Synthesis and in-vitro pharmacological evaluation of new 5-HT1A receptor ligands containing a benzotriazinone nucleus

Article abstract of DOI:10.1002/ardp.200700151

This paper reports the microwave-assisted synthesis and the binding assays on the 5-HT_1A, 5-HT_2A and 5-HT_2C receptors of new benzotriazinone derivatives, in order to identify selective ligands for the 5-HT_1A subtype receptor. Conventional and microwave heating of the reactions were compared. Good yields and short reaction times are the main advantages of our synthetic route. More active compounds were selected and further evaluated for their binding affinities on D₁, D₂ dopaminergic and α₁-, α₂ adrenergic receptors. The 3-(2-(4-(naphthalen-1-yl)piperazin-1-yl)ethyl)benzo[d][1,2,3]triazin-4(3H)- one 5 with K_i = 0.000178 nM was the most active and selective derivative for the 5-HT_1A receptor with respect to other serotonin receptors and the most selective derivative compared to dopaminergic and adrenergic receptors.