title: 5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.
abstract: 4-(5-Arylidene-2,4-dioxothiazolidin-3-yl)methylbenzoic acids (2) were synthesized and evaluated in vitro as inhibitors of PTP1B and LMW-PTP, two protein tyrosine phosphatases (PTPs) which act as negative regulators of the metabolic and mitotic signalling of insulin. The synthesis of compounds 2 represents an example of utilizing phosphotyrosine-mimetics to identify effective low molecular weight nonphosphorus inhibitors of PTPs. Several thiazolidinediones 2 exhibited PTP1B inhibitory activity in the low micromolar range with moderate selectivity for human PTP1B and IF1 isoform of human LMW-PTP compared with other related PTPs.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Vl SS Annunziata, Messina, Italy. rmaccari@pharma.unime.it
authors.forename: Rosanna
authors.initials: R
authors.lastname: Maccari
authors.forename: Paolo
authors.initials: P
authors.lastname: Paoli
authors.forename: Rosaria
authors.initials: R
authors.lastname: Ottanà
authors.forename: Michela
authors.initials: M
authors.lastname: Jacomelli
authors.forename: Rosella
authors.initials: R
authors.lastname: Ciurleo
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Manao
authors.forename: Theodora
authors.initials: T
authors.lastname: Steindl
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Vigorita
authors.forename: Guido
authors.initials: G
authors.lastname: Camici
mesh_terms: D001665:Binding Sites; D008958:Models, Molecular; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D045162:Thiazolidinediones; D017027:Protein Tyrosine Phosphatases