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.