(1,3-Dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones. A series of novel central nervous system depressants.
A series of novel (1,3-dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones was synthesized. Pharmacological evaluation of these compounds demonstrated central nervous system depressant activity, potential anticonvulsant properties, and a low order of acute toxicity. In addition, selected compounds showed potential antipsychotic effects. This report focuses on the synthesis and structure-activity relationships of these compounds. (5-Amino-1-ethyl-3-methyl-1H-pyrazol-4-yl)(2-chlorophenyl) methanone (21) was the most active compound against pentylenetetrazole-induced convulsions. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-chlorophenyl)methanone (4) also has a favorable anticonvulsant depression ratio. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-trifluoromethylphenyl)methan one (8), (5-amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-thienyl)methanone (13), and (5-amino-3-ethyl-1-methyl-1H-pyrazol-4-yl)phenylmethanone (14) are very potent depressants. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-thienyl)methanone (12) possessed marked central depressant activity without anticonvulsant activity and without impairment of motor functioning. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl) (2-fluorophenyl)methanone (2) has a behavioral profile suggestive of antipsychotic activity and gave a positive Ames test result.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D002492:Central Nervous System Depressants / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011187:Posture; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D007659:Ketones; D011720:Pyrazoles