Quantitative structure-activity relationships (QSAR) of 4-amino-2,6-diarylpyrimidine-5-carbonitriles with anti-inflammatory activity

• Autor(a) principal: Silva,João Bosco P. da
• Data de Publicação: 2008
• Outros Autores: Ramos,Mozart N., Barros Neto,Benício de, Melo,Sebastião José de, Falcão,Emerson Peter da Silva, Catanho,Maria Teresa J. de Almeida
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532008000200021
• topic: pyrimidine derivatives; anti-inflammatory activity; molecular modeling; QSAR

The experimental anti-inflammatory activities of eight 4-amino-2,6-diarylpyrimidine-5-carbonitriles were subjected to a QSAR analysis based on results from B3LYP/6-31G(d,p) and AM1 electronic structure calculations. Principal component analyses and regressions based on these data indicate that potentially more active compounds should have low dipole moment and partition coefficient values and also be affected by the values of the charges of the carbon atoms through which the two aromatic rings are bonded to the pyrimidinic ring. Two new molecules were predicted to be at least as active as those with the highest activities used in the model building stage. One of them, having a methoxy group attached to one of the aromatic rings, was predicted to have an anti-inflammatory activity value of 52.3%. This molecule was synthesized and its experimental activity was found to be 52.8%, in agreement with the AM1 theoretical prediction. This value is 5% higher than the largest value used for modeling.