A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin(1),6,8-dimethylgenistein(2) and their analogues(3-8) is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill’s protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide(NO) in lipopolysaccharide(LPS)-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_(50) values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control(N-monomethyl-L-arginine,L-NMMA). A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin (1), 6,8-dimethylgenistein (2) and their analogues (3-8) is established for the first time. The synthesis is realized in 7-8 steps in Overall yields of 16% -24% from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction, Friedel-Crafts acylation, Gammill’s protocol and Suzuki coupling as the pivotal transformations .Next, these compounds evaluated their inhibitory potency on the production of nitric oxide (NO) in lipopolysaccharide (LPS) -activated RAW-264.7 cells as an indicator of anti-inflammatory activity. The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_ (50) values were found in the range of 10.17-33.88 μmol / L.Of note, compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control (N-monomethyl-L-arginine, L-NMMA).