189268-91-5Relevant academic research and scientific papers
A New Series of Highly Potent Non-Peptide Bradykinin B2 Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference
Sawada, Yuki,Kayakiri, Hiroshi,Abe, Yoshito,Imai, Keisuke,Mizutani, Tsuyoshi,Inamura, Noriaki,Asano, Masayuki,Aramori, Ichiro,Hatori, Chie,Katayama, Akira,Oku, Teruo,Tanaka, Hirokazu
, p. 1617 - 1630 (2007/10/03)
Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B2 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 B2 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 [ 3H]BK to the cloned human B2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 μg/kg by intravenous administration.
