Synthesis of new piperazine-pyridazinone derivatives and their binding affinity toward α1-, α2-adrenergic and 5-HT1A serotoninergic receptors

We report the design and synthesis of a new class of piperazine-pyridazinone analogues. The arylpiperazine moiety, the length of the spacer, and the terminal molecular fragment were varied to evaluate their influence in determining the affinity of the new compounds toward the alpha(1)-adrenergic receptor (alpha(1)-AR), alpha(2)-adrenergic receptor (alpha(2)-AR), and the 5-HT1A serotoninergic receptor (5-HT1AR). Biological data showed that most of the compounds have an alpha(1)-AR affinity in the nanomolar or subnanomolar range, while affinity toward the other two receptors was lower in most cases. However, several of the tested compounds also showed very good (in the nanomolar range) or moderate affinity toward the 5-HT1AR subtype. (c) 2005 Elsevier Ltd. All rights reserved.