- Synthesis, toxicological, pharmacological, and bronchodilating activity in vitro of some xanthineacetic acid derivatives
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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.
- Peikov,Danchev,Zlatkov,Ivanov,Belcheva
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p. 615 - 618
(2007/10/03)
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