Abstract In order to improve the chemotherapeutic value of bis (4‐aminophenyl)‐sulfone, an agent active against tuberculosis, leprosy, and a number of bacterial infections but too toxic for clinical use, it was condensed with vitamin C (1‐ascorbic acid) in methanol solution to form a crystalline product. This new derivative has a LD 50 of 987.7 ± 94.8 mg per kilo (mice, oral). Compared with the LD 50 of bis (4‐aminophenyl)‐sulfone, which is 12.6 mg/kilo (mice, oral), the vitamin C derivative is only one eightieth as toxic. In a concentration of 0.2 mg per 10 cm 3 culture, it inhibited completely the growth of T. B. from 96 to 168 hours; in a concentration of 0.02 mg per 10 cm 3 culture, it was found to be still bacteriostatic. The vitamin C derivatives of sulfa drugs were also prepared and studied. The antitubercular activity of the vitamin C derivatives of sulfathiazole, sulfadiazine and sulfamerazine was found to be of the same magnitude as salicylacetone, which inhibited completely the growth of T.B. in a concentration of 2 mg per 10 cm 3 culture.
(1) Substitution of dithiocarboxymethyl or dithiocarboxyphenyl groups (in p-carbamidophenylarsenous acid) did not appreciably alter amebacidal activity, in vitro or in vivo. (2) Toxicity and tolerance tests in mice, rats, rabbits and monkeys indicated that the dithiocarboxyphenyl derivative was the least toxic. (3) Reaction of the gastric mucosa and peritoneum to the direct application of dithio derivatives was less severe than to the arsenoxide. The liver, lungs and kidneys were appreciably damaged after single toxic doses of the arsenoxide. (4) Within the range of therapeutic activity, the short-term (11 day) chronic toxicity test in rats and the 30-day chronic tolerance test in monkeys resulted in minimal damage to tissues after the dithio derivatives. (5) After carbarsone oxide (p-carbamidophenyl arsenous oxide), distribution studies revealed exceptionally high levels of arsenic in the bile, blood and urine, moderate amounts in the feces, and contents of the stomach and small intestine, and in the colon, kidneys and liver, and smaller amounts in the lungs, heart and spleen. Appreciable tissue levels persisted for at least 9 days in rats after chronic intragastric therapy. (6) Dithio derivatives (C.C. 914 and 1037) also accumulated in large amounts in bile, feces, urine, liver, kidneys, cecum and colon, with moderate amounts in contents of the stomach, cecum, and small intestine, blood, lungs, heart and spleen, and small amounts in brain, pleural and peritoneal fluids and thymus. The levels attained in these tissues in rats and rabbits after short-term chronic toxicity tests, were appreciably higher than in monkeys, on the 30-day chronic tolerance test. (7) As with other arsenoxides, the arsenic of carbarsone oxide and its dithio derivatives, was bound by tissues roughly in proportion to the toxicity of each drug. Higher concentrations in intestinal tissue and in bile have been reported following injection of phenyl arsenoxides than after proportional doses of arsonic acids (10). This observation was confirmed and is believed to be significant. (8) The suggestion of Voegtlin (2) that protozoa contain and are dependent upon smaller absolute amounts of -SH groups than mammalian tissue cells agrees with the experimental evidence presented.
Abstract Fifty crystalline p ‐nitrophenyl‐ureas have been prepared by the condensation of either p ‐nitrobenzazide or its pyrolysis product, p ‐nitrophenyl isocyanate, with various types of amines in boiling toluene solution. The yields were in general very high and the derivatives were suitable for the purpose of identification.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 4,4'-Diamidinostilbene HydrochloridePeter P. T. SahCite this: J. Am. Chem. Soc. 1942, 64, 6, 1487–1488Publication Date (Print):June 1, 1942Publication History Published online1 May 2002Published inissue 1 June 1942https://pubs.acs.org/doi/10.1021/ja01258a508https://doi.org/10.1021/ja01258a508research-articleACS PublicationsRequest reuse permissionsArticle Views115Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Abstract A general method for the synthesis of 2‐alkyl‐1,4‐naphthoquinones and hydroquinones from 1,4‐naphthoquinone as the starting material is described in this paper, with special references to 2‐methyl‐1,4‐naphthoquinone, 2‐methyl‐1,4‐naphtho‐hydroquinone, the dimethyl ether, the diacetate, the dipropionate, and the dibenzoate of the synthetic 2‐methyl‐1,4‐naphtho‐hydroquinone, which have recently been shown to possess strong anti‐hemorrhagic vitamin K activity.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)