title: QSAR study of some anti-hyperglycaemic sulphonylurea drugs.
abstract: Sulphonylureas are widely used anti-hyperglycaemic drugs for the treatment of type 2 diabetes. The only published quantitative structure-activity relationship (QSAR) models for sulphonylurea drugs have been found to be questionable, for a number of reasons. We have re-analysed the human anti-hyperglycaemic potencies, acute mouse intraperitoneal toxicities (LD50) and plasma protein-binding abilities of the 15 drugs using multiple linear regression and obtained good QSAR models for each endpoint. The obtained QSARs all comply well with the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Validation of (Q)SARs. We could not carry out external validation of our models for acute toxicity and plasma protein-binding because of the very small datasets available.
authors.affiliation: a School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University , Liverpool , UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Dearden
authors.forename: M
authors.initials: M
authors.lastname: Hewitt
authors.forename: P H
authors.initials: PH
authors.lastname: Rowe
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D016014:Linear Models; D051379:Mice; D015999:Multivariate Analysis; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D001798:Blood Proteins; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds
keywords: QSAR; anti-hyperglycaemic activity; plasma protein-binding; potency; sulphonylureas; toxicity