Design, Synthesis, Biological Activity Studies Of Novel, Ethanesulfonamide PTP1B Inhibitors And Synthesis, Characterization Of Catena-Poly[[μ2-4,4’-bis(pyridin-3-ylethynyl)-1,1’-biphenyl-κ2N:N’]bisμ2-thiocyanato-κ2N:S)-bis(thi Ocyanato-κS)dimercury(Ⅱ

Diabetes is now the fourth or fifth leading cause of death in most developed countries,and with 194 million people suffering fromthe disease worldwide.Diabetes mellitus is a heterogeneous disorder and classified into four categories: Type 1,Type 2,other specific types and gestational diabetes mellitus,according to the etiology.Type 2 Diabetes constitutes 85-95% of all diabetes in developed countries,and an even higher percent in developing countries.Protein tyrosine phosphatase 1B(PTP1B)is a negative regulator of the insulin and leptin receptor pathways.PTP1 B plays a key role in cellular signaling and in several human diseases,particularly diabetes and obesity.The silencing of the PTP1 B gene in mice as well as the lack of the enzyme in PTP1B-knockout mice result in increasing insulin sensitivity and resistance to weight gain on a high-fat diet without causing any abnormality in the animals.Some studies indicate that PTP1 B which is a negative regulator of insulin,play a key role in developing insulin resistance.As a result,this enzyme has been considered a significant target for treatment of Type 2 Diabetes and obesity.However,there is no drug approved as PTP1 B inhibitor until now,and only two small molecule PTP1 B inhibitors entered clinical trials.Nearly all medicinal chemistry efforts have been severely hindered because the potent phosphotyrosine(pTyr)mimetics,such as bioisosteric nonhydrolyzable DFMP pTyr mimetics.Developing selective inhibitors of PTP1 B over other cellular PTPs is challenging task since the homology among PTPs is very high particularly TCPTP which shares nearly 80% homology to PTP1B(catalytic domains).In this paper,33 new compounds were designed using computer-aided drug design techniques,which set the ureido and ethanesulfonamides together in the inhibitors of PTP1 B.We selected 5 compounds with strong PTP1 B inhibitory activity to synthesis.The results showed that the five compounds showed better inhibition of PTP1 B relative to TCPTP,SHP1,SHP2 and LAR.The synthesis of the metal-organic framework(MOFs)has attracted wide attention over the past two decades due to the possibility of obtaining a variety of beautiful and interesting structures that are also very useful for the application of porous materials.In this paper,[Hg2(SCN)4(C26H16N2)]n was synthesized and characterized.In the title polymer,the two equivalent HgⅡ atoms are coordinated by one N atom of a bridging 4,40-bis(pyridin-3-ylethynyl)-1,10-biphenyl ligand,two S atoms of two thiocyanates and one N atom of a thiocyanate,giving rise to a distored tetrahedral coordination environment.The result of the mode of the organic ligands is the formation of zigzag sheets connected via bridging thiocyanate ligands.