Derivatives of Acetamide and Benzamide as Hypnotics

Abstract

IT has been known since 19101 that certain dialkyl-arylacetamides possess sedative, hypnotic and antipyretic properties, and Lumibre and Perrin2 later described the hypnotic activity of phenylacetamides in dogs. Trialkylacetamides have been reported to possess spasmolytic3 and hypnotic4 properties, but none of the compounds described appears to have found its way into clinical use.Our interest in 3-methylpentynol, and in hypnotics in general, led us to reinvestigate and extend earlier work in this connection, in the hope of discovering a compound with hypnotic properties intermediate between those of methylpentynol and the barbiturates, but without the disadvantages of the latter.Although a number of active compounds were found, none was sufficiently outstanding to justify its introduction to clinical use. Nevertheless, in addition to the preparation of a number of new compounds, we have attempted a correlation of their hypnotic activity and chemical constitution within the group of acetamide derivatives.Benzamide5 has also been reported to possess hypnotic properties and a number of derivatives have been examined, but without discovering any which was of practical interest. NARCOTIC EFFECTThe criterion of narcotic activity adopted was the abolition of the righting reflex in mice. Screening tests were carried out at four geometric dose levels, 1-14, 0.77, 0.52 and 0.35 g./kg. on groups of five female mice (Schofield strain), with methylpentynol as the reference compound in all cases, and observations were made at half an hour, 1 hour, and then hourly intervals up to 6 hours after oral administration of the appropriate dose in suspension in 5 per cent acacia solution. The doses chosen were such that on the top dose all the animals treated with methylpentynol invariably showed abolition of the righting reflex, whereas on the lowest dose only rarely did more than one animal show a positive response. Only in those in which the narcotic activity of the compound was similar or greater than that of methylpentynol, was a more detailed examination made using a larger number of animals, except when it appeared necessary to assist correlation of narcotic activity with

Remarkable Similarity of Molecular Packing in Crystals of Racemic and Enantiopure 2-Phenylpropionamide: Z′ = 4 Structures, Molecular Disorder, and the Formation of a Partial Solid Solution

“…Like 2phenylbutyramide, 2PPA exhibits pharmacological activity. 15 Here, we report the crystal structures of racemic and enantiopure forms of 2PPA and discuss the reasons why these structures are remarkably similar. Additionally, using anomalous dispersion of X-rays, we confirmed the relation between the signs of optical rotation and the absolute configurations of 2PPA enantiomers.…”

“…This simplicity makes it an interesting structural model for this class of compounds. Like 2-phenylbutyramide, 2PPA exhibits pharmacological activity …”