Design and synthesis of DPP-4 inhibitor for the treatment of type 2 diabetes

Design and Synthesis of Backbone-Fused, Conformationally Constrained Morpholine-Proline Chimeras

“…The salt was then dissolved in EtOH (2.4 mL), triethylamine (101 μL, 716 μmol) was added at r.t., and the solution was stirred for 16 h. The solvent was evaporated, sat. Na 2 CO 3 was added, the resulting mixture was extracted with CH 2 Cl 2 (3 × 20 mL), the combined organic phases were dried with anhydrous MgSO 4 (27). To a solution of aldehyde 19 (400 mg, 1.28 mmol) in THF (12.8 mL) were added dropwise at 0°C LaCl 3 •LiCl solution (638 μL, 383 μmol, 0.6 M) and then methyl magnesium chloride (468 μL, 1.4 mmol) dropwise at the same temperature.…”

Synthesis, In vitro and Docking Studies of New Flavone Ethers as α‐Glucosidase Inhibitors

“…Molecular docking studies were performed to gain insight into the most probable binding conformation of flavone ether derivatives (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), which in return explains the reason for their potency. Docking studies had been carried out using a-glucosidase structure obtained from homology modelling as crystal structure for a-glucosidase of S. cerevisiae is still not available (59).…”

“…Docking studies carried out on all flavone ethers (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) had provided us with some good results, which best explain the compounds in vitro. Important structural feature like ether linkage and substitution on the compounds' side chain were observed closely to further rationalize the inhibition activity.…”

“…This is supported by projection of World Health Organization (WHO) projection, which predicts diabetes to become the seventh leading cause of death worldwide by 2030 (7). Type II diabetes mellitus that is common in developed countries is characterized by impaired insulin secretion and reduced insulin sensitivity (8)(9)(10)(11)(12). One of the ways to reduce type II diabetes mellitus is by suppressing absorption and digestion of dietary carbohydrates.…”

“…A simple nucleophilic substitution reaction takes place between 3 0 hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3 0 hydroxyflavone (2) and the newly synthesized flavones (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were being evaluated for their ability to inhibit activity of a-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC 50 values ranging between 1.26 and 36.44 lM as compared to acarbose (IC 50 = 38.25 AE 0.12 lM).…”