SR 141716A is a biarylpyrazole compound which has been considered for many years as the prototypical cannabinoid (CB) receptor antagonist. Some very close structural relatives of SR 141716A were recently prepared and tested for their ability to act as antagonists of the CB1 receptor. AM251 is one of these analogs, wherein the p-chloro group attached to the phenyl substituent at C-5 of the pyrazole ring is replaced with a p-iodo group. The resulting compound exhibits slightly better binding affinity for the CB1 receptor with a Ki value of 7.5 nM compound to SR 141716A, which has a Ki value of 11.5 nM. However AM251 is about two-fold more selective for the CB1 receptor when compared to SR 141716A.
