New Building Blocks for July 2023_ChemScene - 코아사이언스

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Dipeptidyl peptidase-4 (DPP-4) is a serine protease and widely distributed throughout the body like expressed as an ectoenzyme on endothelial cells, present on the surface of T lymphocytes, and in a circulating form[1]. It is responsible for the rapid inactivation of the incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide (GIP) via cleavage of a dipeptide from the N-terminus of these oligopeptides. Inhibition of GLP-1 and GIP metabolic breakdown improves glycemic control in patients with type 2 diabetes, making DPP-4 a good therapeutic target. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. Approved DPP-4 inhibitors such as sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin have demonstrated their efficacy in improving glycaemic control, and major advantages including low risk of hypoglycemia and beneficial effect on weight[2-8]. 

A series of building blocks will be used as molecular fragments in the design of DPP-4 inhibitors.

[1] Journal of Medicinal Chemistry (2021), 64, 14, 9639-9648.
[2] Journal of Medicinal Chemistry (2020), 63, 13, 7108-7126.
[3] Journal of Medicinal Chemistry (2016), 59, 16, 7466-7477.
[4] Bioorganic & Medicinal Chemistry (2021), 46, 116354.
[5] Bioorganic & Medicinal Chemistry (2021), 29, 115861.
[6] European Journal of Medicinal Chemistry (2019), 180, 509-523.
[7] European Journal of Medicinal Chemistry (2018), 151, 145-157.
[8] European Journal of Medicinal Chemistry (2017), 141, 519-529.

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