具有支气管扩张活性的4H-吡喃并[3,2-c]吡啶-3-腈的合成、生物测定及定量构效关系研究
Synthesis, bioassay, and QSAR study of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles.
作者信息
Girgis Adel S, Saleh Dalia O, George Riham F, Srour Aladdin M, Pillai Girinath G, Panda Chandramukhi S, Katritzky Alan R
机构信息
Pesticide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
出版信息
Eur J Med Chem. 2015 Jan 7;89:835-43. doi: 10.1016/j.ejmech.2013.12.032. Epub 2014 Jan 3.
A statistically significant QSAR model describing the bioactivity of bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles (N = 41, n = 8, R(2) = 0.824, R(2)cv = 0.724, F = 18.749, s(2) = 0.0018) was obtained employing CODESSA-Pro software. The bronchodilatory active 4H-pyrano[3,2-c]pyridine-3-carbonitriles 17-57 were synthesized through a facile approach via reaction of 1-alkyl-4-piperidones 1-4 with ylidenemalononitriles 5-16 in methanol in the presence of sodium. The bronchodilation properties of 17-57 were investigated in vitro using isolated guinea pig tracheal rings pre-contracted with histamine (standard method) and compared with theophylline (standard reference). Most of the compounds synthesized exhibit promising bronchodilation properties especially, compounds 25 and 28.
使用CODESSA-Pro软件获得了一个具有统计学意义的定量构效关系（QSAR）模型，该模型描述了具有支气管扩张活性的4H-吡喃并[3,2-c]吡啶-3-腈的生物活性（N = 41，n = 8，R(2) = 0.824，R(2)cv = 0.724，F = 18.749，s(2) = 0.0018）。通过1-烷基-4-哌啶酮1-4与亚甲基丙二腈5-16在甲醇中于钠存在下的简便反应方法，合成了具有支气管扩张活性的4H-吡喃并[3,2-c]吡啶-3-腈17-57。使用预先用组胺预收缩的豚鼠离体气管环（标准方法）体外研究了17-57的支气管扩张特性，并与茶碱（标准对照）进行了比较。合成的大多数化合物表现出有前景的支气管扩张特性，特别是化合物25和28。
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