Comfa Study of A Series of N1-(Substituted)Aryl-2-(Substituted)-5,7-Dimethylpyrido[ 2,3-D]Pyrimidin-4(3h)-One – Histamine H1-Receptor Antagonists

Abstract

In continuation of our efforts to develop a potent and selective peripheral H1 receptor antagonist for the treatment of allergic rhinitis or urticaria, earlier, we reported potent H1-receptor antagonistic activity in a series of N1-(substituted)aryl-2-(substituted)-5,7-dimethyl pyrido[2,3-d]pyrimidin-4(3H)-one. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies were performed on H1 receptor antagonists based on Comparative Molecular Field Analysis (CoMFA) method. Significant correlation coefficients, r2 = 0.894 and q2 = 0.491 were obtained and the generated model was externally validated using test sets with r2 predicted 0.624. The CoMFA model can be used to design novel, potent and selective H1 receptor antagonists prior to their synthesis.