Structure-activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives

Abstract

This paper presents the synthesis of some unique bi-heterocyclic hybrid molecules with a thiazole and an oxadiazole ring. The synthesis was initiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) to the corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydrazine hydrate in methanol. The treatment of the acid hydrazide, 2, with carbon disulfide gave the bi-heterocyclic nucleophile, 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol (3). Finally, the target compounds, 5a-o, were synthesized by stirring the nucleophile 3 with different electrophiles, 4a-o, in DMF using LiH as a base and an activator. The structures of the newly synthesized molecules were confirmed through spectroscopic techniques, such as IR, EI-MS, 1 H-NMR and 13 C-NMR. The structure-activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, urease and α-glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.

2‐Aminothiazole‐Oxadiazole Bearing N‐Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure‐Activity Relationship, and Binding Conformations

“…Compound 3 was prepared from ethyl 2‐(2‐amino‐1,3‐thiazol‐4‐yl)acetate ( 1 ) by following the already reported protocols [35] …”

“…For elemental analyses, Foss Heraeus CHNÀ O-Rapid instrument was used, and the theoret- 1) by following the already reported protocols. [35] Bright yellow amorphous solid; Yield: 90 %; m.p. 194 -195 °C; Mol.…”

Synthesis, anticholinesterase activity, molecular docking, and molecular dynamic simulation studies of 1,3,4‐oxadiazole derivatives

“…[33,34] Moreover, several derivatives of oxadiazole heterocycle bearing pyridine and thiazole rings with high inhibitory activity against metabolic enzymes, including human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II), AChE, BChE, and α-glucosidase have been reported. [35,36] Similarly, pyridine derivatives are other important biologically active heterocyclic compounds. Various pyridine derivatives are well known for their antioxidant, anti-inflammatory, antitubercular, and several other properties.…”