Synthesis of new derivatives of 8-OH-DPAT: influence of substitution on the aromatic ring on the pharmacological profile

Abstract Several new derivatives of 8-OH-DPAT were prepared by a new synthetic route using the Curtius degradation of 2-tetralin carboxylic acid derivatives. Their affinity for 5-HT 1A and 5-HT 1B receptors was evaluated in binding assays with rat hippocampus and striatum respectively. The results emphasized the favorable effect of the substitution on the phenyl ring of a homocyclic ring fused in positions [6,7] or [6,5] to obtain specific ligands for the 5-HT 1B receptor. Methyl substitution in position 5 gave a compound with good affinity for the 5-HT 1A receptor and preliminary pharmacological assays an antagonist profile for this compound.