3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants

J Med Chem. 1985 Feb;28(2):256-60. doi: 10.1021/jm00380a020.

Abstract

A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. Compounds were synthesized by Michael addition of acrylonitrile to diphenylpyrazole followed by reductive alkylation of the resultant diphenylpyrazolepropionitriles. Compound 3 was equipotent with imipramine in standard antidepressant assays in animals but showed no significant anticholinergic action and did not antagonize the antihypertensive effects of clonidine and guanethidine.

MeSH terms

  • Animals
  • Antidepressive Agents / chemical synthesis*
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Imipramine / pharmacology
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Motor Activity / drug effects
  • Norepinephrine / metabolism
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Serotonin / metabolism

Substances

  • Antidepressive Agents
  • Pyrazoles
  • Serotonin
  • 3,4-diphenyl-1H-pyrazole-1-propanamine
  • Imipramine
  • Norepinephrine