{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(7)"],"submitter":["Wu XN"],"pubmed_abstract":["Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe <b>3a</b>. However, compound <b>3a</b> is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead <b>15</b> exhibited potent inhibitory activity against PDE8A (IC<sub>50</sub> = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of <b>15</b> significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse m"],"journal":["Acta pharmaceutica Sinica. B"],"pagination":["3103-3112"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9293670"],"repository":["biostudies-literature"],"pubmed_title":["Structure-based discovery of orally efficient inhibitors <i>via</i> unique interactions with H-pocket of PDE8 for the treatment of vascular dementia."],"pmcid":["PMC9293670"],"pubmed_authors":["Luo HB","Li Z","Zhou Q","Xie X","Wu XN","Wu Y","Huang YD"],"additional_accession":[]},"is_claimable":false,"name":"Structure-based discovery of orally efficient inhibitors <i>via</i> unique interactions with H-pocket of PDE8 for the treatment of vascular dementia.","description":"Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe <b>3a</b>. However, compound <b>3a</b> is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead <b>15</b> exhibited potent inhibitory activity against PDE8A (IC<sub>50</sub> = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of <b>15</b> significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse m","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-19T09:24:12.925Z","creation":"2022-08-08T09:51:19.563Z"},"accession":"S-EPMC9293670","cross_references":{"pubmed":["35865094"],"doi":["10.1016/j.apsb.2022.02.012"]}}