| Literature DB >> 29534798 |
Shawn J Stachel1, Melissa S Egbertson2, Jenny Wai2, Michelle Machacek2, Dawn M Toolan3, John Swestock2, Donnie M Eddins4, Vanita Puri4, Georgia McGaughey5, Hua-Poo Su5, Debbie Perlow2, Deping Wang5, Lei Ma3, Gopal Parthasarathy5, John C Reid5, Pravien D Abeywickrema5, Sean M Smith3, Jason M Uslaner3.
Abstract
An internal HTS effort identified a novel PDE2 inhibitor series that was subsequently optimized for improved PDE2 activity and off-target selectivity. The optimized lead, compound 4, improved cognitive performance in a rodent novel object recognition task as well as a non-human primate object retrieval task. In addition, co-crystallization studies of close analog of 4 in the PDE2 active site revealed unique binding interactions influencing the high PDE isoform selectivity.Entities:
Keywords: Cognition; Optimization; PDE2; Phosphodiesterase inhibitor; Schizophrenia
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Year: 2018 PMID： 29534798 DOI： 10.1016/j.bmcl.2018.01.039
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823