Marjorie Maynadier、Henri Vial、Hervé Pelloux、Mohamed-Ali Hakimi、Yung-Sing Wong

  DOI：10.1021/jo4001492

  日期：2013.4.19

  A modular approach to synthesize anti-Apicomplexa parasite inhibitors was developed that takes advantage of a pluripotent cyclic tetrapeptide scaffold capable of adjusting appendage and skeletal diversities in only a few steps (one to three steps). The diversification processes make use of selective radical coupling reactions and involve a new example of a reductive carbon nitrogen cleavage reaction with SmI2. The resulting bioactive cyclic peptides have revealed new insights into structural factors that govern selectivity between Apicomplexa parasites such as Toxoplasma and Plasmodium and human cells.