5-Substituted 2,3-dihydro-6-mercapto-1,3-diphenyl-2-thioxo-4(3H)-pyrimidinones and their 6-(acylthio) derivatives with platelet antiaggregating, antiinflammatory, antiarrhythmic, antihyperlipidemic and other activities.
The synthesis in excellent yields of 2,3-dihydro-6-mercapto-1,3,5-triphenyl-2-thioxo-4(3H)-pyrimidinone 3 and 5-ethoxycarbonyl-2,3-dihydro-6-mercapto-1,3-diphenyl-2-thioxo-4(3H )- pyrimidinone 4 by reaction of methyl phenylacetate or diethyl malonate, respectively, with phenyl isothiocyanate (3 molar equivalents) and sodium hydride (2 molar equivalents) in DMF solution is described. Acylation of 3 and 4 with acyl chlorides gave, generally in satisfactory yields, 6-acylthio derivatives 13 and 14. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as remarkable antiinflammatory, antiarrhythmic, local anesthetic and antihyperlipidemic activities in rats and in mice. Weak anticonvulsant and hypoglycemic activities were also detected.
Ranise
A
A
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
Bruno
O
O
Bondavalli
F
F
Schenone
S
S
D'Amico
M
M
Falciani
M
M
Filippelli
W
W
Rossi
F
F
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; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010975:Platelet Aggregation Inhibitors; D011744:Pyrimidinones