Three-dimensional pharmacophore models were generated for AT1 and ET(A) 
receptors based on highly selective AT1 and ET(A) antagonists using the program 
Catalyst/HipHop. Both the best pharmacophore model for selective AT1 antagonists 
(Hypo-AT(1)-7) and ETA antagonists (Hypo-ET(A)-1) were obtained through a 
careful validation process. All five features contained in Hypo-AT(1)-7 and 
Hypo-ET(A)-1 (hydrogen-bond acceptor (A), hydrophobic aliphatic (Z), negative 
ionizable (N), ring aromatic (R), and hydrophobic aromatic (Y)) seem to be 
essential for antagonists in terms of binding activity. Dual AT1 and ET(A) 
receptor antagonists (DARAs) can map to both Hypo-AT(1)-7 and Hypo-ET(A)-1, 
separately. Comparison of Hypo-AT(1)-7 and Hypo-ET(A)-1, not only AT1 and ET(A) 
antagonist pharmacophore models consist of essential features necessary for 
compounds to be highly active and selective toward their corresponding receptor, 
but also have something in common. The results in this study will act as a 
valuable tool for designing and researching structural relationship of novel 
dual AT1 and ET(A) receptor antagonists.