N-Acylhydrazones as inhibitors of PDE10A

Cyclic nucleotide phosphodiesterases (PDEs) are represented by a large superfamily of enzymes. A series of hydrazone-based inhibitors was synthesized and shown to be novel, potent, and selective against PDE10A. Optimized compounds of this class were efficacious in animal models of schizophrenia and may be useful for the treatment of this disease.

Graphical abstractA series of hydrazone-based compounds was synthesized and shown to be novel, potent, and selective inhibitors against phosphodiesterase 10A (PDE10A). Compound 56 which was shown to have a statistically significant effect in two different behavioral models of schizophrenia.Figure optionsDownload full-size imageDownload as PowerPoint slide