Zhi, Ying published the artcile4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B, Name: Ethyl 3-(dimethylamino)acrylate, the publication is Bioorganic & Medicinal Chemistry (2014), 22(14), 3670-3683, database is CAplus and MEDLINE.
Protein tyrosine phosphatase 1B is a neg. regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from the previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10-fold selectivity over a panel of PTP’s. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and mol. modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, the study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacol. properties over previously described PTB1B inhibitors and warrant further preclin. studies.
Bioorganic & Medicinal Chemistry published new progress about 924-99-2. 924-99-2 belongs to esters-buliding-blocks, auxiliary class Alkenyl,Amine,Aliphatic hydrocarbon chain,Ester, name is Ethyl 3-(dimethylamino)acrylate, and the molecular formula is C13H10N2S, Name: Ethyl 3-(dimethylamino)acrylate.
Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics