Protein Tyrosine Phosphatase 1B (PTP 1B), emerged as a highly validated, attractive target for the treatment of type 2 diabetes mellitus (T2DM) and obesity although no successful clinical drug molecule is reported till now. Thiazolidinedione (2,4-TZD) have been studied as hydantoin bioisosteres potentially free of the hypersensitivity reactions which are linked to the presence of the hydantoin system. 2, 4-TZD derivatives such as Pioglitazone have been marketed for the treatment of type 2 diabetes mellitus. Taking into consideration, the role of TZD derivatives as antidiabetic agents, we have designed novel biphenyl-substituted 2, 4-TZD derivatives as potential inhibitors of PTP 1B. Different N-substituted biphenyl-2,4-TZD derivatives were synthesized in multistep reaction by chloroacetylation of biphenyl, condensation with 4-hydroxy benzaldehyde, knoevenagel condensation with 2, 4-TZD and with substituted aryl halide followed by hydrolysis to get the title compounds. Designed compounds were synthesized in the laboratory and evaluated for their in-vitro PTP 1B inhibitory and antihyperglycemic activity. The results obtained from the study were encouraging and we identified few potent lead molecules showing good to moderate inhibition as well as good antihyperglycemic activity in the animal model of T2DM.

Design, synthesis and biological screening of novel 2, 4 thiazolidinedione derivatives as PTP 1B inhibitors for the management of type 2 diabetes mellitus

ACS Spring Meeting 2021

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