BN/CC isosterism in borazaronaphthalenes towards phosphodiesterase 10A (PDE10A) inhibitors

Bioorg Med Chem. 2015 Aug 1;23(15):4453-4461. doi: 10.1016/j.bmc.2015.06.019. Epub 2015 Jun 15.

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.

Keywords: Antipsychotics; Borazaronaphthalenes; PDE10A inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / chemical synthesis
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / metabolism
  • Binding Sites
  • Catalytic Domain
  • Humans
  • Molecular Docking Simulation
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry*
  • Naphthalenes / metabolism
  • Phosphodiesterase Inhibitors / chemical synthesis
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / metabolism
  • Phosphoric Diester Hydrolases / chemistry*
  • Phosphoric Diester Hydrolases / metabolism
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Naphthalenes
  • Phosphodiesterase Inhibitors
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases