2-[4-(o-methoxyphenyl)piperazin-1-ylmethyl]-1,3-dioxoperhydroimidazo[1,5-a]pyridine as a new selective 5-HT1A receptor ligand

A series of 2-[ω-(4-arylpiperazin-1-yl)alkyl]-1,3-dioxoperhydroimidazo[1,5-a]pyridine derivatives was prepared and evaluated for affinity at 5-HT1A and α1 receptors. The most promising analogue 1m bound at 5-HT1A sites with nanomolar affinity (Ki=31.7) and high selectivity over α1, D2 and 5-HT2A receptors (Ki>1000, Ki>10 000, Ki>1000 nM, respectively). Preliminary studies showed that this agent is a presynaptic 5-HT1A agonist, and it displayed activity in the face to face behavioural model.