SR 141716A is a biarylpyrazole compound which has been considered for many years as the prototypical cannabinoid (CB) receptor antagonist.¹ Some very close structural relatives of SR 141716A were recently prepared and tested for their ability to act as antagonists of the CB₁ receptor.² 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 K_i value of 7.5 nM compound to SR 141716A, which has a K_i value of 11.5 nM. However AM251 is about two-fold more selective for the CB₁ receptor when compared to SR 141716A.²

1 Rinaldi-Carmona, M., Barth, F., Héaulme, M., et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350 240-244 (1994).

2 Lan, R., Liu, Q., Fan, P., et al. Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J Med Chem 42 769-776 (1999).

Rinaldi-Carmona, M., Barth, F., Héaulme, M., et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350 240-244 (1994).

Lan, R., Liu, Q., Fan, P., et al. Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J Med Chem 42 769-776 (1999).

AM251 is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)