Objective  To design and synthesize novel non-sugar-based α-glucosidase inhibitors by a simple synthesis method and evaluate their inhibitory activity.

Methods  Indole-urea derivatives were synthesized by a onestep method using 1-amino-2-methylindoline hydrochloride and isocyanates as raw materials, the inhibitory activity of α-glucosidase was screened by enzyme activity assays, and the structure-activity relationship of the series of compounds was analyzed. Additionally, the pharmacokinetic properties and drug-likeness of compounds were predicted with the help of Discovery Studio software and the molinspiration website.

Results  In this study, 12 non-sugar-based indole-urea derivatives were synthesized simply and efficiently. Meanwhile, α -glucosidase inhibitory activity tests showed that the half-maximal inhibitory concentration (IC₅₀) values of compounds 4f-4l were significantly lower than those of the positive control, acarbose. The pharmacokinetic properties and druglikeness prediction results of compounds 4f-4l indicated that they conform to Lipinski's rule of five and exhibit good oral absorbability.

Conclusion  Indole-urea derivatives exhibit good α-glucosidase inhibitory activity, conform to drug-like properties, and can be used as lead compounds for the development of antidiabetic drugs.