title: 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.
authors.affiliation: a Department of Chemistry , Faculty of Science, King Abdulaziz University , Jeddah , Saudi Arabia.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Faidallah
authors.affiliation: a Department of Chemistry , Faculty of Science, King Abdulaziz University , Jeddah , Saudi Arabia.
authors.forename: Manal M
authors.initials: MM
authors.lastname: Al-Mohammadi
authors.affiliation: a Department of Chemistry , Faculty of Science, King Abdulaziz University , Jeddah , Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Alamry
authors.affiliation: a Department of Chemistry , Faculty of Science, King Abdulaziz University , Jeddah , Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Khan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005260:Female; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D013890:Thiourea / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011720:Pyrazoles; D013890:Thiourea
keywords: Antidiabetic activity; benzenesulfonylureas; fluorinated pyrazoles; molecular properties calculations; thioureas