Studies on Nitrogen-free Hypnotics. II

Syntheses and Hypnotic Actions of Alkylcoumarin Derivatives

Abstract

Nine kinds of alkylcoumarin derivatives were prepared and their hypnotic effect and toxicity were compared with those of 4-methylcoumarin as the standard. It was thereby found that the alkyl group (methyl to butyl) in the 3-position of the coumarin ring effected hypnotic action when the number of carbon atoms in the alkyl was odd and toxic action when such number was even, with the peak toxicity with the ethyl group. The effect of the methyl group into the coumarin ring was found to be in the decreasing order of 8-, 3-, and 4-methyl, while that of the toxicity was in the increasing order of 4-, 8-, 3-, 5-, 7-, and 6-methyl compounds. Side effects, such as convulsion, was not observed in 3-propyl-, 4-methyl-, and 8-methylcoumarins, while sedative action was observed in 3-methyl, 4-methyl-, 5-methyl-, 8-methyl-, 3-propyl-, and 3-butylcoumarins. In general, the difference between HD₅₀ and LD₅₀ seemed to be slight in alkyl coumarins, with the exception of 4-methyl- and 8-methylcoumarins.