An efficient synthesis of mono-, di-, and tri-substituted 1,3-thiazoles employing functionalized thioamides as thiocarbonyl precursors.

Herein, we report an efficient strategy to synthesize functionalized 1,3-thiazoles using alkyl 2-amino-2-thioxoacetates. Thioamides, the synthetic precursors, react effortlessly with electrophilic reagents and are transformed into a series of phenyl-, methyl-, and acyl-substituted thiazoles with high functionalization at the 2nd position through sequential C-S/C-N bond formation. Rapid reaction times under metal-free mild conditions is a noteworthy feature of the reported protocol. Given the intriguing biological significance of the synthesized molecules, we further performed a comprehensive evaluation of their potency against the SARS-CoV-2 receptor (PDB ID: 7mc6) using a molecular docking approach, with binding scores ranging from -4.3 to -8.2 kcal mol-1.

Regioselective Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles and 1,3,4-Oxadiazoles via Alkyl 2-(Methylthio)-2-thioxoacetates and Alkyl 2-Amino-2-thioxoacetates.

An acid-catalyzed regioselective cyclization reaction of 2,5-disubstituted-1,3,4-thiadiazoles and 1,3,4-oxadiazoles has been developed. The synthetic precursors alkyl 2-(methylthio)-2-thioxoacetates/alkyl 2-amino-2-thioxoacetates react efficiently with acyl hydrazides, which transformed into a series of dehydrative and desulfurative products with employment of p-TSA and AcOH through a regioselective cyclization process. The alkyl 2-amino-2-thioxoacetate pathway generates excellent yield among the mentioned procedures. The reported methods are operationally simplistic and highly efficient with metal-free conditions and demonstrate significant functional group compatibility. Regioselective cyclized products were confirmed by single-crystal X-ray diffraction studies.

Unraveling the crystal structure, stability and drug likeness of 1,3,4-oxadiazole derivatives against Myelofibrosis: a combined experimental and computational investigation.

Herein, we report the synthesis and characterization of novel 1,3,4-oxadiazole derivatives, 2-methoxybenzyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C1) 2-methoxybenzyl 5-(2-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C2), and methoxybenzyl 5-(3-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C3) obtained through desulfurative cyclization reaction. The compound C2 was crystallized, and its crystal structure was elucidated using single-crystal X-ray diffraction technique. The Hirshfeld surface analysis was carried out to analyze, visualize and globally appreciate the weak interactions involved in crystal packing. These analyses were complemented by Quantum Theory of Atoms In Molecules (QTAIM) and Reduced Density Gradient (RDG), which allowed us to decipher the nature and types of attractive forces that contribute to maintain the crystal structure of the titled compound. Moreover, the ADME profile of the compound was predicted to assess its drug likeness. Finally, in silico studies were performed to explore the binding affinity of the compounds (C1-3) against Myelofibrosis through molecular docking and molecular dynamic simulations.Communicated by Ramaswamy H. Sarma.