Biochemorphology of cyclobutanecarbonylureas

Ten urea derivatives of cyclobutanecarboxylic acid were synthesized and examined for general CNS depressant properties, barbiturate potentiation, and myorelaxant, antitremorine, and anticonvulsant potencies. Although water solubility plays an important role in the activity of these compounds, other factors also appear to be involved. 1-Cyclobutanecarbonyl-3,3-dimethylurea appears to be the most active CNS depressant, whereas 1-cyclobutanecarbonyl-3-(alpha-naphthyl)thiourea is the most active barbiturate potentiator. 1-Cyclobutanecarbonyl-3,3-dimethylurea, 1-cyclobutanecarbonyl-3-phenylurea, and 1-cyclobutanecarbonyl-3-tert-butylurea, 1-cyclobutanecarbonyl-3-allylurea, and 1-cyclobutanecarbonyl-3-phenylurea apparently are the most active against pentylenetetrazol-induced convulsions. 1-Cyclobutanecarbonyl-3-tert-butylurea, 1-cyclobutanecarbonyl-3,3-dimethylurea, and 1-cyclobutanecarbonyl-3-phenylurea are also slightly active tremorine antagonists.