Structure-based discovery and bio-evaluation of a cyclopenta[4,5]thieno[2,3-<i>d</i>]pyrimidin-4-one as a phosphodiesterase 10A inhibitor
Mayasah Al‐Nema, Anand Gaurav, Vannajan Sanghiran Lee, Baskaran Gunasekaran, Ming Tatt Lee, Patrick Nwabueze Okechukwu, Piyarat Nimmanpipug
Abstract
]pyrimidin-4-one scaffold from the zinc database exhibited a significant inhibitory activity of 1.60 μM against PDE10A. The modelling studies demonstrated that Zinc42657360 is involved in three hydrogen bonds with ASN226, THR187 and ASP228, and two aromatic interactions with TYR78 and PHE283, besides the common interactions with the P-clamp residues PHE283 and ILE246. The novel scaffold of Zinc42657360 can be used for the rational design of PDE10A inhibitors with improved affinity.
Topics & Concepts
PharmacophorePhosphodiesteraseVirtual screeningChemistryComputational biologyRational designDrug discoveryDocking (animal)Combinatorial chemistryPDE10AScaffoldPharmacologyStereochemistryBiochemistryEnzymeBiologyComputer scienceNanotechnologyMedicineDatabaseMaterials scienceNursingPhosphodiesterase function and regulationCholinesterase and Neurodegenerative DiseasesChemical synthesis and alkaloids