Synthesis, toxicological, pharmacological, and bronchodilating activity in vitro of some xanthineacetic acid derivatives.
The possibility of the preparation of some ester derivatives of dimethylxanthines from 1-theobromine- and 7-theophylline acetic acids and 7-(2-hydroxyethyl)-theophylline by DCC/DMAP-mediated esterification under mild conditions was studied. The structures of the compounds synthesized and by products isolated were demonstrated by microanalyses, UV-, IR-, and 1H NMR data. Acute toxicity assessment of the compounds on mice showed that compounds 4, 5, 6, and 7 are less toxic than aminophylline. A pharmacological study of the in vitro broncholytic effect (IC50 and pD2 values) of the derivatives and aminophylline showed that the new compound 4 (1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid 2-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purin-7-yl)ethyl ester) has a strong bronchodilating effect on serotonine- and acetylcholine-induced spasm in guinea pig trachea. The same compound does not influence barbiturate-induced hypnosis and locomotor activity, unlike to the effect of the aminophylline, used as a reference substance.
D000628:Aminophylline / Q000494:pharmacology* / Q000633:toxicity*; D000818:Animals; D001993:Bronchodilator Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors; D014132:Trachea / Q000187:drug effects*; D019820:Xanthine; D014970:Xanthines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity*
D001993:Bronchodilator Agents; D014970:Xanthines; D019820:Xanthine; D000628:Aminophylline