Synthesis and biological evaluation of fluoropyrazolesulfonylurea and thiourea derivatives as possible antidiabetic agents

Abstract

Fluorinated pyrazoles, benzenesulfonylurea and thiourea and their cyclic sulfonylthiourea derivatives were prepared as hypoglycemic agents. The chemistry involves the condensation of 4-hydrazino benzenesulfonamide hydrochloride with fluorochalcones to give pyrazoline derivatives which upon oxidation with bromine water afforded corresponding pyrazoles. Reaction of pyrazolines with isocyanates and isothiocyanates give the corresponding ureas and thioureas. Subsequent cyclization of these thiourea derivatives with ethyl bromoacetate and α-bromoacetophenone yielded the 4-oxothiazolidines and thiazolines, respectively. Preliminary biological screening of the prepared compounds revealed significant antidiabetic activity. Molecular and biological properties calculations revealed favorable drug-like profiles of six compounds. The structure–activity relationship (SAR) and in silico drug relevant properties calculations (HBD, HBA, tPSA, miLogP, molecular weight, % ABS, drug-likeness and drug score) endorse that these compounds are potential leads for future drug discovery study.

Keywords:

• Antidiabetic activity
• benzenesulfonylureas
• fluorinated pyrazoles
• molecular properties calculations
• thioureas

Acknowledgements

The authors also acknowledge with thanks Science and Technology Unit, King Abdulaziz University for technical support. The authors wish to thank Department of Pharmacology, Faculty of Pharmacy, University of Alexandria for their helpful contribution and for laboratory facilities.

Declaration of interest

This project was supported by the NSTIP strategic technologies program in the Kingdom of Saudi Arabia-Project No: (12-ADV2732–03). The authors report no declarations of interest.

Supplementary material available online