Benzodiazepines as Potent and Selective Bradykinin B1 Antagonists

Antagonism of the bradykinin B1 receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B1 receptor (K i = 0.59 nM) and high selectivity against the bradykinin B2 receptor (K i...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2003-05, Vol.46 (10), p.1803-1806
Hauptverfasser:	Wood, Michael R, Kim, June J, Han, Wei, Dorsey, Bruce D, Homnick, Carl F, DiPardo, Robert M, Kuduk, Scott D, MacNeil, Tanya, Murphy, Kathy L, Lis, Edward V, Ransom, Richard W, Stump, Gary L, Lynch, Joseph J, O'Malley, Stacey S, Miller, Patricia J, Chen, Tsing-Bau, Harrell, Charles M, Chang, Raymond S. L, Sandhu, Punam, Ellis, Joan D, Bondiskey, Peter J, Pettibone, Douglas J, Freidinger, Roger M, Bock, Mark G
Format:	Artikel
Sprache:	eng
Schlagworte:	Analgesics Animals Benzodiazepines - chemical synthesis Benzodiazepines - chemistry Benzodiazepines - pharmacology Biological and medical sciences Bradykinin Receptor Antagonists CHO Cells Cricetinae Humans Hyperalgesia - chemically induced Hyperalgesia - drug therapy Medical sciences Neuropharmacology Pharmacology. Drug treatments Radioligand Assay Rats Rats, Sprague-Dawley Receptor, Bradykinin B1 Receptor, Bradykinin B2 Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Antagonism of the bradykinin B1 receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B1 receptor (K i = 0.59 nM) and high selectivity against the bradykinin B2 receptor (K i > 10 μM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm034020y