Formononetin Derivative for Osteoporosis by Simultaneous Regulating Osteoblast and Osteoclast.

Seven new formononetin derivatives ( 1 - 7 ) were designed and prepared from formononetin (phase II phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4 H ,8 H -chromeno[8,7- e ][1,3]oxazin-4-one ( 2 ) and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4 H ,8 H -chromeno[8,7- e ][1,3]oxazin-4-one ( 7 ) promoted significant osteoblast formation by modulating the BMP/Smad pathway. Compound 7 exhibited potent antiosteoclastogenesis activity in RANKL-induced RAW264.7 cells and ovariectomy (OVX)-induced osteoporosis in mice by regulation of the RANK/RANKL/OPG pathway. Compound 7 regulated osteoblast and osteoclast simultaneously and showed better effect than the well-known drug ipriflavone in vivo , suggesting 7 as a patented antiosteoporosis candidate.