クマリン誘導体の薬品的研究 (第5報)

鎭静・催眠作用に就いて その2

抄録

Sedative and hypnotic actions, and toxicity against mice were tested with 20 kinds of coumarin derivatives synthesized and three kinds of market products. Efficacy and toxicity of each preparation were compared by the values of lethal dose, LD₆₀, hypnotic dose, HD₆₀, and sedative dose, SD₆₀, calculated by the Van der Waerden's Flächenmethode and by the Behrens-Kärber method (cf. Tables and Figs.). Results obtained can be summarized as follows:
1) Efficacy is lost when -CH₂- is introduced between the coumarin ring and CO-N(C₂H₅)₂ of coumarin-3-carboxylic acid diethylamide to coumarin-3-acetic acid diethylamide.
2) Exchange of -CO- in coumarin-3-carboxylic acid diethylamide with -O- to isocou-marincarboxylic acid diethylamide did not affect the efficacy to any great extent, but its methyl ester lacked any efficacy.
3) Introduction of -COOH, -COOCH₃, or -COOCH₂H₅, in the 5-position of α-pyrone ring, in place of the benzene ring, in coumarin nucleus, did not add any efficacy.
4) In any case, free carboxylic acid possessed no efficacy.
5) Coumarin itself did not possess any efficacy but 2-thiocoumarin was effective.
6) Hydrogenation of the double bond between 3- and 4-positions decreased the efficacy, with the exception of coumarin-3-acetic acid diethylamide.
7) Efficacy was not shown by the introduction of -NO₂ and -NH₂ in the 6-position, of isoamyl in the 6-position, and -OH in the 7-position or of -COCH₃ in the 3-position of the coumarin ring.
8) The sodium salt of barbital used as the control was more weaker in both efficacy and toxicity than the free base.