title: Synthesis of 6-thiosubstituted 5-ethoxycarbonyl-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones, 6-substituted 5-hydroxy-1,3-diphenyl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their esters with local anesthetic, antiarrhythmic, antiinflammatory and analgesic activities.
abstract: The synthesis of 6-thiosubstituted 5-ethoxycarbonyl-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin- 4(1H)-ones 3, and of 6-substituted 5-hydroxy-1,3-diphenyl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones 5 and their esters 6 is described. These derivatives were prepared in order to evaluate the influence on the pharmacological profile of alkyl substituents bearing polar/hydrophilic functionalities at an enethiol substructure as in compounds 3 or to assess the effects arising from the incorporation of the sulfur atom in a thiophene moiety as in thienopyrimidinones 5 and 6 in comparison with a series of 5-substituted 6-acylthio-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 1c,d, previously described. Preliminary screenings suggest that all tested compounds maintained or even increased the local anesthetic activity, but failed in the platelet antiaggregating activity; on the other hand, antiarrhythmic and antiinflammatory activity was preserved in some esters 6.
authors.affiliation: Dipartimento di Scienze Farmaceutiche dell'Università, Genova.
authors.forename: A
authors.initials: A
authors.lastname: Ranise
authors.forename: O
authors.initials: O
authors.lastname: Bruno
authors.forename: S
authors.initials: S
authors.lastname: Schenone
authors.forename: F
authors.initials: F
authors.lastname: Bondavalli
authors.forename: G
authors.initials: G
authors.lastname: Falcone
authors.forename: W
authors.initials: W
authors.lastname: Filippelli
authors.forename: S
authors.initials: S
authors.lastname: Sorrentino
mesh_terms: D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D066298:In Vitro Techniques; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
chemical_list: D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011744:Pyrimidinones