Identification of a Potential Lead Structure for Designing New Antimicrobials to Treat

Identification of a potential lead structure for designing new antimicrobials to treat infections caused by Staphylococcus epidermidis resistant strains

Supplementary material

Derivatives chemical identification

The structures of the compounds were elucidated by different methods including 1H Nuclear Magnetic Resonance (NMR) spectra obtained on a 300 MHz and 75 MHz, respectively, in a Varian Unity Plus instrument using tetramethylsilane as internal standard. The chemical shifts () reported in ppm and the coupling constants (J) in Hertz. The derivatives were also analyzed in a Perkin-Elmer Spectrum One FT-IR for obtaining the Fourier transform infrared (FT-IR) spectra. The solid samples were determined in potassium bromide (KBr) pellets. Melting points (m.p.) were determined with a Fisher-Johns apparatus. TLC was carried out using silica gel F-254 Glass Plate (20 x 20 cm). The EI-MS spectra were recorded using a Finingan MAT 711 A instrument. The ionization energy was 70 eV with the source 200o C and an accelerative voltage of 8 KV. Samples were introduced by the standard direct insertion probe. High-resolution data were obtained with the instrument using 10 000 resolution. All reagents and solvents used were analytical grade. We described all the identification values for the new derivatives below.

(3) 5-(1H-tetrazol-5-yl)-4-(phenylamino)thieno[2,3-b]pyridine, Yield: 62%, m.p.: 255 C, IR (KBr, cm-1): ( NH 3200-2400,  C=N 1590), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.67 (d, 6.0); 6.74 (d, 6.0); 8.98 (s); 7.50-7.27 (m); 10.06 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 294.24 (100).

(3a) 5-(1H-tetrazol-5-yl)-4-(3`-methoxyphenylamino)thieno[2,3-b]pyridine, Yield: 70%, m.p.: 240 C, IR (KBr, cm-1): ( NH 3200-2400,  C=N 1593), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.11 (d, 6.0); 6.85 (d, 6.0); 8.98 (s); 7.37-6.80 (m); 3.83 (s); 10.07 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 325.10 (100).

(3b) 5-(1H-tetrazol-5-yl)-4-(3`-methylphenylamino)thieno[2,3-b]pyridine, Yield: 60%, m.p.: 210 C, IR (KBr, cm-1): ( NH 3200-2400,  C=N 1555), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.64 (d, 6.0); 6.75 (d, 6.0); 9.07 (s); 7.38-7.04 (m); 2.85 (s); 10.36 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 309.10 (100).

(3c) 5-(1H-tetrazol-5-yl)-4-(3’-chlorophenylamino)thieno[2,3-b]pyridine, Yield: 70%, m.p.: 244 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1578), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.74 (d, 6.0); 6.90 (d, 6.0); 9.15 (s); 7.46-7.12 (m); 10.53 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 329.0770 (100).

(3d) 5-(1H-tetrazol-5-yl)-4-(3’-nitrophenylamino)thieno[2,3-b]pyridine, Yield: 67%, m.p.: 245 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1630); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.79 (d, 6.0); 6.97 (d, 6.0); 9.23 (s); 7.99-7.55 (m); 10.93 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 340.1021 (100).

(3e) 5-(1H-tetrazol-5-yl)-4-(3’-fluorophenylamino)thieno[2,3-b]pyridine, Yield: 70%, m.p.: 237 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1612); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.73 (d, 6.0); 6.89 (d, 6.0); 9.15 (s); 7.49-6.99 (m); 10.55 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 313.0940 (100).

(3f) 5-(1H-tetrazol-5-yl)-4-(3’-bromophenylamino)thieno[2,3-b]pyridine, Yield: 60%, m.p.: 256 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1574); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.76 (d, 6.0); 6.92 (d, 6.0); 9.12 (s); 7.37-7.17 (m); 10.48 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 373.0233 (100).

(3g) 5-(1H-tetrazol-5-yl)-4-(4`-methoxyphenylamino)thieno[2,3-b]pyridine, Yield: 75%, m.p.: 250 C, IR (KBr, cm-1): ( NH 3200-2400,  C=N 1615); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.59 (d, 6.0); 6.50 (d, 6.0); 9.01 (s); 7.32 (d, 8.7); 7.09 (d, 8.7); 3.91 (s); 10.19 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 325.36 (100).

(3h) 5-(1H-tetrazol-5-yl)-4-(4`-methyphenylamino)thieno[2,3-b]pyridine, Yield: 79%, m.p.: 255 C, IR (KBr, cm-1): ( NH 3200-2400,  C=N 1594), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.52 (d, 6.0); 6.53 (d, 6.0); 8.87 (s); 7.20 (d, 8.7); 7.11 (d, 8.7); 2.50 (s); 9.97 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 309.10 (100).

(3i) 5-(1H-tetrazol-5-yl)-4-(4’-chlorophenylamino)thieno[2,3-b]pyridine, Yield: 82%, m.p.: 242 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1612), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.67 (d, 6.0); 6.80 (d, 6.0); 9.17 (s); 7.48 (dd, 8.7; 2.1); 7.29 (dd, 8.7); 10.66 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ M+. 329.0826 (100).

(3j) 5-(1H-tetrazol-5-yl)-4-(4’-nitrophenylamino)thieno[2,3-b]pyridine, Yield: 60%, m.p.: 247 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1598); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.93 (d, 6.0); 7.16 (d, 6.0); 9.18 (s); 8.22 (d, 9.0); 7.16 (d, 9.0); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 340.1236 (100).

(3l) 5-(1H-tetrazol-5-yl)-4-(4’-fluorophenylamino)thieno[2,3-b]pyridine, Yield: 68%, m.p.: 275 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1615), 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.90 (d, 6.0); 6.65 (d, 6.0); 9.13 (s) - 8.91 (s); 7.18 (ddd, 6.3; 5.7; 2.7); 7.06 (dd, 6.3; 5.4); 10.57 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 313.0940 (100).

(3m) 5-(1H-tetrazol-5-yl)-4-(4’-bromophenylamino)thieno[2,3-b]pyridine, Yield: 75%, m.p.: 248 C, IR (KBr, cm-1): ( NH 3600-2400,  C=N 1616); 1H NMR (300 MHz, CDCl3,TMS,  in ppm) 7.70 (d, 6.0); 6.83 (d, 6.0); 9.15 (s); 7.60 (d, 9.0); 7.17 (d, 9.0); 10.57 (s); 3.50-5.00 (s), ESI-(+)-MS [M+H]+ 373.0538 (100).