The therapeutic potential of phosphatase inhibitors

New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

“…These results suggest that the compounds are cell-permeable and able to strengthen insulin signalling by interfering with downstream components of the insulin signal cascade. The observed structureeactivity relationships indicate that the trifluoromethylphenylimino group (7) can significantly contribute to promoting the insulinomimetic activity and bioavailability of this class of compounds, probably due to the greater lipophilicity of the CF 3 group compared to the methoxy group (8).…”

“…In 1 H NMR spectra of compounds 5 and 6, the presence of two singlets at 3.87e3.90 ppm and 5.10 ppm, attributable to the 5-CH 2 and NeCH 2 protons, as well as the typical para-disubstituted systems were diagnostic for the attribution of the structure. The disappearance of 5-CH 2 signal and the presence of the methylidene proton resonance (7.66e8.16 ppm) proved to be significant for the attribution of the 5-arylidene-2-arylimino-4-thiazolidinone (7,8) structures.…”

Calix[4]arene α-hydroxymethylphosphonic acids as potential inhibitors of protein tyrosine phosphatases

“…У цій роботі калікс [4] A number of bioorganic studies have been focused on searching for inhibitors of protein tyrosine phosphatases (PTPs) [1]. The PTPs superfamily consists of 107 members that can be divided into different classes, which include the classical receptor and non-receptor PTPs [2].…”

“…Because of their involvement in various cellular processes, such as growth and proliferation, differentiation and survival or apoptosis [3], these enzymes are considered to be promising targets for new drug discovery today. Increase in activity or expression of PTPs may promote development of cancer, diabetes, obesity, Alzheimer's disease, Noonan syndrome, and other diseases [1]. For example, one of the non-receptor enzymes, protein tyrosine phosphatase 1B (PTP1B) was found to be a negative regulator of insulin, as well as leptin signaling pathways [4].…”

Barbituric Acid Derivatives as Protein Tyrosine Phosphatase Inhibitors

“…for the treatment of such diseases, inhibition of PTPs constitutes a major theme of medicinal chemistry as well as of this study. 8 In this study, barbituric acid derivatives were synthesized by condensation of appropriate benzaldehyde derivatives and barbituric acid with minor modifications of a reported procedure (Scheme 1). 9 The desired products were obtained in > 90% yields except a few cases where the yields were 65 -80%.…”