Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B(2) receptor antagonists resulted in enhancing binding affinities for the human B(2) receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B(2) receptor but not for the guinea pig one. A series of 4-(1-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [(3)H]BK to the cloned human B(2) receptor expressed in Chinese hamster ovary cells with an IC(50) value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 microg/kg by intravenous administration.