Metastatic bone tumors occur at particularly high rates in cancers of the breast, prostate, and lung, accounting more than 70% of all patients. Treatment of skeletal metastasis and development of new specific “blockers” of bone resorption are relevant. Pyrimidine-fused betulinic acid may be considered as promising compounds for the design of novel inhibitors of osteoclast differentiation and bone resorption. Jun Xu et coworkers synthesized over 20 heterocyclic ring-fused betulinic acid derivatives and evaluated their inhibition on RANKL-induced osteoclast formation in preosteoclast RAW264.7 cells (Xu et al., 2012). Some compounds exhibited potent inhibitory activity on RANKL-induced osteoclast formation by TRAP assay.