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-NH2 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 IC50 values of 6.5 and 16.4 muM, respectively. Compounds 2b, 6a, 10, and 15 also showed potent inhibitory activity (IC50 = 7.2-29.4 muM) 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 greater than or equal to 2a; 7a greater than or equal to 3), and the substituent such as Me at the oxime decreased inhibitory activity (6a greater than or equal to 6b; 7a greater than or equal to 7b). Among these derivatives, compound 6a showed the most potent activity with IC50 values of 6.5-11.6 muM for the inhibition of mast cell degranulation and neutrophil degranulation. (C) 2003 Elsevier Ltd. All rights reserved.