Chromenones as potent bradykinin B1 antagonists

A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chloroch...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-01, Vol.22 (1), p.619-622
Hauptverfasser:	Bryan, Marian C., Biswas, Kaustav, Peterkin, Tanya A.N., Rzasa, Robert M., Arik, Leyla, Lehto, Sonya G., Sun, Hong, Hsieh, Feng-Yin, Xu, Cen, Fremeau, Robert T., Allen, Jennifer R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals antagonists Benzopyrans - chemical synthesis Benzopyrans - pharmacology Biological and medical sciences bradykinin Bradykinin B1 receptor Bradykinin B1 Receptor Antagonists Carrageenan - pharmacology chemistry Chemistry, Pharmaceutical - methods Chromenone Chronic Pain - drug therapy Drug Design Humans Hyperalgesia - drug therapy Inflammatory pain Inhibitory Concentration 50 Kinetics Medical sciences Models, Chemical pain pharmacokinetics Pharmacology. Drug treatments Rabbits Structure-Activity Relationship Tumor Necrosis Factor-alpha - metabolism
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Zusammenfassung:	A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.10.068