Benzofuroxane reacts under Beirut reaction conditions with active methylene nitriles to give new 2-aminoquinoxaline-1,4-dioxides. Treatment of known 2-amino-3-cyanoquinoxaline-1,4-dioxide with chloroacetyl chloride afforded corresponding chloroacetamide useful for preparation of various heterocycles bearing quinoxaline-1,4-dioxide core system.

The design and synthesis of chemosensors that allows the selectively detection of heavy metal cations by complexation, is an area of ​​growing interest. The hydrazone functional group has been widely used in supramolecular chemistry due to its complexing capacity, its conjugated electrons and its simple methods of synthesis. In this way, a nitrogen system derived from the condensation of vanillin (aromatic aldehyde) and 2-hydrazino benzothyazol to give the corresponding hydrazone for the detection of Cu²⁺ was developed. Spectroscopic determinations demonstrate whether the complexing took place. The hidrazone showed a response in UV-vis spectroscopy and a color shift is observed with the naked eye. In addition, theoretical analysis based on the density functional theory (DFT) was realized. The geometries of the benzothiazole hydrazone derived from vanillin (ligand) and its analog Cu²⁺-ligand complex were optimized at the B3LYP/631+G(d,p) level of theory. The adsorption spectra of this molecular system were analyzed and compared with experimental data. Theoretical study of the structural, electronics and optical properties allowed to understand the chemical changes that the ligand suffers in the complexation process with the Cu⁺² ion.

Polyphenols are attracting increasing attention to the discovery of useful agents for the treatment of neurodegenerative diseases.

Thelesperma megapotamicum (Spreng.) Kuntze belongs to the family Asteraceae which is known to have a high antioxidant capacity.

The phytochemical investigation of T. megapotamicum revealed the presence of 1’-S-acetoxyeugenol isobutyrate (1), 1’-S-isobutyroxyeugenol isobutyrate (2), stigmasterol (3), b-sitosterol (4), lupeol (5), luteolin (6), eriodictyol (7), and marein (8), as major secondary metabolites. Compounds 1-5, and 7 were isolated for the first time from T. megapotamicum.

The neuroprotective activity of this species was studied by evaluating the inhibition in vitro of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and antioxidant capacity of the sub-extracts and of the major metabolites isolated from them. The AChE and BChE inhibition were determined by Ellman’s method and the antioxidant activity by DPPH assay.

The chloroform (IC₅₀ = 30.7 ± 1.5 μg/mL) and n-butanol sub-extracts (IC₅₀ = 60.3 ± 2.3 μg/mL) were the most active against BChE. Metabolites 1, 2 and 8, isolated from these sub-extracts, exhibited the highest activity against this enzyme, with IC₅₀ values of 59.0 ± 2.1 μM, 46.4 ± 1.2 μM, and 51.6 ± 2.3 μM, respectively.

The ethyl acetate (IC₅₀ = 19.6 ± 0.7 μg/mL) and n-butanol sub-extracts (IC₅₀ = 49.5 ± 2.2 μg/mL) showed an interesting antioxidant activity. Compounds 6, 7 and 8, obtained from these sub-extracts, were the most active, with IC₅₀ values of 19.1 ± 2.8 μM, 17.9 ± 1.2 μM, and 78.6 ± 1.7 μM, respectively.

The inhibitory activity against BChE and antioxidant capacity of the polyphenols present in T. megapotamicum highlight this species as a promising source of active metabolites for the development of agents for the treatment of neurodegenerative diseases.

New triethylammonium 6-amino-4-aryl-3-carbamoyl-5-cyano-1,4-dihydropyridine-2-thiolates were prepared in good yields by ternary condensation of malononitrile, aldehydes and monothiomalonamide (3-amino-3-thioxopropanamide) in the presence of Et₃N. The thiolates undergo S-alkylation under mild conditions to give new 1,4-dihydronicotinamides. Molecular docking studies were carried out in order to explore the interaction mechanism and to investigate suitable binding modes of the new compounds on the calcium channel proteins. Some of the compounds in experiments in silico were found to be more potent as calcium channel blockers than reference drug Nifedipine.

The synthesis of two novel and complex molecules tetrakis-tetrazole were synthesized via a Ugi-azide repetitive reaction from easily accessible starting materials in good yields. The use of orthogonal bifunctional reagents in isocyanide based multicomponent reactions (IMCR) allowed us the synthesis of structurally complex molecules in one pot manner. The molecules herein synthesized could have applications, such as chelating agents and organocatalysis.

A series of three 2,5-diketopiperazine (DKP’s) were synthesized via one-pot process through the post-IMCR-transformation strategy. This strategy emphasizes the role of orthogonal bifunctional reagents in the IMCR process to increase their synthetic potential, allowing us accessing a synthetic platform from which it is possible to obtain privileged heterocyclic peptidomimetics via lactamization reaction.

Upon treatment with chloroacetyl chloride, 3-aminothieno[2,3-b]pyridines gave the corresponding chloroacetamides. The latter readily react with sodium thiosulphate to afford water soluble S-alkylthiosulphates with pharmacophoric heterocyclic units.

5-Amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile, prepared by reaction of malononitrile dimer with hydrazine, smoothly react with chloroacetyl chloride to afford 2-chloro-N-(4-cyano-3-(cyanomethyl)-1H-pyrazol-5-yl)acetamide in good yield. The latter easily react with 3-cyanopyridine-2-thiolates to give hybrid molecules bearing nicotinonitrile and pyrazole units.

N,N'-diphenyldithiomalonamide (dithiomalondianilide) smoothly reacts with various Michael acceptors to give either stable Michael adducts or products of their further heterocyclization. The structure of the products was confirmed by 2D NMR experiments and X-ray data. The mechanisms of the reactions are discussed.

A series of N-(thieno[2,3-b]pyridin-3-yl)cyanoacetamides were prepared by reaction of 3-aminothieno[2,3-b]pyridines with 1-cyanoacetyl-3,5-dimethytlpyrazole. Upon treatment with alkali, N-(2-alkoxycarbonylthieno[2,3-b]pyridin-3-yl)cyanoacetamides undergo Camps-type cyclization to give dipyridothiophenes. The relative stability of their tautomers was estimated by quantum chemical calculations. In contrast, cyclization of 3-(2-cyanoacetamido)thieno[2,3-b]pyridine-2-carboxamides lead to the formation of pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines.