Certain indeno[l,2-c]quinolines were synthesized and evaluated for anti-osteoclastogenic activities. Among them, 6,9-dimethoxy-11H-indeno[l,2-c]- quinolin-11 -one (8a) and 9-methoxy-6-(methylthio)-11H-indeno[ 1,2-c] quinolin-11 -one (16a) inhibited RANKL-induced osteoclast formation in Raw 264.7 cells with an IC50 of 2.00 and 2.58 M respectively. Compound 8a was only weekly active in the inhibition of the RANKL-induced NFAT activation while 16a was inactive. These results indicated that the anti-osteoclastogenic effect of 8a is only partly related while 16a is not related to the suppression of NFAT.