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 (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.