6-(1,3-benzodioxol-5-yl)-4-(thiophen-2-yl)-2-oxo-1,2-dihydropyridin-3-carbonitrile | 1189115-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 6-(1,3-benzodioxol-5-yl)-4-(thiophen-2-yl)-2-oxo-1,2-dihydropyridin-3-carbonitrile
• 英文别名: 6-(1,3-benzodioxol-5-yl)-2-oxo-4-thiophen-2-yl-1H-pyridine-3-carbonitrile
• CAS: 1189115-20-5
• 化学式: C₁₇H₁₀N₂O₃S
• 分子量: 322.344
• InChiKey: XVOLXPZTLLUULE-UHFFFAOYSA-N

物化性质

• 熔点：
  312-314 °C(Solv: N,N-dimethylformamide (68-12-2); ethanol (64-17-5))
• 沸点：
  580.6±50.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  99.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-噻吩甲醛 、 3,4-亚甲二氧苯乙酮 、 氰乙酸乙酯 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 以70%的产率得到6-(1,3-benzodioxol-5-yl)-4-(thiophen-2-yl)-2-oxo-1,2-dihydropyridin-3-carbonitrile
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors

  摘要：

  Two series of 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles were synthesized through a combinatorial approach. The prepared analogues were evaluated for their in vitro capacity to inhibit PDE3A and the growth of the human HT-29 colon adenocarcinoma tumor cell line. Compound 6-(4-bromophenyl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (Id) exhibited the strongest PDE3 inhibition when cGMP but not cAMP is the substrate with a IC50 of 27 mu M, which indicates a highly selective mechanism of enzyme inhibition. On the other hand, compound 6-(1,3-benzodioxol-5-yl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (Ii) was the most active in inhibiting colon tumor cell growth with a IC50 of 3 mu M. The electronic effects, steric effects and conformational aspects of Id seem to be the most crucial for the PDE3 inhibition. Meanwhile, steric factors and the H-bonding capability seem to be the most important factors for tumor cell growth inhibitory activity. Conversely, there is no direct correlation between PDE3 inhibition and anticancer activity for the prepared compounds. An in silico docking experiment indicates the potential involvement of other potential molecular targets such as PIM-1 kinase to explain its tumor cell growth inhibitory activity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.063

文献信息

• Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors
  作者：Ashraf H. Abadi、Tamer M. Ibrahim、Khaled M. Abouzid、Jochen Lehmann、Heather N. Tinsley、Bernard D. Gary、Gary A. Piazza

  DOI：10.1016/j.bmc.2009.06.063

  日期：2009.8

  Two series of 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles were synthesized through a combinatorial approach. The prepared analogues were evaluated for their in vitro capacity to inhibit PDE3A and the growth of the human HT-29 colon adenocarcinoma tumor cell line. Compound 6-(4-bromophenyl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (Id) exhibited the strongest PDE3 inhibition when cGMP but not cAMP is the substrate with a IC50 of 27 mu M, which indicates a highly selective mechanism of enzyme inhibition. On the other hand, compound 6-(1,3-benzodioxol-5-yl)-4-(2-ethoxyphenyl)-2-imino-1,2-dihydropyridine-3-carbonitrile (Ii) was the most active in inhibiting colon tumor cell growth with a IC50 of 3 mu M. The electronic effects, steric effects and conformational aspects of Id seem to be the most crucial for the PDE3 inhibition. Meanwhile, steric factors and the H-bonding capability seem to be the most important factors for tumor cell growth inhibitory activity. Conversely, there is no direct correlation between PDE3 inhibition and anticancer activity for the prepared compounds. An in silico docking experiment indicates the potential involvement of other potential molecular targets such as PIM-1 kinase to explain its tumor cell growth inhibitory activity. (C) 2009 Elsevier Ltd. All rights reserved.