Indole-2-carboxamides as allosteric modulators of the cannabinoid CB₁ receptor.

We synthesized new N-phenylethyl-1H-indole-2-carboxamides as the first SAR study of allosteric modulators of the CB(1) receptor. The presence of the carboxamide functionality was required in order to obtain a stimulatory effect. The maximum stimulatory activity on CB(1) was exerted by carboxamides 13 (EC(50) = 50 nM) and 21 (EC(50) = 90 nM) bearing a dimethylamino or piperidinyl group, respectively, at position 4 of the phenethyl moiety and a chlorine atom at position 5 of the indole.