Benzodiazepines as Potent and Selective Bradykinin B1 Antagonists
dataset
posted on 2003-04-03, 00:00 authored by Michael R. Wood, June J. Kim, Wei Han, Bruce D. Dorsey, Carl F. Homnick, Robert M. DiPardo, Scott D. Kuduk, Tanya MacNeil, Kathy L. Murphy, Edward V. Lis, Richard W. Ransom, Gary L. Stump, Joseph J. Lynch, Stacey S. O'Malley, Patricia J. Miller, Tsing-Bau Chen, Charles M. Harrell, Raymond S. L. Chang, Punam Sandhu, Joan D. Ellis, Peter J. Bondiskey, Douglas J. Pettibone, Roger M. Freidinger, Mark G. BockAntagonism 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
(Ki = 0.59 nM) and high selectivity against the bradykinin B2
receptor (Ki > 10 μM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent
hyperalgesia model.
