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Identification of a nonpeptidic and conformationally restricted bradykinin B1 receptor antagonist with anti-inflammatory activity.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

D'Amico DC,Aya T,Human J,Fotsch C,Chen JJ,Biswas K,Riahi B,Norman MH,Willoughby CA,Hungate R,Reider PJ,Biddlecome G,Lester-Zeiner D,Staden CV,Johnson E,Kamassah A,Arik L,Wang J,Viswanadhan VN,Groneberg RD,Zhan J,

doi

10.1021/jm061224g

subject

Has Abstract

pub_date

2007-02-22 00:00:00

pages

607-10

issue

4

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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