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A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C-NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a–f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of −7.7 to −8.7 kcal/mol for 3a–f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a–f ligands and the receptor’s active amino acid residues. The main aim of using in silco molecular docking was to rank 3a–f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a–f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a–f.

Recently, the development of nanocatalysts based on naturally occurring polysaccharides has received a lot of attention. Chitosan (CS), as a biodegradable and biocompatible polysaccharide, is considered to be an excellent template for the design of a hybrid biopolymer-based metal oxide nanocomposite. In this case, lanthanum oxide nanoparticles doped with chitosan at different weight percentages (5, 10, 15, and 20 wt% CS/La2O3) were prepared via a simple solution casting method. The prepared CS/La2O3 nanocomposite solutions were cast in a Petri dish in order to produce the developed catalyst, which was shaped as a thin film. The structural features of the hybrid nanocomposite film were studied by FTIR, SEM, and XRD analytical tools. FTIR spectra confirmed the presence of the major characteristic peaks of chitosan, which were modified by interaction with La2O3 nanoparticles. Additionally, SEM graphs showed dramatic morphological changes on the surface of chitosan, which is attributed to surface adsorption with La2O3 molecules. The prepared CS/La2O3 nanocomposite film (15% by weight) was investigated as an effective, recyclable, and heterogeneous base catalyst in the synthesis of pyridines and pyrazoles. The nanocomposite used was sufficiently stable and was collected and reused more than three times without loss of catalytic activity.

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (–8.1 ± 0.33 kcal/mol, –8.0 ± 0.35 kcal/mol, and –8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (–6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.

Novel N-arylpyrazole-containing enaminones 2a,b were synthesized as key intermediates. Reactions of 2a,b with active methylene compounds in acetic acid in the presence of ammonium acetate afforded substituted pyridine derivatives 5a-d. Enaminones 2a,b also reacted with aliphatic amines such as hydrazine hydrate and hydroxylamine hydrochloride to give bipyrazoles 8a,b and pyrazolylisoxazoles 9a,b, respectively. On the other hand, treatment of 2a,b with a heterocyclic amine and its diazonium salt yielded the respective [1,2,4]triazolo[4,3-a]pyrimidines 12a,b and pyrazolylcarbonyl[1,2,4]triazolo-[3,4-c][1,2,4]triazines 14a,b. Moreover, 2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (17) was prepared via reaction of enaminone 2a with aminothiouracil (15). Cyclocondensation of 17 with the appropriate hydrazonoyl chlorides 18a-c gave the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 21a-c. The cytotoxic effects of compounds 2b, 14a and 17 against human breast cell line (MCF-7) and liver carcinoma cell line (HEPG2) were screened and in both lines they showed inhibition effects comparable to those of 5-fluorouracil, used as a standard. The antimicrobial activity of some products chosen as representative examples was also evaluated.

Heteroaromatization of ethyl 2-cyano-4-oxo-2-(2-oxo-2-arylethyl)-4-arylbutanoates 3a,b with ammonium acetate gave ethyl 2,6-diarylisonicotinates 4a,b. Treatment of the latter with acetonitrile afforded novel beta-oxoalkanonitriles 6a,b. Reactions of 6a,b with phenyl hydrazine and hydroxylamine gave the corresponding pyridyl aminopyrazoles 8a,b and pyridyl aminoisoxazoles 10a,b, respectively.

Recent synthesis and utilization of enamines as precursors for heterocyclic and carbocyclic compounds are reviewed. Two general synthetic routes for preparation of enamines based on condensation and addition reactions. Enamines and azaenamines can be used as building blocks for carbocyclic, five-and six-membered heterocyclic as well as fused heterocyclic compounds.

Reactions of arene and heteroaromatics diazonium salts with active methylene compounds having cyano group have been illustrated to afford hydrazonoalkanenitriles with a range of substituents. Structural investigation for hydrazonoalkanenitriles has been made. Furthermore the reactivity of hyrazonoalkanenitriles towards nucleophilic and electrophilic reagents has been displayed.

Electrochemical partial fluorination of (4-arylthiazol-2-yl)acetonitriles was carried out to afford the corresponding (4-aryl-5-fluoro-5H-thiazol-2-ylidene)acetonitriles as main products in addition to (4-aryl-5-fluorothiazol-2-yl)acetonitriles and (4-arylthiazol-2-yl)fluoroacetonitriles. AMI calculations were conducted to compare the stability of the fluorinated products.