title: Toward the development of chemoprevention agents. Part II: Chemo-enzymatic synthesis and anti-inflammatory activities of a new class of 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes.
abstract: A new series of optically pure 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes were designed and synthesized via a chemo-enzymatic combined method to develop new chemoprevention agents. Twenty-four of newly synthesized compounds significantly inhibited xylene-induced rat ear edema and exhibited comparable or better anti-inflammatory activities than the reference drug aspirin. Treatment of these anti-inflammatory agents did not prolong the tail bleeding time in rat. In addition, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes exhibited good membrane permeability based on in vitro Caco-2 cell monolayer permeability assay. Furthermore, some preliminary structure-activity relationships were further analyzed among these compounds. Taken together, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes may represent a new class of anti-inflammatory drugs with safer pharmacological profile.
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University, Beijing 100054, PR China.
authors.forename: Keli
authors.initials: K
authors.lastname: Gu
authors.forename: Lanrong
authors.initials: L
authors.lastname: Bi
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Jingfang
authors.initials: J
authors.lastname: Ju
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001241:Aspirin / Q000627:therapeutic use; D001760:Bleeding Time; D002463:Cell Membrane Permeability / Q000187:drug effects; D018890:Chemoprevention; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D006844:Hydrocarbons, Cyclic; D014992:Xylenes; D011493:Protein Kinase C; D001241:Aspirin; D010100:Oxygen