Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine series of histamine H3 receptor antagonists

Bioorg Med Chem Lett. 2006 Feb 15;16(4):989-94. doi: 10.1016/j.bmcl.2005.10.087. Epub 2005 Nov 15.

Abstract

A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme Inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Guinea Pigs
  • Haplorhini
  • Histamine Antagonists / chemical synthesis
  • Histamine Antagonists / chemistry
  • Histamine Antagonists / pharmacology*
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Rats
  • Receptors, Histamine H3 / drug effects*
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Histamine Antagonists
  • Imidazoles
  • Piperidines
  • Receptors, Histamine H3