STRUCTURE-AFFINITY RELATIONSHIP STUDIES ON BENZOTRIAZOLE DERIVATIVES BINDING TO 5-HT RECEPTOR SUBTYPES

A number of benzotriazole derivatives have been assayed in radioligand binding experiments involving the following recombinant human seroton in receptors: 5-HT2A, 5-HT1A, 5-HT1d beta and 5-HT2C. Several of the c ompounds tested show interesting selectivity profiles. In particular, the affinities of 3d, 4a and 4d for the 5-HT2A subtype (with pK(i) val ues of 7.4, 7.4 and 8.0, respectively) are between 100 and 1000 times higher than for the other investigated receptors. Compound 51, charact erized by a pK(i) value of 7.4 on the 5-HT1A receptor, binds with 100- to 1000-fold lower potencies on the other receptors. Our benzotriazol e derivatives are generally weak ligands of the 5-HT1D beta and 5-HT2C receptors. Structure-affinity relationship data suggest that not all the compounds exhibit the same binding mode at the 5-HT2A and 5-HT1A r eceptors.