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The present minireview concerns the application of cyclic isothiourea moiety (with endocyclic sulfur atom) in drug design and includes the examples of bioisosteric replacement, conformational restriction, etc. The synthetic procedures leading to the target structures of cyclic isothioureas and their bicyclic derivatives are also discussed. The review gives multiple useful examples for the chemists searching novel heterocyclic compounds with neuroprotective, antihypotensive, antiproliferative, antiobestic, and analgetic properties.

We propose a new method for assembling the imidazo[2,1-b][1,3]thiazole system, based on the reaction of (2Z)-1,3-diaryl-4-bromobut-2-en-1-one derivatives with 2-aminothiazoles. The outcome of this reaction depends on the structure of the starting bromo ketone: when electron-withdrawing substituents are present in the structure of the ketone, a competing reaction occurs, which leads to the formation of 2,5-diarylfurans. Screening for antitumor activity has been performed in the case of 1-phenyl-2-(6-phenyl-5,6-dihydroimidazo[2,1-b]- thiazol-6-yl)ethanone and this compound has shown moderate ability to suppress the growth of kidney cancer cells, with a weaker effect on the cell lines of prostate cancer, colon cancer, and leukemia.

Thiazole has widespread importance in materials and medicines. Several reviews are reported which cover essential properties of thiazoles such as pharmacological activities, structure-activity relationship studies, and various synthetic routes. However, synthesis based on a greener approaches, particularly metal-free reactions, usage of mild, nontoxic, recyclable catalysts, eco-sustainable protocols, efficient solvents have not been exclusively reviewed. Current review emphasizes green synthetic approaches for substituted thiazoles that have been performed within the last decade.

The review is devoted to the methods of synthesis of furan, pyran, and thiazole derivatives employing aryltellurium trihalides published in 1983–2019.

The review summarizes the publications devoted to the synthesis of pyrrolo[2,1-b]thiazoles with a various degree of saturation and substitution over the last 10 years. The synthesis methods are conditionally divided into three groups depending on the starting compounds: modification of thiazole derivatives, modification of derivatives of other heterocycles, as well as synthesis from acyclic compounds.

A three-step method was designed and developed on the basis of retrosynthetic analysis for the synthesis of hybrid molecules containing a thiazole ring and an N-sulfonyl amidine fragment, connected by a methylene linker. The mechanism of the last step involves the formation of intermediate 1,2,3,4-thiatriazoles and their transformation into the final products as a result of the elimination of molecular nitrogen and sulfur.

A new series of 4,4'-(3,5-diphenethylbenzo[1,2-b:5,4-b']difuran-2,6-diyl)bis(N-(het)arylthiazol-2-amine) derivatives have been synthesized from 1,1'-(3,5-diphenethylbenzo[1,2-b:5,4-b']difuran-2,6-diyl)diethanone O,O'-diacetyl dioxime and substituted isothiocyanates under conventional and microwave irradiation conditions. The obtained products were subjected to in vitro antibacterial and antimycobacterial activity tests. Some of the compounds exhibited noteworthy antibacterial activity against Bacillus subtilis (+ve) and Pseudomonas aeruginosa (-ve) strains and antimycobacterial activity against Mycobacterium bovis strain.

2-Alkylidene-5-methylidene-1,3-thiazolidin-2-ylidenes react with N-bromosuccinimide to form 2-alkylidene-5-(bromomethyl)-2,3-dihydro-1,3-thiazoles, the reaction of which with S,O,N-nucleophiles is used for the selective synthesis of the corresponding 5-methylfunctionalized derivatives.

The reaction between dehydrobenzene and tetrahydropyrido[4,3-d]pyrimidin-4-ones condensed with isoxazole, thiazole, thiadiazole, or triazole rings resulted in Hofmann cleavage of the tetrahydropyridine moiety with the formation of 6-vinyl-substituted pyrimidones fused with the corresponding azole rings.

6-Arylidene-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5(6Н)-ones reacted with N-alkylazomethine ylides by [2+3] cycloaddition mechanism, resulting in the formation of diastereomeric spiro[imidazo[2,1-b][1,3]thiazole-6,3'-pyrrolidin]-5(6Н)-ones, which were separated by column chromatography.

Thiazoloquinazoline scaffold constitutes a promising source of inspiration for the synthesis of novel bioactive molecules. The current review article summarizes the most recent synthetic routes toward thiazoloquinazoline derivatives, published between the years 1983 and 2016. According to the position of fusion between thiazole and quinazoline rings, the thiazoloquinazoline derivatives in this review were classified into seven major types.

A summary of the most recent approaches toward synthesis of thiazolo[3,2-b][1,2,4]triazole system is reported. The microreview covers the latest selected examples on the synthesis of thiazolo[3,2-b][1, 2, 4]triazoles via condensation, annulation of a multiple bond or thiirane ring, as well as C–H functionalization of thiazole moiety.

2-(4-Oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)acetonitrile was used as the key intermediate for the synthesis of polyfunctionally substituted heterocycles (e.g., pyrazoles, pyridine, tetrazole, thiazoles, thiophenes, and chromene) incorporating the pyrazolo[3,4-d]pyrimidin-4-one moiety. Representative compounds of the synthesized series were tested and evaluated as antioxidants. Two of the tested compounds (pyrazole and thiophene derivatives) showed antioxidant activity nearly equal to that of ascorbic acid.

A novel multicomponent synthesis of highly substituted pyrazolo[1,5-a]pyrimidine derivatives starting from simple and readily available reactants is described. Three-component condensation of 4-(thiazol-2-yldiazenyl)-1H-pyrazole-3,5-diamine with triethyl orthoformate and carbonyl compounds or nitriles containing an activated methylene group gave substituted pyrazolo[1,5-a]pyrimidines. An analogous reaction of 4-(thiazol-2-yldiazenyl)-1H-pyrazole-3,5-diamine with ethyl acetoacetate and benzaldehyde in an effective one-pot process furnished ethyl 2-amino-5-methyl-7-phenyl-3-(thiazol-2-yldiazenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylate.

In the present study, the possibility of converting [5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazol-2-yl]amine to 2-halothiazoles and an azo compound via diazotation of the amine functionality was demonstrated. It was found that the reaction of [5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazol-2-yl]amine with acyl and sulfonyl chlorides leads to products resulting from substitution exclusively at the exocyclic nitrogen atom. The halogen atom at position 2 of thiazole ring is substituted by S-nucleophiles or hydrogen atom upon catalytic hydrogenation on Pd/C. 2-Bromo-5-(1,1,2,2-tetrafluoroethoxy)-4-phenylthiazole was successfully employed in the synthesis of the corresponding α-thiazolylbenzyl alcohol and 2-formylthiazole via conversion to a organomagnesium intermediate. The stability of the tetrafluoroethoxy group in the above transformations was demonstrated.

The reaction of 2-chloro-N-phenacylpyridinium salts with diazonium salts in the presence of bases was studied for the first time. It was demonstrated that this reaction leads to the formation of [1,2,4]triazolo[4,3-a]pyridinium salts. It was shown that substitution of the pyridine with a thiazole moiety leads to a similar cyclization.

A series of previously unreported thiazole derivatives, 4-(1H-1,2,3-triazol-4-yl)-1,3-thiazole-2-amines, was prepared by the Hantzsch reaction between the respective 1,2,3-triazole α-bromo ketones and (het)arylthioureas.

Quantum-chemical calculations were performed for the molecular structures of 1,2-azoles (pyrazole, isoxazole, isothiazole), 1,3-azoles (imidazole, oxazole, thiazole), and the corresponding intermediates of electrophilic substitution reactions (with protons as the model electrophiles): azolium ions, bipolar ions (ylides/carbenes), cationic σ-complexes, as well as activation energy values were calculated for the decomposition of ylides. The calculations were performed for gas phase and aqueous solutions according to the B3LYP method in a 6-31G(d) basis set, with corrections for the zero-point vibration energy. The solvation effects were taken into account by using the overlapping spheres model (IEFPCM). The results of the calculations explained some features of electrophilic substitution in azoles according to two alternative mechanisms: the classical addition-elimination with cationic σ-complex intermediates, and the mechanism of elimination-addition that involves ylides (carbenes) as key intermediates.

The reaction of 4,5,6,7-tetrahydro-1-benzothiophene derivatives with ethyl acetoacetate gave oxobutanamide derivatives. The reactivity of these products towards some chemical reagents was studied to afford new heterocyclic derivatives. The cytotoxicity of the newly synthesized compounds was evaluated against three human tumor cells lines and three normal cell lines. The results showed that some of these compounds exhibit high inhibitory effects towards the three tumor cell lines and the normal cell lines.

A number of functionalized pyridine derivatives in which the pyridine ring is linked to triazole, thiadiazole, thiazole, and tetrazole moieties were synthesized by cyclization with carbon disulfide, phenylisothiocyanate, and sodium azide. Benzylation of the synthesized tetrazolylmethylpyridone derivative afforded the N(1)-benzylated product; its crystal structure is reported. The substituted fused tetracyclic pyridofuropyrimidine was synthesized by sequential reactions starting from the 2-pyridone derivative.

A method for the synthesis of [(thiazol-2-ylamino)methylene]bisphosphonic acids from (aminomethylene)-bisphosphonic acid through 3-N-unsubstituted (thioureidomethylene)bisphosphonic acid was proposed.

The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminothiazole in MeONa/MeOH at 60oC for 3 h gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]thiazole-5,10-dione in 64% yield. The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminobenzothiazole under the above-mentioned conditions gave 2-(benzo[d]thiazol-2-ylamino)-3-bromonaphthalene-1,4-dione in 64% yield, which on treatment with Na/THF or NaN 3 /acetone under reflux conditions gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]- benzothiazole-7,12-dione in 69 and 56% yields, respectively.

3-Aryl-2-chloropropanal was obtained by the reaction of arenediazonium chlorides with acrolein in the presence of copper(II) chloride. N-Aryl(2-pyridyl)-5-(R-benzyl)-1,3-thiazole-2-amines were formed in high yield by the reaction of these aldehydes with aryl- and 2-pyridylthioureas. The same compounds were obtained by the reaction of 5-(R-benzyl)-1,3-thiazole-2-amines with aniline.

The synthesis of new amino and alkoxy derivatives of thiazole-5-carbaldehyde, on the basis of which α,β-unsaturated ketones of the thiazole series were synthesized, are described in this paper. The possibility of obtaining chalcones and variation of substitution reactions in the thiazole ring has been shown.

A method has been developed for obtaining thioamides of 5-amino-2-aryl-2H-1,2,3-triazole-4-carboxylic acid. Their heterocyclization reactions with bifunctional reagents has been studied. New heterocyclic polycyclic ensembles have been synthesized containing a 1,2,3-triazole fragment, a thiazole, and a residue of the natural alkaloid cytisine.

It has been established that 5-vinyl-substituted (N-R,N-vinylaminomethyl)isoxazolo(thiazolo, thiadiazolo)pyrimidines are formed when tetrahydropyrido[3,4-d]pyrimidines, annelated with isoxazole, thiazole, and thiadiazole units are treated with terminal alkynes as a result of opening of the tetrahydropyridine ring. 7-Methoxymethyl-substituted [N-R,N-(dimethoxycarbonylvinyl)]aminoethyl-isoxazolo- and thiazolopyrimi-dines were obtained by reaction with dimethyl acetylenedicarboxylate (ADCE). Triazolo-pyrimidoazocine was obtained for the first time from tetrahydrotriazolopyrimidine and methyl propiolate.

Treatment of substituted 2-(2,4-dihydroxyphenacyl)thiazole and 2-(2,4-dihydroxyphenacyl)benzothiazole with propionic and isobutyric anhydrides gives the substituted 2-ethyl-and 2-isopropyl-7-acyloxychromones. The use of pivaloyl chloride gives 1-pivaloyloxy-2-hetarylstyrene derivatives.

The treatment of 3-[3-(dimethylamino)-1-oxo-2-propenyl]chromen-2-ones with 3-amino-4-cyanopyrazole gives 7-(2-oxo-2H-chromen-3-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitriles. The reaction of 3-(2-bromoacetyl)coumarins with 2-amino-4-(methoxycarbonylmethyl)thiazole and 2-amino-4-methylthiazole gives methyl 2-(6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b]thiazol-3-yl)acetate and 3-(2-methylimidazo[2,1-b]thiazol-6-yl)-2H-chromen-2-ones, respectively.