title: New antihistaminic theophylline or theobromine derivatives.
abstract: 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 micrograms/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 [RS-49014, 3,4-dihydro-1,3-dimethyl-7-[3-[4-[3-(phenylthio)propyl]piperazin-1 -yl]- 2-hydroxypropyl]-1H-purine-2,6-dione] was selected for clinical trials on the basis of a comparative pharmacological study with chlorpheniramine, ketotifen, promethazine, and theophylline.
authors.forename: J C
authors.initials: JC
authors.lastname: Pascal
authors.forename: S
authors.initials: S
authors.lastname: Beranger
authors.forename: H
authors.initials: H
authors.lastname: Pinhas
authors.forename: A
authors.initials: A
authors.lastname: Poizot
authors.forename: J P
authors.initials: JP
authors.lastname: Désiles
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001986:Bronchial Spasm / Q000276:immunology / Q000517:prevention & control; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists; D012882:Skin Tests; D013329:Structure-Activity Relationship; D013805:Theobromine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D012702:Serotonin Antagonists; D006632:Histamine; D013806:Theophylline; D000109:Acetylcholine; D013805:Theobromine