3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants.
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.
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000928:Antidepressive Agents; D011720:Pyrazoles; D012701:Serotonin; C044513:3,4-diphenyl-1H-pyrazole-1-propanamine; D007099:Imipramine; D009638:Norepinephrine