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Identification of a nonpeptidic and conformationally restricted bradykinin B1 receptor antagonist with anti-inflammatory activity.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2007 Feb 22; Vol. 50 (4), pp. 607-10. Date of Electronic Publication: 2007 Jan 23. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics
Anti-Inflammatory Agents, Non-Steroidal pharmacology
CHO Cells
Capillary Permeability drug effects
Chlorocebus aethiops
Chromans pharmacokinetics
Chromans pharmacology
Cricetinae
Cricetulus
Crystallography, X-Ray
Entropy
Humans
In Vitro Techniques
Models, Molecular
Molecular Conformation
Pleurisy drug therapy
Rabbits
Rats
Species Specificity
Stereoisomerism
Structure-Activity Relationship
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Bradykinin B1 Receptor Antagonists
Chromans chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 50
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17243660
- Full Text :
- https://doi.org/10.1021/jm061224g