Identification of a Nonpeptidic and Conformationally Restricted Bradykinin B1 Receptor Antagonist with Anti-Inflammatory Activity

Citations Over TimeTop 17% of 2007 papers

Abstract

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., 28 decreased plasma extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed approximately 30% of the gained affinity between "flexible" 4 (Ki = 132 nM) and "rigid" 28 (Ki = 0.77 nM) to decreased conformational entropy.

Related Papers

• → The role of bradykinin B₁ receptors in the maintenance of intra‐articular plasma extravasation in chronic antigen‐induced arthritis(1994)83 cited
• → Role of peptidases and NK1 receptors in vascular extravasation induced by bradykinin in rat nasal mucosa(1993)30 cited
• → Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase(1992)22 cited
• → Tachyphylaxis develops to bradykinin-induced plasma extravasation in the rat(1996)2 cited
• → Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase(1993)7 cited