Thiadiazine Derivatives as Antiprotozoal New Drugs

Abstract

The 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione scaffold have found many applications in recent years. This review is aimed at highlighting the most important aspects about these compounds: synthesis, spectroscopic characterization and antiprotozoan activities. How the chemical nature of N-substituents influences the overall activity / cytotoxicity profile will also be discussed.

Synthesis of 4-(1,3,5-Thiadiazinan-2-ylidene)-2-(3,4- dihydro-2H-1,3,5-thiadiazin-6-yl)pent-2-enedinitriles

“…1,3,5-Thiadiazines belong to an important class of heterocyclic compounds. The synthesis of 1,3,5-thiadiazines is successfully realized on the basis of Mannich-type aminomethylation [10][11][12][13]. 1,3,5-Thiadiazines are also of interest due a wide range of biological activity and practically important properties [12,14,15];…”

Thiadiazines, N,N-Heterocycles of Biological Relevance

“…In recent decades, the main studies on THTT derivatives have taken into account the molecular structure of these molecules to obtain an improved activity/cytotoxicity relationship [ 8 ]. In this context, we found many reports of the synthesis of several compounds with one THTT ring as the central core, with a great variety of substituents on the N-3 and N-5 position (mono-THTT) [ 8 , 9 , 10 , 13 , 19 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

“…The antiprotozoal [ 8 ], antibacterial [ 9 ], antifungal [ 10 ], anthelmintic [ 11 ] and tuberculostatic properties [ 12 , 13 ] of tetrahydro-2 H -1,3,5-thiadiazine-2-thione (THTT) have been known for several decades. In addition to its renowned antimicrobial activity, this versatile heterocycle has found an increasing number of applications in the drug research arena as a biolabile prodrug [ 14 ] in the design of drug delivery systems (DDSs) due to its high lipid solubility and enzymatic rate of hydrolysis.…”

Synthesis of partially hydrogenated 1,3,5-thiadiazines by Mannich reaction

“…13 Carboxylic acids 4 have been identified as effective antiprotozoal agents, suitable for the treatment of trypanosomiasis, leishmaniasis and trichomoniasis; 14 the synthesis and biological activity of these compounds have been recently reviewed. 15 The most widely used compound of THTT series is 3,5-dimethyltetrahydro-1,3,5-thiadiazine-2-thione (5), known by the trade names Dazomet, Tiazone (in USSR), Basamid, Mylone, DMTT, and applied as highly potent soil fumigant, fungicide, herbicide, and powerful insecticide, as well as for the prevention of biofilm accumulation in paper industry. 16 Chemistry of Heterocyclic Compounds 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126]...…”

“…Thus, recent publications have reviewed the literature about synthesis 15,35 and biological activity of THTTs. 15,35,36 The chemistry of 1,3,5-thiadiazine has been featured in reviews, 37 devoted to the cyclothiomethylation reaction of primary amines. The synthesis and reactions of isomeric triazolo-1,3,5-thiadiazines was briefly considered in another review.…”