N5-[Bis[[(phenylmethoxy)carbonyl]amino]methylene]-L-ornithine methyl ester | 899442-97-8

• 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: N5-[Bis[[(phenylmethoxy)carbonyl]amino]methylene]-L-ornithine methyl ester
• 英文别名: methyl (2S)-2-amino-5-[bis(phenylmethoxycarbonylamino)methylideneamino]pentanoate
• CAS: 899442-97-8
• 化学式: C₂₃H₂₈N₄O₆
• 分子量: 456.499
• InChiKey: BNDUVIOTPTZSML-IBGZPJMESA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-Boc-L-缬氨酸 、 N5-[Bis[[(phenylmethoxy)carbonyl]amino]methylene]-L-ornithine methyl ester 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 以98%的产率得到
  参考文献：
  名称：

  Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives

  摘要：

  Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.07.042

文献信息

• Histone deacetylase inhibitors: synthesis of cyclic tetrapeptides and their triazole analogs
  作者：Erinprit K. Singh、Lidia A. Nazarova、Stephanie A. Lapera、Leslie D. Alexander、Shelli R. McAlpine

  DOI：10.1016/j.tetlet.2010.06.050

  日期：2010.8

  Synthesis of nine macrocyclic peptide HDAC inhibitors and three triazole derivatives is described. HDAC inhibitory activity of these compounds against HeLa cell lysate is evaluated. The biological data demonstrate that incorporation of a triazole unit improves the HDAC inhibitory activity.

  描述了九个大环肽 HDAC 抑制剂和三个三唑衍生物的合成。评估了这些化合物对 HeLa 细胞裂解物的 HDAC 抑制活性。生物学数据表明，三唑单元的掺入提高了 HDAC 抑制活性。
• Liquid phase parallel synthesis of iminodiacetic acid derivatives
  作者：Soan Cheng、Daniel D. Comer、Peter L. Myers、John Saunders

  DOI：10.1016/s0040-4039(99)01915-2

  日期：1999.12

  Liquid phase parallel synthesis has been developed to synthesize a novel series of iminodiacetic acid derivatives targeting the integrin receptors. This library was synthesized using a four-step reaction sequence. In each step of the sequence, the PEG-bound products were precipitated selectively and the excess reagents and the by-products were removed by simple filtration. The most notable result was

  已经开发了液相平行合成以合成靶向整联蛋白受体的一系列新的亚氨基二乙酸衍生物。使用四步反应序列合成该文库。在该序列的每个步骤中，选择性地沉淀结合PEG的产物，并通过简单过滤除去过量的试剂和副产物。最显着的结果是文库成员的纯度很高（> 95％）。
• Synthesis and biological evaluation of histone deacetylase inhibitors that are based on FR235222: A cyclic tetrapeptide scaffold
  作者：Erinprit K. Singh、Suchitra Ravula、Chung-Mao Pan、Po-Shen Pan、Robert C. Vasko、Stephanie A. Lapera、Sujith V.W. Weerasinghe、Mary Kay H. Pflum、Shelli R. McAlpine

  DOI：10.1016/j.bmcl.2008.03.047

  日期：2008.4

  We outline the synthesis of six novel derivatives that are based on a recently discovered HDAC inhibitor FR235222. Our work is the first report utilizing a novel binding element, guanidine, as metal coordinators in HDAC inhibitors. Further, we demonstrate that these compounds show cytotoxicity that parallels their ability to inhibit deacetylase activity, and that the most potent compounds maintain

  我们概述了基于最近发现的 HDAC 抑制剂 FR235222 的六种新型衍生物的合成。我们的工作是第一份利用新型结合元素胍作为 HDAC 抑制剂中的金属配位剂的报告。此外，我们证明这些化合物显示出与其抑制脱乙酰酶活性的能力平行的细胞毒性，并且最有效的化合物在 1 位保持 L-Phe，在 4 位保持 D-Pro。这些化合物展示了胰腺癌细胞系 BxPC3，表明可以成功利用胍单元来抑制 HDAC 活性。