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.
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.
Gu
Keli
K
College of Pharmaceutical Sciences, Capital Medical University, Beijing 100054, PR China.
Bi
Lanrong
L
Zhao
Ming
M
Wang
Chao
C
Ju
Jingfang
J
Peng
Shiqi
S
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
D000893:Anti-Inflammatory Agents; D006844:Hydrocarbons, Cyclic; D014992:Xylenes; D011493:Protein Kinase C; D001241:Aspirin; D010100:Oxygen