Synthesis of sulfonylthioureas containing two carbon linker as potential antidiabetic drugs

Abstract

Target compounds (18a-s) from the series (morpholine, piperidine, N-methylaniline, 2,6-dimethylaniline and diethylamine) of novel sulfonylthioureas were designed and synthesized over three reaction steps using different appropriate synthetic methods. Nucleophilic substitutions were employed in order to incorporate amines, three different carbon linkers between amines and sulfonylthioureas moiety. Furthermore, nucleophilic substitution reaction was used to incorporate appropriate substituted isothiocynates as the final main step. Compounds (18a-s) were obtained in good to excellent yields and were characterized using a combination of 1H NMR, 13C NMR, IR and HRMS analysis. Compounds (18a-s) were evaluated for their antidiabetic activity against α-glucosidase and α-amylase. The in vitro screening results showed that most compounds had little to moderate activity against α-amylase at the concentrations of 60μM, 120μM and 240μM. When compounds were tested against α-glucosidase, they showed little to moderate antidiabetic activity at the concentrations of 60μM and 120μM but exhibited significant anti-diabetic activities at 240μM. Compounds that have a phenyl group substituent (18j, 18m, 18q, 18r and 18s with inhibition 70.21±5.97, 78±3.03, 76.33±2.03, 69.55±4.11 and 84.67±3.34 respectively at 240 μM) and a methyl group substituent (18q-s) exhibited stronger inhibition activity.