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

• DOI: 10.1016/j.ejmech.2007.03.015
• Publication Date: 2007-04-05T11:11:57Z
• Authors: Xiangmin Li; Ming Zhao; Yu-Rong Tang; Chao Wang; Ziding Zhang; Shiqi Peng
• Keywords: Inflammation; Mice, Inbred ICR; Dose-Response Relationship, Drug; Anti-Inflammatory Agents, Non-Steroidal; Drug Evaluation, Preclinical; Quantitative Structure-Activity Relationship; Ear; Xylenes; 01 natural sciences; 3. Good health; 0104 chemical sciences; Dioxanes; Mice; Animals; Edema; Amino Acids

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<0.01). In particular, eight out of 4a-s exhibited an even higher anti-inflammatory activity than the standard reference drug aspirin (p<0.05-0.01). A QSAR analysis was performed by use of the molecular descriptors generated from e-dragon software. The predictive accuracy of the established QSAR model implies that it may be promising for screening the new derivatives of 2-position amino acid substituted 1,3-dioxanes as potential anti-inflammatory agents.