Design and synthesis of bridged piperidine and piperazine isosteres

Bioorg Med Chem Lett. 2018 Aug 15;28(15):2627-2630. doi: 10.1016/j.bmcl.2018.06.038. Epub 2018 Jun 19.

Abstract

We have developed versatile methods toward the synthesis of a variety of piperidine/piperazine bridged isosteres of pridopidine. The compounds were assessed against the D2 receptor in agonist and antagonist modes and against the D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied.

Keywords: C-arylation; Constrained amines; Dopaminergic activity; Oxabicyclic piperazines; Oxabicyclic piperidines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / pharmacology
  • Crystallography, X-Ray
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / pharmacology
  • Drug Design*
  • ERG1 Potassium Channel / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Piperazine / chemical synthesis
  • Piperazine / chemistry*
  • Piperazine / pharmacology
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D4 / agonists
  • Receptors, Dopamine D4 / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds
  • DRD2 protein, human
  • DRD4 protein, human
  • Dopamine Antagonists
  • ERG1 Potassium Channel
  • KCNH2 protein, human
  • Piperidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Piperazine
  • piperidine