1-Acyl-, 3-acyl- and 1,3-diacyl-3-furfuryl-1-phenylthioureas with platelet antiaggregating and other activities.
The synthesis in excellent yields of 1-acyl-3-furfuryl-1-phenylthioureas 2 by reacting at t less than or equal to 10 degrees C 3-furfuryl-1-phenylthiourea 1, prepared in situ from furfurylamine and phenyl isothiocyanate, with aromatic or heterocyclic acyl chlorides in pyridine solution is described. 1-Acylthioureas 2 rearranged in high yields to 3-acylthioureas 3 by treatment with sodium hydroxide in heterogeneous phase. 1,3-Diacyl-3-furfuryl-1-phenylthioureas 4 were obtained in satisfactory yields by treatment of 1 with two moles of acyl chloride as in the case of 1-monoacylation. The thiourea 1 prepared in situ reacted with iodomethane in dimethylformamide solution and in the presence of sodium hydride to give in high yield the S-methyl derivative, namely the methyl ester of N-phenyl-1-furfurylaminethiocarboximidic acid. Some acylthioureas 2 and 4 showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid. The 1,3-diacylthiourea 4 c exhibited an appreciable anticonvulsant activity in mice and some compounds 2 and 4 moderate competitive antiacetylcholine and H1-antihistamine effects in vitro.
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
A
A
Ranise
F
F
Bondavalli
O
O
Bruno
S
S
Schenone
D
D
Donnoli
C
C
Parrillo
M L
ML
Cenicola
F
F
Rossi
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D007004:Hypoglycemic Agents; D010975:Platelet Aggregation Inhibitors; D010670:Phenylthiourea; D005662:Furaldehyde; D000109:Acetylcholine; D001241:Aspirin