Synthesis and anti-inflammatory evaluation of 4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives. Part 3.
Mast cells, neutrophils and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel anti-inflammatory agent, we have synthesized certain 4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives and evaluated their anti-inflammatory activities by reaction of 3,4-dichlorofuro[2,3-b]quinoline with appropriate Ar-NH(2) or Ar-OH. Compounds 6a and 15 were proved to be more potent than the reference inhibitor, mepacrine for the inhibition of rat peritoneal mast cell degranulation with IC(50) values of 6.5 and 16.4 microM, respectively. Compounds 2b, 6a, 10, and 15 also showed potent inhibitory activity (IC(50)=7.2-29.4 microM) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. These results also indicated that oxime derivatives are more potent than the respective ketone precursors (6a> or =2a; 7a> or =3), and the substituent such as Me at the oxime decreased inhibitory activity (6a> or =6b; 7a> or =7b). Among these derivatives, compound 6a showed the most potent activity with IC(50) values of 6.5-11.6 microM for the inhibition of mast cell degranulation and neutrophil degranulation.
Chen
Yeh-Long
YL
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan. eloch@cc.kmu.edu.tw
Chen
I-Li
IL
Lu
Chih-Ming
CM
Tzeng
Cherng-Chyi
CC
Tsao
Lo-Ti
LT
Wang
Jih-Pyang
JP
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D015550:Cell Degranulation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020128:Inhibitory Concentration 50; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
C492852:1-(4-(3-chlorofuro(2,3-b)quinolin-4-ylamino)-phenyl)ethanone oxime; D000893:Anti-Inflammatory Agents; D010091:Oximes; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha