Joacy C. Aguiar

Understanding DP receptor antagonism using a CoMSIA approach

A Comparative Molecular Similarity Indices Analysis (CoMSIA) was performed for 2,6-substituted-4-monosubstituted aminopyrimidine antagonists of prostaglandin D(2) receptor (DP). Both two-component (Q(2) = 0.63, R(2) = 0.82, SEE = 0.47 pIC(50)) and three-component (Q(2) = 0.70, R(2) = 0.91, SEE = 0.36 pIC(50)) CoMSIA models were established. Two hydrogen-bond acceptors with spatial separation of about 8Å are shown as optimal for binding. A large hydrophobic center that separates the two acceptors confers to the potency of the 2,6-substituted-4-monosubstituted aminopyrimidine. The models were used to predict IC(50) values for compounds which had functional groups different from those in the training set.