New Antihistaminic Theophylline or Theobromine Derivatives

Article abstract of DOI:10.1021/jm50001a019

A series of 3,4-dihydro-1,3-dimethyl-7-<3-(4-substituted-piperazin-1-yl)-substituted-alkyl>-1H-purine-2,6-diones and 3,7-dihydro-3,7-dimethyl-1-<3-<4-substituted-piperazin-1-yl)-substituted-alkyl>-1H-purine-2,6-diones was synthesized and evaluated for antihistaminic activity.Some of them displayed good inhibition of both histamine-induced bronchospasm in the anesthetized guinea pig at 10 μ/kg by the intravenous route and of passive cutaneous anaphylaxis in the rat at 10 mg/kg by the oral route.Comparison of the two most active compounds revealed a higher antihistaminic activity with the compounds containing a (phenylthio)propyl group (1 and 2) as compared with that containing a phenoxy group.Compound 2 piperazin-1-yl>-2-hydroxypropyl>-1H-purine-2,6-dione> was selected for clinical trials on the basis of a comparative pharmacological study with chloropheniramine, ketotifen, promethazine, and theophylline.