Synthesis and neuropharmacology of cyclobutanecarbonylureas

Ten urea derivatives of cyclobutanecarboxylic acid were synthesized and examined for general CNS depressant properties, barbiturate potentiation, myorelaxant, antitremorine and anticonvulsant potencies. Water solubility seems to play an important part in the activity of these compounds. However, lipid solubility also plays a part as activity determinant. 1-Cyclo-butanecarbonyl-3-ethylthiourea appears to be the most active CNS depressant, whereas the parent compound, cyclobutanecarbonylurea, is the most active barbiturate potentiator. Cyclobutanecarbonylurea, 1-cyclobutanecarbonyl-3-n-butylurea and 1-cyclobutanecarbonyl-3-(2,4-xylyl)urea appear to be the most active myorelaxants, while 1-cyclobutanecarbonyl-3-n-butylurea and 1-cyclobutanecarbonyl-3-(1-adamantyl)urea are the most active against pentylenetetrazole-induced convulsions. Cyclobutanecarbonylurea, 1-cyclobutane-carbonyl-3-n-butylurea, 1-cyclobutancarbonyl-3-cyanoacetylurea, 1-cyclobuta-necarbonyl-3-(1-adamantyl)urea and 1-cyclobutanecarbonyl-3-(2,4-xylyl)urea are also slightly active oxotremorine antagonists. None of the compounds possess significant analgesic activity.