Synthesis, toxicological and pharmacological assessment of 7-substituted derivatives of 1,3-dimethylxanthine

Article abstract of DOI:10.1016/0223-5234(94)90099-X

The synthesis of two 7-substituted theophylline derivatives from the theophylline sodium salt, dichloroalkane and N-methyl-N-cyclohexylamine is reported. The structures of the synthesized compounds were proved by microanalyses and ¹H-NMR data. Acute toxicity studies of the compounds were performed on mice and rats. A comparative pharmacological study of the in vivo broncholytic effect of the derivatives and aminophylline showed that the new compounds have different bronchodilatory activity and the compound 7-[2-(N-methyl-N-cyclohexyl)-aminoethyl]-1,3-dimethylxanthine tartrate 3a was more active than 7-[3-(N-methyl-N-cyclohexyl)-aminopropyl]-1,3-dimethylxanthine hydrochloride 3b. It was demonstrated that compound 3b and aminophylline exerted the strongest inhibitory effect on the enzyme activity of phosphodiesterase in lung homogenate. Compound 3a showed a slight inhibitory effect on the enzyme activity in this homogenate. The possible mechanisms of the broncholytic effects of these compounds are discussed.