Synthesis and binding affinities for 5-HT1A, 5-HT2A and 5-HT2C receptors of a series of 1-and 2-(4-arylpiperazinylalkyl)-4-(benzoyl)-1,2,3-triazole derivatives

A number of 1- and 2-(4-arylpiperazinylalkyl)-4-(benzoyl)-1,2,3-triazole derivatives (1-4) were prepared in order to obtain compounds with a high affinity and selectivity for 5-HT1A receptors. 5-HT1A, 5-HT2A and 5-MT2C affinities were determined by radioligand binding experiments and the most active compounds were also tested for binding affinities on dopaminergic D-1, D-2 and adrenergic a,, a, receptors. The modification of aromatic substituents, the length of the alkyl chain and its position on the 4-benzoyl-1,2,3-triazole ring were explored. Most of the considered compounds generally showed moderate to high affinity for the 5-HT1A receptor binding site. Three derivatives 2c, 3c and 3e bind to 5-HT1A receptors in the nanomolar range (IC50 values = 2, 7.2 and 2.6 nM respectively). The most active compound, 2c, presented a high degree of selectivity versus all considered receptors. It was found that the benzoyltriazole derivatives Ih and 4c are new selective ligands for 5-HT2A (IC50 = 89 nM) and 5-HT2C receptors (IC50 = 17 nM), respectively. (C) 1999 Editions scientifiques et medicales Elsevier SAS.