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Publication Abstract from PubMed

To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition.

Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.,Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.