1-(Carboxybenzyl)imidazole-5-acrylic acids: potent and selective angiotensin II receptor antagonists

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…However, canine data were excluded from this figure, because in multiple dog tissues AT1R affinities for multiple ARBs are lower than in the same tissues from other mammals (de Gasparo and Whitebread, 1995). Data are pK i or, in approximation thereof, pIC 50 values as reported in (Chiu et al, ,b,c, 1992Speth and Kim, 1990;Wong et al, 1990b,d;Buhlmayer et al, 1991;Obermüller et al, 1991;Weinstock et al, 1991;Aguilera, 1992;Boulay et al, 1992;Crawford et al, 1992;Edwards et al, 1992a,b;Ernsberger et al, 1992;Leung et al, 1992;Lin et al, 1992;Lyall et al, 1992;Noda et al, 1993Noda et al, , 1996Ouali et al, 1992;Wienen et al, 1992Wienen et al, ,1993Bernhart et al, 1993;Cazaubon et al, 1993;Criscione et al, 1993;Feolde et al, 1993;Ries et al, 1993;Shibouta et al, 1993;Tanabe et al, 1993;Dickinson et al, 1994;Herbert et al, 1994;Nishikawa et al, 1994;Schambye et al, 1994Schambye et al, ,1995Nakamura et al, 1994;Wienen and Entzeroth, 1994;de Gasparo and Whitebread, 1995;Feng et al, 1995;Flesch et al, 1995;Itazaki et al, 1995;Keiser et al, 1995;…”

AT1 receptor characteristics of angiotensin analogue binding in human synovium

“…Binding to each structure was of high affinity, and no significant differences were found between structures in association and dissociation rates, nor in Kd values (Table 2). (Whitebread et al, 1989;Dudley et al, 1990;Weinstock et al, 1991;Bottari et al, 1991 (Urata et al, 1989) and on cultured vascular smooth muscle cells (Whitebread et al, 1989) and are believed to mediate vasoconstriction (Chiu et al, 1990) and smooth muscle hypertrophy (Millet et al, 1992), both of which may reduce tissue perfusion. Synovial hypoperfusion has been implicated in the pathogenesis of human arthritis (Levick, 1990), and the potential of AT, antagonists to enhance tissue perfusion (Azuma et al, 1992) (Whitebread et al, 1989;Patel et al, 1989).…”

Angiotensin II receptor pharmacology and AT1-receptor blockers

“…19 Despite the fact that losartan binding to the AT 1 receptor is sufficient to result in an effective receptor blockade, it is lower when compared to some other AT 1 antagonists, whose IC 50 values range from 1.5 to 4 nmol/L. 21,26,93,94 However, the binding affinity of EXP3174 ( IC 50 of 3.7 nmol/L), 19 is substantially higher, and is within the range of other AT 1 antagonists. The affinity of EXP3174 for the AT 1 receptor is 30 000-fold higher than that for the AT 2 receptor.…”