Synthesis and anti-inflammatory activity of 2-oxo-2H-chromenyl and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates

Abstract

Cycloaddition reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehydes (3a-g) and 4-chloro-2H-chromene-3-carbaldehydes (7a-h) with activated alkynes (4a-b) provided the 2-oxo-2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (5a-n) and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (8a-p). All the prepared compounds were screened for anti-inflammatory activity. In vitro anti-inflammatory activity data demonstrated that the compounds 5g, 5i, 5k-l and 8f are effective among the tested compounds against TNF-α (1.108 ± 0.002, 0.423 ± 0.022, 0.047 ± 0.001, 0.070 ± 0.002 and 0.142 ± 0.001 µM) in comparison with standard compound Prednisolone (0.033 ± 0.002 µM). Based on in vitro results, three compounds (5i, 5k and 8f) have been selected for in vivo experiments and these compounds are identified as better compounds with respect to anti-inflammatory activity in LPS induced mice model. Compound 5i was identified as potent and showed significant reduction in TNF-α and IL-6.

Keywords: 2H-Chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates; 4-Chloro-2-oxo-2H-chromene-3-carbaldehydes; 4-Chloro-2H-chromene-3-carbaldehydes; Activated alkynes; Cycloaddition reaction.