Synthesis of Novel 3‐aryl‐1‐oxa‐2,8‐diazaspiro[4.5]dec‐2‐ene Derivatives and Their Biological Evaluation Against Protein Tyrosine Phosphatase 1B

Abstract

A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against protein tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of protein tyrosine phosphatase 1B.

Synthesis of 2-ethoxycarbonylthieno[2,3-b]quinolines in biomass-derived solvent γ-valerolactone and their biological evaluation against protein tyrosine phosphatase 1B

“…Our efforts to develop modulators of protein tyrosine phosphatases started from 1 H -2,3-dihydroperimidines. 9–14 Using the scaffold hopping strategy, 15,16 we developed 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-enes 11 as PTP1B inhibitors, bis-aryl amides 9 and benzo[ c ][1,2,5]thiadiazoles as SH2-Containing Protein Tyrosine Phosphatase-2 (SHP2) inhibitors. 13 We noticed that the scaffold of thieno[2,3- b ]quinolines showed high similarity with that of 1 H -2,3-dihydroperimidines and might provide novel scaffold to develop novel PTP1B inhibitors ( Fig.…”