Synthesis and potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines

J Med Chem. 1988 Feb;31(2):454-61. doi: 10.1021/jm00397a032.

Abstract

The synthesis of a series of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines is reported along with the effects of these compounds in preclinical tests for antipsychotic activity. Certain of these compounds displayed antipsychotic-like effects in conditioned avoidance tests, but unlike currently used antipsychotic drugs, they did not have affinity for brain dopamine receptors. These compounds also did not cause dystonias predictive of extrapyramidal side effects in monkeys at doses that produced behavioral effects. On the basis of this unique biological profile, a member of this series 7,8-dihydro-8-ethyl-1,3,5-trimethyl-1H-imidao[1,2-c]pyrazol[3,4-e] pyrimidine (19, CI-943), has been selected for clinical evaluation as an antipsychotic agent.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / toxicity
  • Avoidance Learning / drug effects
  • Cebus
  • Imidazoles / chemical synthesis*
  • Mice
  • Motor Activity / drug effects
  • Pyrazoles / chemical synthesis*
  • Pyrimidines / chemical synthesis*
  • Rats
  • Receptors, Dopamine / drug effects
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Imidazoles
  • Pyrazoles
  • Pyrimidines
  • Receptors, Dopamine