The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
In the course of testing a wide variety of compounds for possible use in mental disease it was found that 4-allyloxy-3,5-dipropylbenzoic acid (I; R = allyl) and a number of its derivatives greatly increased the sleeping time of mice given small doses of hexobarbital. These compounds also had a depressant effect on the motor activity of mice. Consequently a considerable number of derivatives and analogues were prepared. Those in which other ether substituents replace the allyloxy group, and esters, amide or nitrile functions replace the carboxyl group are included in this paper. These compounds are listed in Table I together with a few compounds (obtained from the same intermediates) in which one or both propyl groups are replaced by allyl groups (footnotes d and e). Table I gives the toxicities of these compounds and their pharmacological activities in the two tests mentioned above. More detailed discussion on the pharmacology is given below.Ethyl 3,5-diallyl-4-hydroxybenzoate (II) was obtained by repeated allylation and rearrangement from ethyl 4-hydroxybenzoate, as described by Claisen and Eisleb.1 This was hydrogenated to the 3,5-dipropyl ester (III) which was the starting material for most of these compounds as shown on the next page.When R = allyl, a satisfactory yield of the allyloxy ester (IV) could be obtained by refluxing a mixture of the phenolic ester and allyl bromide in acetone in the presence of solid potassium carbonate. Allyl chloride was not satisfactory. With some less * Presented in part before the Division of Medicinal Chemistry, American
In the preceding articles,1,2 it was reported that a considerable number of 4-allyloxy-3,5-dialkylbenzoic acids, esters, amides and nitriles (I; R = propyl, isopropyl, ethyl and methyl) greatly increase the sleeping time of mice given small doses of hexobarbital. We have now extended the series by replacing the alkyl groups with halogens (I; R = chlorine or iodine) and by the introduction of a methyl group into the 2-position (II).(II) Furthermore, we have prepared a series of analogues in which the allyloxy group is in the 2-position instead of the 4-positionAlthough many of these compounds were highly active, they were in general less active than the corresponding derivatives described in the preceding articles.1,2 * Presented in part before the Division of Medicinal Chemistry, American
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.