title: 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<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.
authors.affiliation: College of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Tang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Ziding
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004146:Dioxanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D021281:Quantitative Structure-Activity Relationship; D014992:Xylenes / Q000633:toxicity
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004146:Dioxanes; D014992:Xylenes; C025223:1,4-dioxane