Also, the disparity between the activities of piperidinyl and morpholinyl derivatives shows that the oxygen atom in the morpholine molecule is important for the binding with a potential molecular target. This is probably caused by the fact that the oxygen atom can participate in the formation of hydrogen bonds in the drug-target site. Fig. 1 Chemical structures of compounds 22–25 Conclusions Our research showed that chemical character of the C-5 substituent significantly determines the antibacterial activity of the N2-aminomethyl derivatives of the SAR302503 cell line 1,2,4-triazole. This activity can be considerably increased by an introduction of an electron-withdrawing chlorine atom to the phenyl ring in the C-5 position.
In addition to this, the number of atoms which form the aminomethyl STA-9090 molecular weight substituent seems to be important. The activity of the obtained Mannich bases was particularly strong toward opportunistic bacteria. The antibacterial activity of some compounds was similar or higher than the activity of commonly used antibiotics such as ampicillin and cefuroxime. Experimental General comments All reagents and solvents were purchased from Alfa Aesar (Ward Hill, USA) and Merck Co. (Darmstadt, Germany). Melting points were determined using Fisher-Johns apparatus
(Fisher Scientific, Schwerte, Germany) and are uncorrected. The 1H-NMR and 13C-NMR spectra were recorded on a Bruker Avance spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) using TMS as an internal standard. The IR spectra (KBr) were obtained on a Perkin-Elmer 1725X FTIR spectrophotometer. Elemental analyses were performed on an AMZ 851 CHX analyzer (PG, Gdańsk, Poland) and the results were within ±0.2 % of the theoretical value. All the compounds were purified by flash chromatography (PuriFlash 430evo, Interchim, USA). Synthesis of thiosemicarbazide derivatives (4–6) Three derivatives of thiosemicarbazide: 1-benzoyl-4-(4-bromophenyl)thiosemicarbazide (4), 4-(4-bromophenyl)-1-[(2-chlorophenyl)carbonyl]thiosemicarbazide click here (5), and 4-(4-bromophenyl)-1-[(4-chlorophenyl)carbonyl]thiosemicarbazide
(6) were synthesized according to the procedure described earlier (Plech et al., 2011a). Their spectral and physicochemical properties were consistent with (Li et al., 2001; Oruç et al., 2004). Synthesis of 1,2,4-triazole derivatives (7–9) Appropriate thiosemicarbazides (4–6) were dissolved in 2 % solution of NaOH. Next, the resulting solution was heated under reflux for 2 h. After cooling, the reaction mixture was neutralized with HCl. The precipitated product was filtered off, washed with distilled water, and recrystallized from EtOH. 4-(4-Bromophenyl)-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (7) Yield: 87 %, CAS Registry Number: 162221-97-8. 4-(4-Bromophenyl)-5-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8) Yield: 83 %, m.p. 282–284 °C, 1H-NMR (250 MHz) (DMSO-d 6) δ (ppm): 7.08–7.76 (m, 8H, Ar–H), 14.03 (s, 1H, NH, exch. D2O).