| Structural highlights
Function
[PDE9A_HUMAN] Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.[1]
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.
References
- ↑ Liu S, Mansour MN, Dillman KS, Perez JR, Danley DE, Aeed PA, Simons SP, Lemotte PK, Menniti FS. Structural basis for the catalytic mechanism of human phosphodiesterase 9. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13309-14. Epub 2008 Aug 29. PMID:18757755
- ↑ 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. Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia. J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01041
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