Design, synthesis and dopamine D4 receptor binding activities of new N-heteroaromatic 5/6-ring Mannich bases

Bioorg Med Chem. 2009 Jul 1;17(13):4448-58. doi: 10.1016/j.bmc.2009.05.015. Epub 2009 May 12.

Abstract

A series of phenylpiperazine-methyl-substituted 1H-pyrrolo[2,3-c]pyridine, imidazo[1,2-c]-, pyrrolo[2,3-d]- and pyrrolo[3,2-d]pyrimidines were prepared as selective dopamine D4-ligands. The pyrrolo[2,3-d]pyrimidine derivatives 12d (K(i)=1,9 nM) and 34 d (K(i)=2,4 nM) as well as the pyrrolo[3,2-d]pyrimidine Mannich base 49f (K(i)=2,8 nM) showed high dopamine D4 receptor activity superior to the atypical antipsychotic agent clozapine.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / pharmacology*
  • CHO Cells
  • Cattle
  • Clozapine / pharmacology
  • Cricetinae
  • Cricetulus
  • Humans
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Protein Binding
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D4 / metabolism*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Piperazines
  • Pyrimidines
  • Receptors, Dopamine
  • Receptors, Dopamine D4
  • Clozapine
  • phenylpiperazine