Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor

Bioorg Med Chem. 1998 Oct;6(10):1731-43. doi: 10.1016/s0968-0896(98)00134-5.

Abstract

Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved.

Publication types

  • Comparative Study

MeSH terms

  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / metabolism*
  • Antipsychotic Agents / pharmacology
  • Drug Design
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / metabolism*
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Piperazines / chemical synthesis*
  • Piperazines / metabolism*
  • Piperazines / pharmacology
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Structure-Activity Relationship

Substances

  • 3-(4-(4-methoxyphenyl)piperazin-1-ylmethyl)-1,4-dihydro-5-oxa-1,2-diazacyclopenta(a)naphthalene
  • Antipsychotic Agents
  • DRD4 protein, human
  • Heterocyclic Compounds
  • Ion Channels
  • Piperazines
  • Pyrazoles
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4