Synthesis and biological activity of a novel class nicotinic acetylcholine receptors (nAChRs) ligands structurally related to anatoxin-a.

The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with α1, α7 and α3ß4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity.

8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors--part II.

8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT(1A/B/D) receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.

Phenylethynyl-pyrrolo[1,2-a]pyrazine: a new potent and selective tool in the mGluR5 antagonists arena.

The synthesis and the structure activity of a new series of pyrrolo[1,2-a]pyrazine is reported. These molecules are potent and selective non-competitive mGluR5 antagonists and may shed new light on the pattern of substitution tolerated by this receptor.

Synthesis and SAR of substituted tetrahydrocarbazole derivatives as new NPY-1 antagonists.

The SAR of a new series of tetrahydrocarbazole derivatives is described: the appropriate decoration of this template led to the identification of a new class of NPY-1 antagonists showing good in vitro potency and a promising in vivo pharmacokinetic profile in rat.