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

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):235-9. doi: 10.1016/j.bmcl.2011.11.023.
Shu-Wei Yang  1 ,  Jennifer Smotryski ,  William T McElroy ,  Zheng Tan ,  Ginny Ho ,  Deen Tulshian ,  William J Greenlee ,  Mario Guzzi ,  Xiaoping Zhang ,  Deborra Mullins ,  Li Xiao ,  Alan Hruza ,  Tze-Ming Chan ,  Diane Rindgen ,  Carina Bleickardt ,  Robert Hodgson
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. [email protected]
PMID: 22142545 DOI: 10.1016/j.bmcl.2011.11.023
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.

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