3-(4-Methylpiperazino)dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine and its 6-chloro and 12-chloro derivatives; Synthesis and pharmacology

Abstract

Dibenzo[b,f]-1,4-thiazepin-11(10H)-ones IIa-IIc reacted with phosphorus pentasulfide in pyridine under the formation of the thiones IIIa-IIIc which were transformed by treatment with hydrazine hydrate in 1-butanol to the hydrazine derivatives IVa-IVc. Reactions with triethyl orthoformate in ethanol in the presence of sulfuric acid effected cyclization to dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine (Va) and its chloro derivatives Vb, Vc which were treated with bromine in a boiling mixture of chlorofom and pyridine and gave the 3-bromo derivatives VIa-VIc. The title compounds Ia-Ic were obtained by substitution reactions with an excess of boiling 1-methylpiperazine. An attempt at preparing an analogous 14H-dibenzo[b,g]-1,2,4-triazolo[4,3-d]-1,4-thiazocine derivative was discontinued in the stage of reaction of the thione X with hydrazine hydrate which resulted in the azine XI. Compounds Ia-Ic on intravenous administration are highly toxic and inactive in tests for CNS effects; compound Ic showed a clear anticholinergic activity.

Novel Tricyclic-α-alkyloxyphenylpropionic Acids: Dual PPARα/γ Agonists with Hypolipidemic and Antidiabetic Activity

“…The residue was dissolved in ethanol (60 mL), hydrazine hydrate (1.3 mL) was added, the mixture was refluxed for 2 h and filtered, and the solvent was evaporated to give 2.4 g (96%) of ethyl 3-(4-(2-aminoethoxy)phenyl)-2-ethoxypropionate as an oil. A mixture of dibenzo[ b,f ]-1,4-thiazepin-11(10 H )-thione (2.20 g, 9 mmol), ethyl 3-(4-(2-aminoethoxy)phenyl)-2-ethoxypropionate (2.60 g, 8.9 mmol), and 3-methyl-1-butanol (70 mL) was stirred and heated at 150 °C for 16 h. The solvent was evaporated in vacuo, dichloromethane (50 mL) and water (50 mL) were added, the mixture was filtered, and the phases were separated. The organic phase was dried (MgSO 4 ), and the solvent was evaporated in vacuo to give a residue, which was purified by column chromatography on silica gel, eluting with chloroform.…”

The First Example of a Diastereoselective Thio-Ugi Reaction: A New Synthetic Approach to Chiral Imidazole Derivatives

“…Attention, heating isocyanide 1 at a temperature higher than 60 ° C can provoke an explosion . Spectroscopic data correlated with literature data …”

“…Thioamides are valuable precursors for many synthetic purposes. It is known that thioamides react with ammonia, amines, hydroxylamine, acetamide, hydrazine, and other nucleophiles. Recently, Kazmaier developed an effective method for synthesis of the thiazole derivatives.…”

Fused bicyclic 1,2,4‐triazoles with one extra sulfur atom: Synthesis, properties, and biological activity

“…Triazoothiazepines were first mentioned in 1983 by Polivka et al, [95] and all the known investigations dedicated to these systems are described below. .…”

“…. [95] The reaction of 4,6-dichloro-2-methylthiopyrimidine-5-carbaldehyde with 3-substituted 4-amino-1,2,4-triazole-5thiones at 50 C to 60 C in DMF gave 7-chloro-9-methylpyrimido [5,4- . [96] The reaction of 4-anilino-5-phenyl-4H-1,2,4-triazole-3-thiol with β-ketoesters yielded triazolothiazepines 47.…”