title: Modifying tetramethyl-nitrophenyl-imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy.
abstract: With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L-amino acids (6a-o) were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 μmol/kg 6a-o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 μmol/kg. The correlation of the three-dimensional quantitative structure-activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain.
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yaonan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China ; Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000737:chemistry; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D048288:Imidazolines; D051546:Cyclooxygenase 2
keywords: 3D-QSAR; analgesic; anti-inflammatory; tetramethylimidazoline