Synthesis, Structure–Activity Relationship and Docking Studies of Substituted Aryl Thiazolyl Phenylsulfonamides as Potential Protein Tyrosine Phosphatase 1B Inhibitors

Abstract

28 to 1—not bad odds: Protein tyrosine phosphatase 1B (PTP1B) is a promising target for the treatment of type 2 diabetes. Aryl thiazolyl phenylsulfonamides were synthesized and screened against PTP1B in vitro. Compounds exhibiting >48 % inhibition were then evaluated in a streptozotocin‐induced (STZ) rat model of diabetes, identifying one compound with efficacy comparable to that of metformin. Finally, docking studies were used to explain the observed structure–activity relationships.

A Computer‐Driven Scaffold‐Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2‐a]quinoxaline Core

“…In this context, the research on PTP1B inhibition is an active field that aims to provide new insights into its function and therapeutic approaches with a plethora of inhibitors reported [23–27] . Scaffold‐hopping strategies, which aim to identify iso‐functional molecules with different main cores, form part of the current medicinal chemistry toolbox.…”

Synthesis, SAR and docking studies of substituted aryl phenylthiazolyl phenylcarboxamide as potential protein tyrosine phosphatase 1B (PTP1B) inhibitors

“…The key intermediate N ‐(2‐(trifluoromethyl))‐4, 5‐dihydrothiazol‐2‐amine (3d) of compound II was synthesized using 2‐trifluoromethyl aniline according to the procedure mentioned in the earlier reported paper (Varshney et al., ). Further, the intermediate 3d on reaction with 4‐methoxybenzoyl chloride gave the compound II .…”

“…These inhibitors although show high PTP1B‐binding affinity but contain less cellular potency because of poor membrane permeability which is associated with targeting active site by highly acidic phosphotyrosine mimetics (Maheshwari et al., ). In past, we have synthesized novel substituted aryl thiazolyl phenylsulphonamides as non‐phosphorous small molecule inhibitors of PTP1B using fragment‐based approach, where compound I (73.6% PTP1B inhibition at 10 μM) was found to be the most active PTP1B inhibitor among the series (Figure ) (Varshney et al., ). In continuation of our efforts to design more in vivo effective PTP1B inhibitors, we herein report further lead optimization of compound I using sub‐structural approach to identify PTP1B inhibitors with better in vitro and in vivo activities.…”

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Anti-oxidant and Anti-hyperglycemic Activity

“…Animals of control group were given an equal amount of 1.0 % gum acacia. The blood glucose level of each animal was determined just before the administration of standard drug and test samples (0 min) and thereafter at 30,60,90,120,180,240,300 and 1440 min. Food but not water was withdrawn from the cages during 0 to 300 min.…”

“…Effect of compound 6c and 7d on lipoprotein lipase activity in triton induced hyperlipidemic rat4.5. Molecular modeling studyThe knowledge about the 3D structure of the target may significantly add to the understanding of important interactions which in turn responsible for biological activity variation among the different ligands acting on the same target[29,30]. The predicted binding mode of compound 6c at LPA binding revealed that the nitrogen atom of indole ring makes H-bond contact with Glu-298 residue.…”