Synthesis of phenylpyridine derivatives and their biological evaluation toward dipeptidyl peptidase-4

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents

“…Due to lack of selectivity, Merck stopped working on α-amino acid & started focusing on β-amino acids, which light up several rings like piperazine and triazolopiperazine. Pyrimidinedione has better metabolic stability & shown potent, selective, and bioavailable DPP-4 inhibitor known as alogliptin [39,40]. Since after development of sitagliptin which was approved by the U.S Food and drug administration (FDA) in 2006, nine DPP4 inhibitors are already available in the market and have shown great efficacy with lower toxicity when compared with existing therapies (Figure 6).…”

“…Meanwhile, a newly developed potent class of antihyperglycemic drugs emerged out as selective DPP4 inhibitors with biaryl scaffolds moiety. These include derivatives of 4-phenylbenzimidazole, 4-phenyl-1,2-dihydroisoquinolin1-one, 4-phenylquinoline, 5-phenylpyridopyrimidinedione, 7-oxo-4-phenylpyrrolopyridine, 5-phenylimidazo-[1,2-a] pyrimidine, and phenylpyridine [35,40].…”

A First Attempt to Identify Repurposable Drugs for Type 2 Diabetes: 3D-Similarity Search and Molecular Docking

“…It is acknowledged that the performance of ROCS strongly depends on the selection of interrogation molecules. In this context, we choose the bioactive conformation of ((2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihidro [1,2,4]triazolo[4,3-A]pirazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2amine) co-crystallized ligand (PDB ID: 4FFW) [16] as template. Out of thirteen similarity parameters [18][19][20], TanimotoCombo was used as a reference to rank the chemicals from the DrugBank database.…”

“…The dipeptidyl peptidase 4 (DPP-4) proteolytic enzyme related to the pathophysiology of T2DM, is expressed on the surface of most cell types and is connected with signal transduction, immune regulation, and apoptosis. Also, it is responsible for the degradation of two incretins hormones such as glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic polypeptide (GIP) [4,5]. These two hormones are culpable for improving of insulin production and release.…”

“…Sitagliptin ((2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihidro [1,2,4]triazolo[4,3-A]pirazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine)), a highly selective DPP-4 inhibitor is used primarily for the T2DM treatment to improve glycemic control in addition to the benefits of reducing body weight, blood pressure, and albuminuria [8,9]. Despite these advantages, various side effects during treatment with sitagliptin have been observed such as hypersensitivity, pancreatitis, high triglyceride levels, some kidney problems, etc.…”