ChemInform Abstract: 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.

Abstract

Abstract Anumber 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-HT 1A receptors. 5-HT 1A, 5-HT 2A and 5-HT 2C 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 α 1 , α 2 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-HT 1A receptor binding site. Three derivatives 2c , 3c and 3e bind to 5-HT 1A receptors in the nanomolar range (IC 50 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 1h and 4c are new selective ligands for 5-HT 2A (IC 50 = 89 nM) and 5-HT 2C receptors (IC 50 = 17 nM), respectively.