A. Sandeep, Grewal Ajmer Singh, S. Neelam
Mar 5, 2021
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journal of applied pharmaceutical science
Abstract
of this article was presented at CUDC consortium and Summer School Conference at Chitkara University, India. __________________ Arora et al. / Journal of Applied Pharmaceutical Science 11 (Supp 1); 2021: 038-047 039 allosteric location of GK (Grewal et al., 2014; Pal et al., 2009b). Some of the benzamide derivatives reported recently as potent GK activators are shown in Figure 1 along with their GK activity (Bowler et al., 2013; Charaya et al., 2018; Ericsson et al., 2012; Grewal et al., 2019a, 2019b; Lei et al., 2015; McKerrecher et al., 2018; Park et al., 2013, 2014; Pike et al., 2011; Sjostrand et al., 2013; Wang et al., 2017). Based on the above-mentioned facts, few newer N-benzothiazol-2-yl benzamide correspondents were proposed as potential activators of human GK. MATERIALS AND METHODS All the chemicals were acquired from reputed companies, including Spectrochem, Sisco Research Laboratories Pvt. Ltd. (SRL), S.D. Fine-Chem, Merck, Fisher Scientific, and SigmaAldrich etc., and employed without purification. Melting points of the synthesized molecules were determined using the uncorrected Veego Model of melting point apparatus melting point device. Culmination of reaction was checked employing silica Gel-G Thin layer chromatography (TLC). IR spectra were obtained using “Shimadzu Fourier-transform infrared (FTIR) spectrophotometer” (employing “KBr pellet” procedure). “Avance-II (Bruker) 400 MHz NMR spectrophotometer” was employed for taking Proton nuclear magnetic resonance (1H-NMR) and Carbon nuclear magnetic resonance (13C-NMR) spectra consuming appropriate dutereated solvent and conferred in parts per million (δ, ppm) downfield from tetramethylsilane (internal reference). General procedure for preparation of designed molecules Dry benzoic acid (1 mmol) was added to a flat bottom flask fixed on a magnetic stirrer at constant temperature around 10°C. Excess of sulfurochloridic acid (8.0 ml) was added carefully and observed to avoid any escape. When all the acid was liquefied and the exothermic response terminated, the flat bottom flask was heated at 70–80°C using water bath for 2 hours, followed by cooling. The materials of the flask were poured into crushed ice (150 g) with stirring and crystals of 3-(chlorosulfonyl)benzoic Figure 1. Some of the recently reported benzamide derivatives as potent GK activators. Arora et al. / Journal of Applied Pharmaceutical Science 11 (Supp 1); 2021: 038-047 040 acid were filtered employing vacuum subsequent to cold water wash, followed by air drying. The precipitates prepared earlier (1 mmol) were then reacted with the corresponding aliphatic and aromatic amines (1 mmol) under reflux using acetone till completion of the reaction (observed using TLC), following cooling and drying of the precipitates. The different sulfonamides prepared earlier (1 mmol) were refluxed with sulfinyl chloride (1 mmol) for 3 hours and extra sulfinyl chloride was removed to obtain the analogous acid chlorides. Acid chlorides prepared earlier (1 mmol) were refluxed with 2-aminobenzothiazole (1.5 mmol). The end products obtained by evaporation of solvent were purified using recrystallization from ethanol (Grewal et al., 2017; Singh et al., 2017). N-(1,3-benzothiazol-2-yl)-3-(phenylsulfamoyl)benzamide (1) FTIR (KBr Pellets) ν cm−1: 3,867.78 (NH str.), 3,737.50 (NH str.), 3,432.08.46 (NH str.), 2,973.38 (CH str.), 1,642.58 (C=O str.), 1,558.12 (NH bend), 1,463.36 (C=N str.), 1,417.54 (C=C str.), 1,296.70 (SO2 asym. str.), 1,076.13 (SO2 sym. str.), 752.08 (CH bend), 667.04 (C-S str.); 1H-NMR (δ ppm, 400 MHz, Dimethyl sulfoxide (DMSO-d6)): 8.92 (s, 1H, NH), 8.24–8.52 (m, 4H, CH), 7.34–8.26 (m, 4H, CH), 6.88–7.32 (m, 5H), 2.58 (s, 1H, NH); 13C-NMR (δ ppm, DMSO-d6): 172.09 (C=N), 164.46 (C=O), 152.34 (C), 136.32 (C), 135.38 (C), 131.78 (CH), 130.02 (C), 128.32 (C), 127.13 (CH), 125.23 (CH), 123.43 (CH), 122.02 (CH), 119.17 (CH), 118.64 (CH). N-(1,3-Benzothiazol-2-yl)-3-[(2-chloro-4-nitrophenyl) sulfamoyl]benzamide (2) FTIR (KBr Pellets) ν cm−1: 3,836.20 (NH str.), 3,446.91 (NH str.), 2,928.28 (CH str.), 1,641.34 (C=O str.), 1,632.23 (NH bend), 1,551.35 (C=N str.), 1,464.11 (NO2 sym. str.), 1,413.94 (NO2 asym. str.), 1,299.66 (SO2 asym. str.), 1,079.66 (SO2 sym. str.), 684.36 (C-Cl str.), 667.10 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 9.04 (s, 1H, NH), 8.02–8.48 (m, 4H, CH), 7.54–8.11 (m, 4H, CH), 6.98–8.12 (m, 3H, CH), 2.46 (s, 1H, NH); 13C-NMR (δ ppm, DMSO-d6): 169.78 (C=N), 162.32 (C=O), 151.56 (C), 139.22 (C), 137.28 (C), 133.67 (C), 131.09 (CH), 130.88 (C), 129.07 (CH), 128.57 (C), 127.46 (CH), 126.27 (C), 125.18 (CH), 124.22 (CH), 122.24 (CH), 118.88 (CH), 115.16 (CH). N-(1,3-benzothiazol-2-yl)-3-(benzylsulfamoyl)benzamide (3) FTIR (KBr Pellets) ν cm−1: 3,755.80 (NH str.), 3,448.08 (NH str.), 2,996.40 (CH str.), 2,912.85 (CH str.), 1,659.53 (C=O str.), 1,429.38 (NH bend), 1,311.51 (SO2 asym. str.), 1,025.25 (SO2 sym. str.), 696.02 (CH bend), 527.06 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.98 (s, 1H, NH), 8.16–8.42 (m, 4H, CH), 7.68–8.32 (m, 4H, CH), 7.16–7.58 (m, 5H, CH), 6.24 (t, 1H, NH), 4.42 (d, 1H, CH2); 13C-NMR (δ ppm, DMSO-d6): 176.02 (C=N), 165.32 (C=O), 152.34 (C), 141.46 (C), 140.06 (C), 134.45 (C), 130.34 (C), 130.12 (CH), 127.24 (CH), 124.37 (CH), 122.10 (CH), 119.43 (CH), 117.13 (CH), 48.32 (CH). N-(1,3-Benzothiazol-2-yl)-3-(butylsulfamoyl)benzamide (4) FTIR (KBr Pellets) ν cm−1: 3,754.38 (NH str.), 3,448.26 (NH str.), 2,930.77 (CH str.), 2,962.66 (CH str.), 1,643.35 (C=O str.), 1,554.13 (NH bend), 1,464.82 (C=C str.), 1,415.35 (SO2 asym. str.), 1,076.78 (SO2 sym. str.), 666.78 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 9.08 (s, 1H, NH), 7.80–8.12 (m, 4H, CH), 7.63–8.38 (m, 4H, CH), 5.54 (t, 1H, NH), 4.08 (m, 2H, CH2), 2.62 (m, 2H, CH2), 1.78 (m, 2H, CH2), 1.08 (m, 3H, CH3); 13C-NMR (δ ppm, DMSO-d6): 174.46 (C=N), 164.98 (C=O), 152.49 (C), 139.58 (C), 135.13 (C), 131.23 (CH), 130.34 (CH), 129.22 (CH), 125.47 (CH), 124.78 (CH), 121.12 (CH), 119.32 (CH), 118.34 (CH), 115.66 (CH), 45.08 (CH), 34.25 (CH), 20.88 (CH), 15.46 (CH). N-(1,3-Benzothiazol-2-yl)-3-(methylsulfamoyl)benzamide (5) FTIR (KBr Pellets) ν cm−1: 3,798.48 (NH str.), 3,448.44 (NH str.), 3,017.57 (CH str.), 2,966.14 (CH str.), 1,654.21 (C=O str.), 1,598.09 (NH bend), 1,544.68 (C=N str.), 1,388.45 (SO2 asym. str.), 1,189.77 (SO2 sym. str.), 789.65 (CH bend), 665.88 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.88 (s, 1H, NH), 7.94–8.43 (m, 4H, CH), 7.45–8.16 (m, 4H, CH), 5.34 (t, 1H, NH), 2.44 (s, 3H, CH3); 13C-NMR (δ ppm, DMSO-d6): 175.36 (C=N), 165.23 (C=O), 153.02 (C), 139.14 (C), 135.35 (C), 133.89 (CH), 133.13 (C), 132.06 (CH), 128.98 (CH), 125.83 (CH), 124.24 (CH), 121.56 (CH), 119.18 (CH), 118.11 (CH), 33.29 (CH). N-(1,3-benzothiazol-2-yl)-3-[(2-methylphenyl)sulfamoyl] benzamide (6) FTIR (KBr Pellets) ν cm−1: 3,791.96 (NH str.), 3,456.56 (NH str.), 3,013.67 (CH str.), 2,912.67 (CH str.), 1,667.25 (C=O str.), 1,604.66 (NH bend), 1,578.56 (C=N str.), 1,345.34 (SO2 asym. str.), 1,103.78 (SO2 sym. str.), 850.55 (CH bend), 664.89 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.89 (s, 1H, NH), 8.08–8.43 (m, 4H, CH), 7.42–8.08 (m, 4H, CH), 6.44–7.25 (m, 4H, CH), 2.54 (s, 1H, NH), 2.43 (s, 3H, CH3); 13C-NMR (δ ppm, DMSO-d6): 175.69 (C=N), 166.96 (C=O), 152.68 (C), 139.46 (C), 138.12 (C), 135.42 (C), 134.08 (C), 134.87 (CH), 133.67 (C), 132.12 (CH), 129.61 (CH), 126.59 (CH), 124.32 (CH), 123.56 (CH), 121.27 (CH), 118.25 (CH), 18.37 (CH). N-(1,3-benzothiazol-2-yl)-3-[(4-bromophenyl)sulfamoyl] benzamide (7) FTIR (KBr Pellets) ν cm−1: 3,837.14 (NH str.), 3,732.98 (NH str.), 3,441.64 (NH str.), 2,974.87 (CH str.), 1,641.67 (C=O str.), 1,553.91 (NH bend), 1,464.33 (C=N str.), 1,415.88 (SO2 asym. str.), 1,296.76 (SO2 sym. str.), 809.70 (CH bend), 753.82 (C-Br str.), 665.74 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.75 (s, 1H, NH), 8.14–8.38 (m, 4H, CH), 6.85–8.03 (m, 4H, CH), 7.06–7.38 (m, 4H, CH), 2.59 (s, 1H, NH); 13C-NMR (δ ppm, DMSO-d6): 176.08 (C=N), 166.34 (C=O), 153.12 (C), 139.10 (C), 137.05 (C), 134.28 (C), 132.72 (CH), 130.06 (CH), 129.73 (CH), 127.32 (CH), 124.94 (CH), 121.74 (CH), 120.21 (CH), 116.36 (C). N-(1,3-benzothiazol-2-yl)-3-[(4-nitrophenyl)sulfamoyl] benzamide (e8) FTIR (KBr Pellets) ν cm−1: 3,870.59 (NH str.), 3,755.40 (NH str.), 3,452.66 (NH str.), 2,997.49 (CH str.), 1,708.27 (C=O str.), 1,429.03 (NO2 sym. str.), 1,362.55 (NO2 asym. str.), 1,311.98 Arora et al. / Journal of Applied Pharmaceutical Science 11 (Supp 1); 2021: 038-047 041 (SO2 asym. str.), 1,223.02 (SO2 sym. str.), 696.02 (CH bend), 526.51 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.84 (s, 1H, NH), 8.28–8.58 (m, 4H, CH), 7.89–8.17 (m, 4H, CH), 6.68– 7.85 (m, 4H, CH), 2.50 (s, 1H, NH); 13C-NMR (δ ppm, DMSO-d6): 174.24 (C=N), 165.89 (C=O), 153.12 (C), 143.04 (C), 139.16 (C), 137.32 (C), 134.04 (C), 133.89 (C), 129.82 (CH), 124.22 (CH), 121.01 (CH), 120.84 (CH), 119.25 (CH), 116.39 (CH). N-(1,3-benzothiazol-2-yl)-3-[(4-methylphenyl)sulfamoyl] benzamide (9) FTIR (KBr Pellets) ν cm−1: 3,868.16 (NH str.), 3,754.28 (NH str.), 3,448.36 (NH str.), 2,930.77 (CH str.), 1,643.31 (C=O str.), 1,553.03 (NH bend), 1,464.83 (C=N str.), 1,415.35 (CH bend), 1,300.62 (SO2 asym. str.), 1,076.79 (SO2 sym. str.), 717.52 (CH bend), 666.77 (C-S str.); 1H-NMR (δ ppm, 400 MHz, DMSO-d6): 8.76 (s, 1H, NH), 7.98–8.28 (m, 4H, CH), 7.32–7.75 (m, 4H, CH), 6.32–7.23 (m, 4H, CH), 2.51 (s, 1H, NH), 2.36 (s, 3H, CH3); 13C-NMR (δ ppm, DMSO-d6): 176.03 (C=N), 165.94 (C=O), 153.12 (C), 139.88 (C), 136.65 (C), 135.14 (C), 133.74 (C), 132.64 (C), 130.95 (CH), 129.18 (CH), 125.34 (CH), 124.04 (CH), 120.84 (CH), 119.23 (CH), 118.06 (CH), 25.98 (CH). N-(1,3-Benzothiazol-2-yl)-3-(propylsulfamoyl)benzamide (10) FTIR (KBr Pellets) ν cm−1: 3,450.06 (NH str.), 2,996.68 (NH str.), 2,912.98 (CH str.), 1,689.51 (C=O str.), 1,428.92 (NH bend), 1,311.73 (C=N str.), 1,023.65 (SO2 asym. str.), 950.47 (SO2 sym. str.), 696.27 (CH bend), 524.89 (C-S str.); 1H-NMR (δ ppm, 400 MHz,