Synthesis, structural characterization, biological activity, and theoretical studies of some novel thioether‐bridged 2,6‐disubstituted imidazothiadiazole analogues

Abstract

In this study, thioether-bridged imidazo [2,1-b][1,3,4]thiadiazole derivatives that contained both imidazole and 1,3,4-thiadiazole (compounds 7a-7i and 8a-8i) were synthesized from the reactions of 2-amino-1,3,4-thiadiazole with phenacyl bromide (6a-6i) (at yields of 59% to 74%). The structure of the synthesized compounds was characterized using 1 H NMR, 13 C NMR, Fouriertransform infrared spectroscopy, elemental analysis, mass spectroscopy, and Xray diffraction analysis. Mycelial growth, mycelial growth inhibition, minimum inhibitory concentration, minimum fungicidal concentration, and lethal dose values against various plant pathogenic fungi were determined for all of the target compounds synthesized in the study. The test results showed that most of the compounds had moderate to good antifungal activity. In addition, the absorption, distribution, metabolism, excretion (ADME) parameters of the compounds were calculated, and it was observed that all of the compounds met the drug-likeness rules in general. Finally, using docking simulations, it was found that compounds 7h, 7i, 8h, and 8i showed high affinity to PDB ID:5TZ1, which is an CYP51 antifungal target structure.

Novel Thioether‐Bridged 2,6‐Disubstituted and 2,5,6‐Trisubstituted Imidazothiadiazole Analogues: Synthesis, Antiproliferative Activity, ADME, and Molecular Docking Studies

“…This situation in the 1 H‐NMR spectra shows that cyclization has taken place. This finding also shows parallelism with the data in the literature [31,41–46] …”

“…Insufficient or a complete lack of evaluation of a compound's ADME parameters and drug‐likeness properties leads to the failure of drug candidate compound before it even reaches the clinical trial stage [42,43,54] . In this context, various ADME parameters of the synthesized compounds were calculated in order to provide a solid foundation for this research and are listed in Table 3.…”

“…When the 13 C‐NMR spectra of compounds 7 – 15 are examined, the signals appearing in the range of 111.48–108.98 ppm and 145.52–145.28 ppm indicate that an imidazole‐thiadiazole fused ring has formed. These signals represent carbons C5 and C6 in imidazole [42,43] …”

Design, synthesis, and bioassay of novel 1‐(3‐chloropyridin‐2‐yl)‐5‐amino‐4‐pyrazole derivatives containing a 1,3,4‐thiadiazole thioether or sulfone moiety

“…In summary, thirty-four 1-(3-chloropyridin-2-yl)-5-amino-4-pyrazole derivatives containing a 1,3,4-thiadiazole thioether or sulfone moiety were designed and synthesized. All the title compounds were confirmed by 1 H NMR, 13 Germany). Mass spectrometry (MS) data were obtained by LC/MS (LC: 1100, MS: MSD Trap VL, Agilent Technologies, USA).…”

“…Pyrazole and 1,3,4-thiadiazole derivatives are an important class of nitrogen-containing heterocycles with a variety of biological activities (Figure 1) that contain antibacterial [5][6][7][8], anticancer [9,10], antifungal [11][12][13][14][15][16], insecticidal [17], and antiviral [18][19][20] properties and can be applied for active molecular design. In previous work [21,22], we found a series of 1,3,4-oxadiazole sulfide compounds with moderate to excellent antiviral activity.…”