THE RELATIONSHIP BETWEEN CHEMICAL STRUCTURE AND CENTRAL DEPRESSANT ACTION OF SUBSTITUTED ETHERS OF GLYCEROL

¹ University of Rochester, School of Medicine and Dentistry, Rochester 7, New York

1) Many substances of the structure R-O-CH₂-CHOH-CH₂OH produced transient muscular relaxation and paralysis. These effects were due to a depressant action on the central nervous system and particularly on the spinal cord.

2) The paralyzing action was strongest when R was a benzene nucleus substituted in the ortho position with a small alkyl or alkoxy group or chlorine. Compounds with these radicals in meta or para positition were less active than the ortho isomers. The presence of a hydroxy, amino, amido, ester or hydroxy-alkyl group or multiple substitution in the ring with alkyls, halogens or both decreased paralyzing activity.

3) When R was an aliphatic radical, straight chain alkyls contributed more to the paralyzing activity than the branched chain isomers or unsaturated radicals. The n-amyl ether was the most potent compound of the aliphatic series.

4) Methyl substitution on the C₂ atom of the glyceryl side chain did not materially alter paralyzing activity but substitution on the C₁ atom decreased activity.

5) Substitution in the hydroxyl groups decreased or destroyed paralyzing activity.

6) Compounds possessing the structure R-S-CH₂-CHOH-CH₂OH or R-SO₂-CH₂-CHOH-CH₂OH also had paralyzing activity, but were more toxic than the oxygen ethers.

7) Compounds of the structure aryl-O-CH₂-CHOH-CH₂OH and aryl-S-CH₂-CHOH-CH₂OH increased the threshold to electrically induced convulsions. There was no simple relation between the anticonvulsant and paralyzing activity of the compounds and the anticonvulsant action could not be significantly altered by alkyl or alkoxy substitution in the nucleus.