Structure-affinity relationship studies on benzotriazole derivatives binding to 5-HT receptor subtypes

Article abstract of DOI:10.1016/0223-5234(96)89136-7

A number of benzotriazole derivatives have been assayed in radioligand binding experiments involving the following recombinant human serotonin receptors: 5-HT(2A), 5-HT(1A), 5-HT(1Dβ) and 5-HT(2C). Several of the compounds tested show interesting selectivity profiles. In particular, the affinities of 3d, 4a and 4d for the 5-HT(2A) subtype (with pK(i) values of 7.4, 7.4 and 8.0, respectively) are between 100 and 1000 times higher than for the other investigated receptors. Compound 5l, characterized by a pK(i) value of 7.4 on the 5-HT(1A) receptor, binds with 100- to 1000-fold lower potencies on the other receptors. Our benzotriazole derivatives are generally weak ligands of the 5-HT(1Dβ) and 5-HT(2C) receptors. Structure-affinity relationship data suggest that not all the compounds exhibit the same binding mode at the 5-HT(2A) and 5-HT(1A) receptors.