The synthesis of 5-[(6-morpholin-4-ylpyridin-3-yl)amino]methyl-1,3,4-oxadiazole-2-thiol (7) was carried out from the reaction of hydrazide 4 with carbon disulfide in the presence of potassium hydroxide. An evidence for the formation of 7 is the absence of the signals corresponding to hydrazide
function in the FT-IR and 1H NMR spectra. The D2O exchangeable signal observed at 13.45 ppm was attributed to the SH proton located at the position-2 of 1,3,4-oxadiazole ring. The reaction of 7 with phenylpiperazine in the presence of formaldehyde afforded the corresponding Mannich base, 5-[(6-morpholin-4-ylpyridin-3-yl) amino]methyl-3-[(4-phenylpiperazin-1-yl)methyl]-1,3,4-oxadiazole-2(3H)-thione (8). In NMR spectra of 7, the presence of the peaks belonging to 4-phenylpiperazine nucleus confirmed the Mannich reaction. The synthesis of N′-[(5-(4-chlorophenyl)-3-phenyl-1,3-thiazol-2(3H)-ylidene]-2-(6-morpholin-4-ylpyridin-3-yl)aminoacetohydrazide INK 128 ic50 (10) obtained from the cyclocondenzation reaction between 4-chlorophenacyl bromide and compound 9 that was obtained by the treatment of hydrazide 4 with phenylisothiocyanate.
On the other hand, the treatment of the same intermediate 9 with ethyl bromoacetate resulted in the formation of 2-[(6-morpholin-4-ylpyridin-3-yl)amino]-N′-(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)acetohydrazide 13. The OSI-906 supplier structures of these compounds were confirmed on the basis of FT-IR, EI-MS, 1H NMR, 13C NMR spectroscopic methods, and elemental analysis. The basic treatment of intermediate 9 afforded Protein tyrosine phosphatase 5-[(6-morpholin-4-ylpyridin-3-yl)methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (11), while the cyclization of 9 in acidic media yielded 5-[(6-morpholin-4-ylpyridin-3-yl)methyl]-N-phenyl-1,3,4-thiadiazol-2-amine (12). In the 1H NMR spectrum of compound 11, the signal due to SH group was recorded at 13.91 ppm as an evidence of intramolecular cyclization. This group was seen at 2,857 cm−1 in the FT-IR spectrum of compound 11. Two NH signals were recorded
at 6.04 and 10.23 ppm as D2O exchangeable peaks in the 1H NMR spectrum of compound 12. In the 13C NMR spectra of compounds 11 and 12, other signals belonging to 1,2,4-triazole or 1,3,4-thiadiazole nuclei resonated at the chemical shift values consistent with the literature (Bektas et al., 2010, 2012). Furthermore, [M]+ ion peaks were observed at the related m/z values supporting the proposed structures. In addition, these compounds gave reasonable elemental analysis data. The newly synthesized compounds 3–13 were evaluated in vitro for their antimicrobial activities. The results are presented in the Table 1. Among the compounds tested, compound 8, which contains different heterocyclic moieties such as morpholine, pyridine, piperazine, and 1,3,4-oxadiazole important antimicrobial activity, was found to be active against all the Selleckchem GS-1101 microorganisms.