title: BN/CC isosterism in borazaronaphthalenes towards phosphodiesterase 10A (PDE10A) inhibitors.
abstract: The application of BN/CC isosterism is explored as a method of expanding the scope of core scaffolds in biologically active compounds. The viability of potential drug candidates incorporating BN-heteroaromatic moieties was investigated through the synthesis of BN-substituted analogs to known phosphodiesterase (PDE10A) inhibitors, namely MP10 and a selection of N-methylanilide analogs. These in some cases revealed unexpectedly potent and relatively stable derivatives, providing further support for the potential of BN-incorporation in medicinal chemistry.
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Vlasceanu
authors.affiliation: Discovery Chemistry and DMPK, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Jessing
authors.affiliation: Discovery Chemistry and DMPK, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark. Electronic address: JPK@lundbeck.com.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Kilburn
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D006801:Humans; D062105:Molecular Docking Simulation; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases
keywords: Antipsychotics; Borazaronaphthalenes; PDE10A inhibitors