2-phenyl-5,7-dimethoxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4H-benzopyran-4-one | 916888-62-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-phenyl-5,7-dimethoxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4H-benzopyran-4-one
• 英文别名: 5,7-dimethoxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-phenyl-4H-chromen-4-one；5,7-dimethoxy-8-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-phenylchromen-4-one
• CAS: 916888-62-5
• 化学式: C₂₃H₂₃NO₄
• 分子量: 377.44
• InChiKey: DYTJDRKEZOMJLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-phenyl-5,7-dimethoxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4H-benzopyran-4-one 在 吡啶盐酸盐 作用下， 生成 2-phenyl-5,7-dihydroxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4H-benzopyran-4-one
  参考文献：
  名称：

  Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.07.060
• 作为产物：
  描述：

  (E)-1-(2-hydroxy-4,6-dimethoxy-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-phenylprop-2-en-1-one 在 硫酸 、 碘 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 以50%的产率得到2-phenyl-5,7-dimethoxy-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4H-benzopyran-4-one
  参考文献：
  名称：

  [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER
  [FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER

  摘要：

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。

  公开号：

  WO2010129858A1

文献信息

• COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR TREATING CANCER
  申请人：Xu Wen Fang

  公开号：US20120121692A1

  公开（公告）日：2012-05-17

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用于作为抗肿瘤剂的化合物，其中所披露的化合物用于制备用于治疗癌症的药物，治疗肿瘤的方法包括向受试者投与含有所披露的细胞毒性药物之一或多个的组合物，以及制备所披露的抗肿瘤剂的方法。
• 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.
• COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER
  申请人：Georgia State University Research Foundation, Inc.

  公开号：EP2429292A1

  公开（公告）日：2012-03-21
• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• 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.