5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.
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.
Maccari
Rosanna
R
Dipartimento Farmaco-Chimico, Università di Messina, Vl SS Annunziata, Messina, Italy. rmaccari@pharma.unime.it
Paoli
Paolo
P
Ottanà
Rosaria
R
Jacomelli
Michela
M
Ciurleo
Rosella
R
Manao
Giampaolo
G
Steindl
Theodora
T
Langer
Thierry
T
Vigorita
Maria Gabriella
MG
Camici
Guido
G
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*
D045162:Thiazolidinediones; D017027:Protein Tyrosine Phosphatases