16 Here we

report the facile synthesis, characterization and biological evaluation of novel N-alkyl-2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl)benzamides Metformin datasheet having novel substitution groups at the fourth position of the 1,2,6-thiadiazine ring (see Scheme 1). Melting points were determined in open capillary tubes and are uncorrected. All the chemicals and solvents used were laboratory grade. IR spectra were recorded on a Shimadzu-8400 FT-IR spectrometer using KBr disc. 1H NMR spectra were recorded on a Brucker 300 MHz spectrometer using TMS as an internal standard in CDCl3 and DMSO-d6, 13C NMR spectra were recorded on DPX 200 Brucker FT-NMR. Mass Spectra were obtained using a Hewlett–Packard 5989, Quadrapole Mass Spectrometer and a LC–MS Perkin Elmer API 165. Elemental analysis was performed on a Perkin Elmer 2400 Series II instrument. Methyl

2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl) benzoate was synthesized as previously reported.17 2-(2, 4-dioxopentan-3-yl) benzoic acid (0.072 mol) and sulfamide (0.072 mol) were dissolved in methanol (70 ml). Anhydrous hydrogen chloride gas was bubbled into the mixture until the temperature increased to 50 °C. The contents of the reaction were then refluxed for 3 h. The reaction mixture was cooled, filtered and the filtrate was concentrated under reduced pressure. The ester was isolated and hydrolyzed with NaOH (0.138 mol) in water (200 ml), the contents were heated at 70 °C for 2.5 h. The reaction progress was monitored by TLC ethyl acetate/hexane (80:20 Rf = 1/2). The reaction mixture was cooled and acidified using concentrated HCl to get the Cobimetinib order crude acid as an oil. To this oily residue was added a solution of methanol:ethyl acetate (10 ml) (1:9) which yielded a white colourless solid. 2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl)benzoic

acid (1) (5.0 g, 0.017 mol) and carbonyldiimidazole (CDI) (2.89 g, 0.017 mol) in 50 ml of dry tetrahydrofuran was stirred for 30 min at room temperature. The aliphatic or aromatic amines were then added slowly and the solution was stirred for 12 h at room temperature. The solvent was then completely evaporated and the tuclazepam residual mass was treated with 5% HCl (25 ml) and stirred for 1 h. The precipitates (pale yellow to light brown) were filtered and then recrystallized from a solution of water:ethanol (1:1) at room temperature. The elemental analysis, NMR and mass spectrometry data for compounds 2a–j follow: Mol. Wt: 335.42,M.P.: 192–195 °C; Yield 79% Rf 0.80; IR (cm−1): 1683(C]O amide), 3243 (N–H), 1164, 1317 (>S]O); 1505 (C]N); 3444 (NH–C]O): 1H NMR (δppm): 1.98 (s, 6H, Di-Methyl), 0.94 (t, 3H, –CH2–CH3), 1.36 (m, 2H, –CH2–CH3), 1.53 (m, 2H, –CH2–CH2–), 3.39 (m, 2H, –NH–CH2–), 7.21–7.65 (m, 4H, Ar–H), 8.1 (s, –C]O–NH–); Elemental analysis for C16H21N3O3S; Calculated: C, 57.24; H, 6.26; N, 12.52; O,14.