N-[2-(5,5-Dimethyl-1,3-dioxane-2-yl)ethyl]amino acids: Their synthesis, anti-inflammatory evaluation and QSAR analysis

Abstract Developing novel anti-inflammatory drugs is increasingly important in modern pharmaceutical industry. In this work, the reactions of both amino acids and their methylesters with 3-(5,5-dimethyl-1,3-dioxane-2-yl)propanal ( 2 ) were performed to either directly provide the goal products N -[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acids ( 4a – s ) in 9–65% yields or provide the intermediates N -[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acid methylesters ( 3a – s ) in 78–87% yields. The saponification of 3a – s provided 4a – s in 80–89% yields. Using a xylene-induced ear edema model, the anti-inflammatory activities of these newly synthesized anti-inflammatory agents were evaluated. The results indicated that comparing to the vehicle control 17 out of 4a – s significantly inhibited the development of inflammation in mice ( p 4a – s exhibited an even higher anti-inflammatory activity than the standard reference drug aspirin ( p