dimethyl-4-(2-(tert-butoxycarbonylamino)ethoxy)-2,6-pyridinedicarboxylate | 1085412-34-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: dimethyl-4-(2-(tert-butoxycarbonylamino)ethoxy)-2,6-pyridinedicarboxylate
• 英文别名: dimethyl-4-(2-tert-butoxycarbonylaminoethoxy)-2,6-pyridinedicarboxylate；dimethyl-4-(2-tert-butoxycarbonylamino-ethoxy)-2,6-pyridinecarboxylate；Dimethyl-4-(2-tert-butoxycarbonylamino-ethoxy)-2,6-pyridinedicarboxylate；dimethyl 4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]pyridine-2,6-dicarboxylate
• CAS: 1085412-34-5
• 化学式: C₁₆H₂₂N₂O₇
• 分子量: 354.36
• InChiKey: IWAMEYISQZOJBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dimethyl-4-(2-(tert-butoxycarbonylamino)ethoxy)-2,6-pyridinedicarboxylate 在 1-氯-N,N,2-三甲基丙烯胺 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 Bcl-2 inhibitor PDF
  参考文献：
  名称：

  Pyridostatin类化合物及其制备方法与应用

  摘要：

  本发明提供一种Pyridostatin化合物及其制备方法与应用。所述Pyridostatin化合物的结构式如式I所示。该化合物及其药学上可接受的盐对人肺癌和人结肠癌表现出好的抗肿瘤活性。

  公开号：

  CN104045629B
• 作为产物：
  描述：

  4-氧代-1,4-二氢-2,6-吡啶二甲酸 在 偶氮二甲酸二异丙酯 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 dimethyl-4-(2-(tert-butoxycarbonylamino)ethoxy)-2,6-pyridinedicarboxylate
  参考文献：
  名称：

  Pyridostatin类化合物及其制备方法与应用

  摘要：

  本发明提供一种Pyridostatin化合物及其制备方法与应用。所述Pyridostatin化合物的结构式如式I所示。该化合物及其药学上可接受的盐对人肺癌和人结肠癌表现出好的抗肿瘤活性。

  公开号：

  CN104045629B

文献信息

• Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells
  作者：Sebastian Müller、Deborah A. Sanders、Marco Di Antonio、Stephanos Matsis、Jean-François Riou、Raphaël Rodriguez、Shankar Balasubramanian

  DOI：10.1039/c2ob25830g

  日期：——

  The synthesis, biophysical and biological evaluation of a series of G-quadruplex interacting small molecules based on a N,N′-bis(quinolinyl)pyridine-2,6-dicarboxamide scaffold is described. The synthetic analogues were evaluated for their ability to stabilize telomeric G-quadruplex DNA, some of which showed very high stabilization potential associated with high selectivity over double-stranded DNA. The compounds exhibited growth arrest of cancer cells with detectable selectivity over normal cells. Long-time growth arrest was accompanied by senescence, where telomeric dysfunction is a predominant mechanism together with the accumulation of restricted DNA damage sites in the genome. Our data emphasize the potential of a senescence-mediated anticancer therapy through the use of G-quadruplex targeting small molecules based on the molecular framework of pyridostatin.

  描述了一系列基于N,N′-双(喹啉基)吡啶-2,6-二羧酰胺支架的G-四链体相互作用小分子的合成、生物物理和生物学评估。这些合成的类似物被评估了其稳定端粒G-四链体DNA的能力，其中一些显示出很高的稳定潜力，并对双链DNA表现出很高的选择性。这些化合物在抑制癌细胞生长方面表现出可检测的选择性，且相对于正常细胞具有显著性。长期的生长抑制伴随着细胞衰老，其中端粒功能障碍是主要机制，同时伴有基因组内限制性DNA损伤位点的积累。我们的数据强调了通过使用基于吡啶斯塔丁分子框架的G-四链体靶向小分子，实施衰老介导的抗癌治疗的潜力。
• Pyridostatins selectively recognize two different forms of the human telomeric G-quadruplex structures and their anti-tumor activities in vitro
  作者：Li-Xia Wang、Qian Shang、Qian Li、Jun-Feng Xiang、Yan Liu、Ai-Jiao Guan、Hong-Xia Sun、Li-Jia Yu、Ya-Lin Tang

  DOI：10.1016/j.tet.2015.05.081

  日期：2015.7

  G-quadruplex as a therapeutic target to develop novel anti-cancer agents has attracted a growing interest. Among all the ligands of G-quadruplexes, pyridostatin derivatives play a very important role. Here, we first reported the recognition of the fundamental skeleton pyridostatin I, which was simply synthesized. Compared to pyridostatin II comprising terminal amino groups, pyridostatin I selectively stabilized intramolecular anti-parallel telomeric G-quadruplex by raising the melting temperature about 20 degrees C at 295 rim of H22, while pyridostatin II preferred to stabilize intermolecular parallel telomeric G-quadruplex by raising the melting temperature about 25 degrees C at 265 nm of H7, maybe due to the suited size measurements between G-quadruplex hosts and pyridostatin guests. MTT assays indicated that pyridostatin II had better cytotoxic effects against HCT-8 and A549 cell lines obviously, indicating positively charged side chains may be required for improving the water solubility and cellular uptake of the apolar central skeleton. (C) 2015 Published by Elsevier Ltd.
• A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA-Damage Response at Telomeres
  作者：Raphaël Rodriguez、Sebastian Müller、Justin A. Yeoman、Chantal Trentesaux、Jean-François Riou、Shankar Balasubramanian

  DOI：10.1021/ja805615w

  日期：2008.11.26

  We describe a novel synthetic small molecule which shows an unprecedented stabilization of the human telomeric G-quadruplex with high selectivity relative to double-stranded DNA. We report that this compound can be used in vitro to inhibit telomerase activity and to uncap human POT1 (protection of telomeres 1) from the telomeric G-overhang. We also show that the small molecule G-quadruplex binder induces a partial alteration of shelterin through POT1 uncapping from telomeres in human HT1080 cancer cells and the presence of gamma H2AX foci colocalized at telomeres.
• Stabilization of G-quadruplex DNA and inhibition of Bcl-2 expression by a pyridostatin analog
  作者：Yun Feng、Dazhang Yang、Hongbo Chen、Wenli Cheng、Lixia Wang、Hongxia Sun、Yalin Tang

  DOI：10.1016/j.bmcl.2016.02.065

  日期：2016.4

  The G-quadruplexes located in the P1 promoter of B-cell lymphoma-2 (Bcl-2) gene are implicated to regulate Bcl-2 expression. Here, we designed a new pyridostatin analog named PDF, which exhibited high specificity and stabilizing effect toward G-quadruplexes. The luciferase assay demonstrated that PDF could significantly suppress Bcl-2 transcriptional activation in human laryngeal squamous carcinoma cells (Hep-2) cells. Besides, PDF also induced cell apoptosis in vitro assays. These results provide an excellent G-quadruplex specific ligand as an efficient Bcl-2 inhibitor. These results also implicate that PDF may be a potential anticancer drug to head neck cancer. (C) 2016 Elsevier Ltd. All rights reserved.
• Pyridostatin类化合物及其制备方法与应用
  申请人：中国科学院化学研究所

  公开号：CN104045629B

  公开（公告）日：2016-03-02

  本发明提供一种Pyridostatin化合物及其制备方法与应用。所述Pyridostatin化合物的结构式如式I所示。该化合物及其药学上可接受的盐对人肺癌和人结肠癌表现出好的抗肿瘤活性。