3-cyano-2-(4-trifluoromethylphenylethynyl)pyridine | 1613435-69-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-cyano-2-(4-trifluoromethylphenylethynyl)pyridine
• 英文别名: 2-[2-[4-(Trifluoromethyl)phenyl]ethynyl]pyridine-3-carbonitrile；2-[2-[4-(trifluoromethyl)phenyl]ethynyl]pyridine-3-carbonitrile
• CAS: 1613435-69-0
• 化学式: C₁₅H₇F₃N₂
• 分子量: 272.229
• InChiKey: XBXZFVTXZWTOGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-cyano-2-(4-trifluoromethylphenylethynyl)pyridine 在 硫酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 1-methyl-5-oxo-7-(4-trifluoromethylphenyl)-5,6-dihydro-1,6-naphthyridin-1-ium iodide
  参考文献：
  名称：

  [EN] TANKYRASE INHIBITORS
  [FR] INHIBITEURS DE TANKYRASE

  摘要：

  本发明涉及一种具有式I的化合物，其中X为C(R6)或N，Y为C或N，环A、环B、R1和R2具有本文中定义的含义，前提是当环B为碳环时，X为C(R6)；或其药学上可接受的盐或溶剂。这些化合物是坦克酶-1和坦克酶-2抑制剂，并可用于治疗多种疾病，包括癌症。

  公开号：

  WO2014087165A1
• 作为产物：
  描述：

  1-[(三甲基硅基)乙炔基]-4-(三氟甲基)苯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 sodium ascorbate 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 136.5h， 生成 3-cyano-2-(4-trifluoromethylphenylethynyl)pyridine
  参考文献：
  名称：

  Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2015.05.005

文献信息

• A unified approach to benzo[<i>c</i>]phenanthridines <i>via</i> the cascade dual-annulation/formylation of 2-alkynyl/alkenylbenzonitriles
  作者：Shalini Verma、Manoj Kumar、Akhilesh K. Verma

  DOI：10.1039/d3cc00197k

  日期：——

  A base-mediated versatile cascade dual-annulation and formylation of 2-alkenyl/alkynylbenzonitriles with 2-methylbenzonitriles has been established for the construction of four different classes of amino and amido substituted benzo[c]phenanthridines and benzo[c]phenanthrolines. The synthesized molecules could be of utmost relevance in pharmaceuticals. The transformation uses the solvent DMF as the

  已经建立了碱基介导的多功能级联双环化和 2-烯基/炔基苯甲腈与 2-甲基苯甲腈的甲酰化，用于构建四种不同类别的氨基和酰氨基取代的苯并 [c] 菲啶和苯并 [c]菲咯啉。合成的分子可能在药物中具有最大的相关性。该转化使用溶剂 DMF 作为甲酰源，用于合成酰胺基取代的支架。这种无过渡金属的独特策略能够在室温下在一个锅中形成多个 C-C 和 C-N 键。