3,3-disubstituted 1-acyl-1-phenylthioureas with platelet antiaggregating and other activities.
This paper describes the synthesis in excellent yields of N-acyl-N-phenyl-1-pyrrolidine-, 1-piperidine-, 4-morpholine-, 1,2,3,4-tetrahydro-1-quinoline-, 1,2,3,4-tetrahydro-2-isoquinoline-, 10-phenothiazine- and 2,2'-dipyridylamine-carbothioamides by reaction of the corresponding 3,3-disubstituted 1-phenylthioureas, prepared in situ from the appropriate secondary amine and phenylisothiocyanate, with aromatic or heterocyclic acyl chlorides in pyridine solution or, in lower yields, in anhydrous dimethylformamide or pyridine solution in the presence of sodium hydride. N-phenyl-1-pyrrolidinecarbothioamide prepared in situ reacted with iodomethane in dimethylformamide solution and in the presence of sodium hydride to give excellent yield of the S-methyl derivative, namely the methyl ester of N-phenyl-1-pyrrolidinethiocarboximidic acid. Some of the above compounds, in particular the phenothiazine acylthioureas, showed platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some acylthioureas exhibited moderate hypoglycemic activity in rats and competitive antiacetylcholine and H1-antihistaminic effect in vitro inferior to that of atropine and chlorpheniramine, respectively.
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
A
A
Ranise
F
F
Bondavalli
O
O
Bruno
S
S
Schenone
C
C
Losasso
M
M
Costantino
M L
ML
Cenicola
D
D
Donnoli
E
E
Marmo
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000138:chemical synthesis / Q000494:pharmacology; D010640:Phenothiazines / Q000138:chemical synthesis / Q000494:pharmacology; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats
D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D007004:Hypoglycemic Agents; D007546:Isoquinolines; D009025:Morpholines; D010640:Phenothiazines; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D011759:Pyrrolidines; D011804:Quinolines; D015082:2,2'-Dipyridyl; D010670:Phenylthiourea; D000109:Acetylcholine