Sintesi e studiSARdi nuove piattaforme tricicliche a struttura pirazolo-isochinolinica e pirazolo-naftiridinica come inibitori dell’enzima fosfodiesterasi 10A (PDE10A)

A new class of pyrazolo[5,1-a]isoquinolines, pyrazolo[5,1-f][1,6]naphthyridines, pyrazolo[5,1-a][2,6]naphthyridines, pyrazolo[5,1-a][2,7]naphthyridines and pyrazolo[1,5-h][1,7]naphthyridines were designed as bioisosteres of pyrazolo[1,5-c]quinazolines, described as potent inhibitors of PDE10A enzyme. In fact, bioisosteric modifications of the tricyclic core of the above known molecules might offer new templates that could provide optimized interactions with the PDE10A enzyme and desiderable pharmacokinetic properties. This work allowed to synthesize a small library of compounds incorporating a bi-substituted tricyclic pyrazole-based platform. A reproducible and efficientone-potsynthesis was achieved for the above-mentioned compounds.