3-(4-bromo-phenyl)-pyrano[3,4-c]pyridin-1-one | 1560949-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 3-(4-bromo-phenyl)-pyrano[3,4-c]pyridin-1-one
• 英文别名: 3-(4-Bromophenyl)pyrano[3,4-c]pyridin-1-one；3-(4-bromophenyl)pyrano[3,4-c]pyridin-1-one
• CAS: 1560949-48-5
• 化学式: C₁₄H₈BrNO₂
• 分子量: 302.127
• InChiKey: CRPSHNTVCXTCSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromo-phenyl)-pyrano[3,4-c]pyridin-1-one 在 ammonium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 3-(4-bromophenyl)-2H-[2,7]naphthyridin-1-one
  参考文献：
  名称：

  [EN] (AZA-)ISOQUINOLINONE DERIVATIVES
  [FR] DÉRIVÉS DE (AZA-)ISOQUINOLINONE

  摘要：

  公开号：

  WO2014023390A3
• 作为产物：
  描述：

  4-溴-3-氰基吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3-(4-bromo-phenyl)-pyrano[3,4-c]pyridin-1-one
  参考文献：
  名称：

  [EN] (AZA-)ISOQUINOLINONE DERIVATIVES
  [FR] DÉRIVÉS DE (AZA-)ISOQUINOLINONE

  摘要：

  公开号：

  WO2014023390A3

文献信息

• (AZA-)ISOQUINOLINONE DERIVATIVES
  申请人：MERCK PATENT GMBH

  公开号：US20150210686A1

  公开（公告）日：2015-07-30

  Compounds of the formula I in which R 1 , X, Y and n have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

  公式I的化合物，其中R1、X、Y和n具有Claim1中指示的含义，是Tankyrase的抑制剂，可用于治疗癌症、心血管疾病、中枢神经系统损伤和不同形式的炎症等疾病。
• Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
  作者：Katerina Kumpan、Amit Nathubhai、Chenlu Zhang、Pauline J. Wood、Matthew D. Lloyd、Andrew S. Thompson、Teemu Haikarainen、Lari Lehtiö、Michael D. Threadgill

  DOI：10.1016/j.bmc.2015.05.005

  日期：2015.7

  The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl) ate their target proteins using NAD(+) as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with beta-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused > 1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2. (C) 2015 Elsevier Ltd. All rights reserved.
• US9376433B2
  申请人：——

  公开号：US9376433B2

  公开（公告）日：2016-06-28