Coumarin Derivatives for Medicinal Purposes. XII

Hypothermal Action

Abstract

A total of 73 kinds of compounds, including 11 derivatives of alkylcoumarin, 2 of 2-thiocoumarin, 3 of oxocoumarin, 4 of 6-nitrocoumarin, 14 of aminocoumarin, 9 of hydroxycoumarin, 9 of carboxylic acid, 9 of naphthopyrone, and 12 of coumarin homologs were prepared and their structure-activity relationship was examined by screening the activity of body temperature depression with albino rats. In general, almost all coumarin derivatives showed the activity and coumarin itself had a comparatively strong effect. In methylcoumarin derivatives, the effect was generally stronger when the methyl group was in the α-pyrone ring than in the benzene ring. In 3-alkylcoumarin derivatives, methyl and propyl derivatives had strong activity, while ethyl and butyl derivatives had weaker action. Saturation of the double bond in 3-4 position in coumarin and 4-methylcoumarin with hydrogen decreased the effect, the change of the ketone group in 2-position to thione group failed to show any change in effect, and introduction of a nitro or amino group in 6-position decreased the effect, the amino group being affected less. However, its acetylated or benzoylated compounds had only a weak effect. In general, derivation of the amino group to its hydrochloride increased the effect. Introduction of a carboxyl in the 3-position increased toxicity, while this group in 4- or 6-position decreased both the toxicity and effect. Oxocoumarin, hydroxycoumarin, and naphthopyrone derivatives had only a weak effect. The change of α-pyrone to γ-pyrone ring to form chromone left majority of the effect intact but the effect was very weak in isocoumarincarboxylic acid derivatives, coumarinic acid, phthalide, coumarone, 2-acetylcoumarone, coumarane, coumalinic acid, chelidonic acid, and diethyl chelidonate.