Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia.

Abstract A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model.