Synthesis, structure and computational study of 5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine (Pesta) and its heterometallic π,σ-complex [Cu2FeCl2(Pesta)4][FeCl4].

Copper(I) π-coordination compounds with allyl derivatives of azoles are an interesting subject of current research, but CuI π-complexes with other transition-metal ions incorporated in the structure have been virtually uninvestigated. The present work is directed toward the synthesis and structural characterization of the novel heterometallic CuI/FeII π-complex di-µ2-chlorido-1:2κ2Cl;2:3κ2Cl-tetrakis[µ2-5-(prop-2-en-1-ylsulfanyl)-1,3,4-thiadiazol-2-amine]-1:2κ2N4:N3;1(η2),κN4:2κN3;2:3κ2N3:N4;2κN3:3(η2),κN4-dicopper(I)iron(II) tetrachloridoferrate(II), [Cu2FeCl2(C5H7N3S2)4][FeCl4] (1). The structure of the 5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine (Pesta, C5H7N3S2) ligand is also presented. The cationic substructure in 1 consists of one FeII and two CuI ions bridged by two chloride ions along with two σ,σ- and two π,σ-coordinated ligands, whereas the anionic part is built of isolated tetrahedral [FeCl4]2- ions. π-Coordination of the Pesta allyl group to the CuI ions prevents agglomeration of the inorganic Cu-Cl-Fe-Cl-Cu part into infinate chains. An energy framework computational analysis was performed for Pesta.

Synthesis, Molecular Docking and Biological Properties of Novel Thiazolo[4,5-b]pyridine Derivatives.

The synthesis, anti-inflammatory and antioxidant properties of novel 5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-one derivatives were discussed. Fused thiazolo[4,5-b]pyridin-2-ones were synthesized and modified at the N3, C5 and C6 positions of the main core in order to obtain the compounds with a satisfactory pharmacological profile. The synthesized compounds were preselected via molecular docking for further testing of their anti-inflammatory activity in vitro. Evaluation of novel compounds over the carageenin induced rat paw edema revealed strong anti-inflammatory action of some compounds including (thiazolo[4,5-b]pyridin-3(2H)-yl) propanenitrile (5) and thiazolo[4,5-b]pyridin-3(2H)-yl) propanoic acid (6) even exceeding the standard - Ibuprofen. The antioxidant activity of the synthesized compounds was measured in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.

Nitrileimines as an alternative to azides in base-mediated click [3 + 2] cycloaddition with methylene active nitriles.

Nitrileimines were implemented in practical click protocols with oxopropanenitriles for the straightforward 5-amino-1H-pyrazole synthesis via 1,3-dipolar cycloaddition. The reaction proceeds at room temperature in a short time with base catalysis and no chromatographic purification. High purity products were isolated by simple filtration. The selectivity of the reaction was observed.

Anticancer Activity Evaluation of New Thieno[2,3-d]pyrimidin-4(3H)-ones and Thieno[3,2-d]pyrimidin-4(3H)-one Derivatives.

Anticancer screening of several novel thienopyrimidines has been performed. The thienopyrimidine derivatives were synthesized from available starting materials according to the convenient synthetic procedures using a one-pot solvent-free reaction which gave a wide access to thienopyrimidine-derivative production. The synthesized compounds were preselected via molecular docking to be tested for their anticancer activity in NCI 60 cell lines. It was observed that some compounds showed remarkable anticancer activity. It was found that the most active compound among thieno[2,3-d]pyrimidine-4(3H)-ones is 2-(benzylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one, which possesses cytotoxic activity on almost all cancer cell lines with mean growth 51.01%, where the most sensitive was the melanoma cell line MDA-MB-435 with GP (Growth Percent) = -31.02%. The patterns of structure⁻activity that are important for further optimization of the structure and the creation of more selective and active anticancer agents were proposed.

Ligand-forced dimerization of copper(I)-olefin complexes bearing a 1,3,4-thiadiazole core.

As an important class of heterocyclic compounds, 1,3,4-thiadiazoles have a broad range of potential applications in medicine, agriculture and materials chemistry, and were found to be excellent precursors for the crystal engineering of organometallic materials. The coordinating behaviour of allyl derivatives of 1,3,4-thiadiazoles with respect to transition metal ions has been little studied. Five new crystalline copper(I) π-complexes have been obtained by means of an alternating current electrochemical technique and have been characterized by single-crystal X-ray diffraction and IR spectroscopy. The compounds are bis[µ-5-methyl-N-(prop-2-en-1-yl)-1,3,4-thiadiazol-2-amine]bis[nitratocopper(I)], [Cu2(NO3)2(C6H9N3S)2], (1), bis[µ-5-methyl-N-(prop-2-en-1-yl)-1,3,4-thiadiazol-2-amine]bis[(tetrafluoroborato)copper(I)], [Cu2(BF4)2(C6H9N3S)2], (2), µ-aqua-bis{µ-5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine}bis[nitratocopper(I)], [Cu2(NO3)2(C5H7N3S2)2(H2O)], (3), µ-aqua-(hexafluorosilicato)bis{µ-5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine}dicopper(I)-acetonitrile-water (2/1/4), [Cu2(SiF6)(C5H7N3S2)2(H2O)]·0.5CH3CN·2H2O, (4), and µ-benzenesulfonato-bis{µ-5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine}dicopper(I) benzenesulfonate-methanol-water (1/1/1), [Cu2(C6H5O3S)(C5H7N3S2)2](C6H5O3S)·CH3OH·H2O, (5). The structure of the ligand 5-methyl-N-(prop-2-en-1-yl)-1,3,4-thiadiazol-2-amine (Mepeta), C6H9N3S, was also structurally characterized. Both Mepeta and 5-[(prop-2-en-1-yl)sulfanyl]-1,3,4-thiadiazol-2-amine (Pesta) (denoted L) reveal a strong tendency to form dimeric {Cu2L2}2+ fragments, being attached to the metal atom in a chelating-bridging mode via two thiadiazole N atoms and an allylic C=C bond. Flexibility of the {Cu2(Pesta)2}2+ unit allows the CuI atom site to be split into two positions with different metal-coordination environments, thus enabling the competitive participation of different molecules in bonding to the metal centre. The Pesta ligand in (4) allows the CuI atom to vary between water O-atom and hexafluorosilicate F-atom coordination, resulting in the rare case of a direct CuI...FSiF52- interaction. Extensive three-dimensional hydrogen-bonding patterns are formed in the reported crystal structures. Complex (5) should be considered as the first known example of a CuI(C6H5SO3) coordination compound. To determine the hydrogen-bond interactions in the structures of (1) and (2), a Hirshfeld surface analysis has been performed.

New Convenient Strategy for Annulation of Pyrimidines to Thiophenes or Furans via the One-pot Multistep Cascade Reaction of 1H-Tetrazoles with Aliphatic Amines.

A versatile, convenient, efficient and high-yield synthetic method for 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[2,3-d]pyrimidin-4(3H)-ones, 2-R(3),R(4)-amino-5-R(1)-6-R(2)-thieno[3,2-d]pyrimidin-4(3H)-ones, and benzofuro[3,2-d]pyrimidin-4(3H)-ones preparation has been developed. The reaction proceeded without using solvents and included several steps. A variety of thieno[2,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives with substituents of different nature were obtained in high yields from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates, 3-(1H-tetrazol-1-yl)thiophene-2-carboxylates, and 3-(1H-tetrazol-1-yl)benzofuran-2-carboxylate after their treatment with aliphatic amines.

Synthesis of 1,2,3-Triazole Derivatives and Evaluation of their Anticancer Activity.

Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has been performed. The 1,2,3-triazole derivatives were synthesized from available starting materials according to convenient synthetic procedures. The antitumor activity of the synthesized compounds was tested in vitro by the National Cancer Institute in NCI60 cell lines. It was observed that some compounds showed slight anticancer activity. One of them possessed a moderate activity against melanoma, colon, and breast cancer. Standard COMPARE analysis was performed at the GI50 level.