3,5-Dimethoxy-2-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenol | 190973-16-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,5-Dimethoxy-2-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenol
• 英文别名: 3,5-dimethoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenol
• CAS: 190973-16-1
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: HZJYPUWBNHUNDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-Dimethoxy-2-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenol 在 吡啶 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 生成 2-acetyl-3,5-dimethoxy-6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl 3-chlorobenzoate
  参考文献：
  名称：

  Structure–activity relationship studies of flavopiridol analogues

  摘要：

  Cyclin dependent kinases (CDKs) along with the complementary cyclins form key regulatory checkpoint controls on the cell cycle. Flavopiridol is a synthetic flavone that shows potent and selective cyclin-dependent kinase inhibitory activity. In this paper, we report modifications of the 3-hydroxy-1-methylpiperidinyl (D ring) of flavopiridol and their effect on CDK inhibitory activity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00156-6
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 、 3,5-二甲氧基苯酚 在 盐酸 、 溶剂黄146 作用下， 以50%的产率得到3,5-Dimethoxy-2-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenol
  参考文献：
  名称：

  鉴定出一系列新的类黄酮吡啶醇样结构作为具有高细胞毒性潜能的激酶抑制剂。

  摘要：

  在这项工作中，已经制备了带有硫糖，氨基酸和主要通过其C环上的硫醚和胺键与黄酮哌啶醇相连的杂环部分的独特的黄酮哌啶类似物。带有硫醚-苯并咪唑作为取代基的类似物在体外已显示出对多达七种癌细胞系的高细胞毒活性。它们的细胞毒性作用与黄酮哌啶醇相当。由结构-活性关系（SAR）研究和计算机对接产生的活性最高的化合物13c显示出最佳的抗增殖活性，并且比参考化合物更有效。此外，化合物13c对CDK9，CDK10和GSK3β蛋白激酶显示出显着的纳摩尔抑制作用。

  DOI：

  10.1016/j.ejmech.2020.112355

文献信息

• Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site
  作者：Laura J. Hampson、Catherine Arden、Loranne Agius、Minas Ganotidis、Magda N. Kosmopoulou、Costas Tiraidis、Yiannis Elemes、Constantinos Sakarellos、Demetres D. Leonidas、Nikos G. Oikonomakos

  DOI：10.1016/j.bmc.2006.07.060

  日期：2006.12

  The bioactivity in hepatocytes of glycogen phosphorylase inhibitors that bind to the active site, the allosteric activator site and the indole carboxamide site has been described. However, the pharmacological potential of the purine nucleoside inhibitor site has remained unexplored. We report the chemical synthesis and bioactivity in hepatocytes of four new olefin derivatives of flavopiridol (1-4) that bind to the purine site. Flavopiridol and 1-4 counteracted the activation of phosphorylase in hepatocytes caused by AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), which is metabolised to an AMP analogue. Unlike an indole carboxamide inhibitor, the analogues I and 4 suppressed the basal rate of glycogenolysis in hepatocytes by allosteric inhibition rather than by inactivation of phosphorylase, and accordingly caused negligible stimulation of glycogen synthesis. However, they counteracted the stimulation of glycogenolysis by dibutyryl cAMP by both allosteric inhibition and inactivation of phosphorylase. Cumulatively, the results show key differences between purine site and indole carboxamide site inhibitors in terms of (i) relative roles of dephosphorylation of phosphorylase-a as compared with allosteric inhibition, (ii) counteraction of the efficacy of the inhibitors on glycogenolysis by dibutyryl-cAMP and (iii) stimulation of glycogen synthesis. (c) 2006 Elsevier Ltd. All rights reserved.
• Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency
  作者：Nada Ibrahim、Pascal Bonnet、Jean-Daniel Brion、Jean-François Peyrat、Jerome Bignon、Helene Levaique、Béatrice Josselin、Thomas Robert、Pierre Colas、Stéphane Bach、Samir Messaoudi、Mouad Alami、Abdallah Hamze

  DOI：10.1016/j.ejmech.2020.112355

  日期：2020.8

  In this work, unique flavopiridol analogs bearing thiosugars, amino acids and heterocyclic moieties tethered to the flavopiridol via thioether and amine bonds mainly on its C ring have been prepared. The analogs bearing thioether-benzimidazoles as substituents have demonstrated high cytotoxic activity in vitro against up to seven cancer cell lines. Their cytotoxic effects are comparable to those of

  在这项工作中，已经制备了带有硫糖，氨基酸和主要通过其C环上的硫醚和胺键与黄酮哌啶醇相连的杂环部分的独特的黄酮哌啶类似物。带有硫醚-苯并咪唑作为取代基的类似物在体外已显示出对多达七种癌细胞系的高细胞毒活性。它们的细胞毒性作用与黄酮哌啶醇相当。由结构-活性关系（SAR）研究和计算机对接产生的活性最高的化合物13c显示出最佳的抗增殖活性，并且比参考化合物更有效。此外，化合物13c对CDK9，CDK10和GSK3β蛋白激酶显示出显着的纳摩尔抑制作用。
• Structure–activity relationship studies of flavopiridol analogues
  作者：Krishna K. Murthi、Marja Dubay、Christopher McClure、Leonardo Brizuela、Michael D. Boisclair、Peter J. Worland、Muzammil M. Mansuri、Kollol Pal

  DOI：10.1016/s0960-894x(00)00156-6

  日期：2000.5

  Cyclin dependent kinases (CDKs) along with the complementary cyclins form key regulatory checkpoint controls on the cell cycle. Flavopiridol is a synthetic flavone that shows potent and selective cyclin-dependent kinase inhibitory activity. In this paper, we report modifications of the 3-hydroxy-1-methylpiperidinyl (D ring) of flavopiridol and their effect on CDK inhibitory activity. (C) 2000 Elsevier Science Ltd. All rights reserved.