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We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4−17 nM). At 90 mg/kg s.c., 28decreased plasma extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed ∼30% of the gained affinity between “flexible” 4(Ki132 nM) and “rigid” 28(Ki0.77 nM) to decreased conformational entropy. [ABSTRACT FROM AUTHOR]