Synthesis, biological evaluation, molecular docking and in silico ADME studies of phenacyl esters of N -Phthaloyl amino acids as pancreatic lipase inhibitors

摘要

In continuation of our previous study, a series of phenacyl esters ofN-phthaloyl amino acids were synthesized and screened for theirin vitropancreatic lipase inhibitory activity.N-phthloylation of amino acids and subsequent esterification with different phenacyl bromides in presence ofN,N-Dimethylformamide (DMF) afforded the corresponding phenacyl esters in quantitative yields. The synthesized compounds were found to have potentin vitropancreatic lipase inhibitory activity in 0.9–2.5?μM range. The most active compound 2‐(4‐bromophenyl)‐2‐oxoethyl 3‐(1,3‐dioxo‐2,3‐ dihydro‐1H‐isoindol‐2‐yl) propanoate (4g)displayed very good pancreatic lipase inhibitory activity with the IC50value 0.9?μM. To understand the enzyme inhibition and to ensure the lead likeness,in silicodocking and ADME studies were carried on title compounds. Thein vitropancreatic lipase inhibitory activities andin silicostudies suggested that thisN-phthaloyl phenacyl ester analogues could be a potential lead and may be taken to the next level of antiobesity drug development.