5-(1H-indolyl-3-methylene)-1,3-thiazolidinyl-4-one derivatives, and synthesis method and application thereof

Abstract

The invention relates to 5-(1H-indolyl-3-methylene)-1,3-thiazolidinyl-4-one derivatives, and a synthesis method and application thereof. By using ethanol and / or water as a solvent, substituted 2-substituted-imino-1,3-thiazolidinyl-4-one and 1H-indolyl-3-formaldehyde are subjected to reflux reaction under the catalytic condition of piperidine through intermolecular dehydration condensation reaction to form methylene linking group, thereby obtaining the 5-(1H-indolyl-3-methylene)-1,3-thiazolidinyl-4-one derivatives. The intermediate 2-substituted-iminothiazolidinyl-4-one is prepared by carrying out cyclization reaction on various monosubstituted ethyl thiocarbamide chloroacetates or chloroacetic acids in a low-boiling solvent under reflux conditions, and the intermediate 2-substituted-imino-3-substituted-1,3-thiazolidinyl-4-one is prepared by carrying out a green environment-friendly synthesis technique on various disubstituted symmetric thiocarbamides and chloroacetic acids. The bioactivity preliminary screening experiment result of all the target compounds on the enzyme molecular level indicates that the target products have certain inhibition activity on PTP1B and CDC25B to different degrees.

Description

Technical field [0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to a 5-(1H-indole-3-methylene)-1,3-thiazolidine-4-type derivative and a synthetic method and application thereof. Background technique [0002] In the regulation process of cell proliferation and signal transduction, protein tyrosine phosphatase (PTP) (Maccari, R.; Ottanà, R., Low molecular weight phosphotyrosine protein phosphatases asemerging targets for the design of novel therapeutic agents. Journal of medicinal chemistry 2012, 55(1), 2-22.) and protein tyrosine kinase (PTK) (1. Blume-Jensen, P.; Hunter, T., Oncogenic kinase signalling. Nature 2001 ,413,355-365; 2.Hunter,T.,Tyrosine phosphorylation:thirty years and counting.Current opinion in cell biology2009,21(2),140-146.) and their respective substrates together form a signal transduction network , Together maintain the balance of tyrosine protein phosphorylation, and participate in the regulation of cell g...

AI Technical Summary

Problems solved by technology

Compared with the hot scene of PTK inhibitor research, the research on PTP inhibitors did not improve until PTP1B was isolated and identified, and gradually attracted widespread attention. However, the drug has not been successfully marketed. One of the reasons is how to improve the ability to target PTP1B. The selectivity of the enzyme has always been a difficult problem to solve, which is due to the homology between PTP1B and many members of the PTP family, in which the sequence (HCX 5 RX) is a common feature of PTP1B and its family

[0003] There are many types and structural types of PTP1B inhibitors, ranging from vanadium metal complexes that can oxidize the Cys215 residue in the active site of PTP1B to selective small molecule inhibitors, from structures that mimic phosphate substrates to peptide analogs, From salicylic acid to various aryl oxalic acid derivatives to thiazolidinediones and isothiazolidinones with five-membered heterocyclic rings, the low permeability of cell membranes is one of the current research targets for PTP1B inhibitors. The bottleneck that is difficult to break through

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