Novel Pyrazole Derivatives for Treating Osteoporosis

Abstract

Osteoporosis is known as an age-related disease that result from an imbalance between the generation and decomposition of the bone matrix It is caused by either the degeneration of osteoblasts leading to weaker bone forming activity or the promotion of osteoclasts increasing bone resorption activity To treat osteoporosis several drugs are available now However there are still some drawbacks of the drugs such as many side effects and high cost According to the situation we would like to research and synthesize new compounds to treat osteoporosis 3-(5’-Hydroxymethyl-2’-furyl)-1-benzyl indazole (YC-1) (1) is a pyrazole derivative that has been demonstrated with many potent biological and pathological activities YC-1 was also exhibited anti-osteoporosis effects through promoting cGMP by activating sGC and then reducing osteoclast activity and inducing osteoblast activity According to the above-mentioned feature many YC-1 derivatives had been synthesized with different side chains to study structure-activity relationship Among them 2-(dimethylamino)ethyl group showed obvious inhibition of osteoclast both in vitro and in vivo However previous researches did not include variable side chains; therefore there is still much room for new YC-1 derivatives to figure out structure-activity relationship (SAR) of YC-1 derivatives In this study we would like to synthesize novel YC-1 derivatives that are effective in treating osteoporosis without many side effects and high cost Based on the previous research we modified the side chains on indazole such as replacement of the furan with pyridine and thiophene On the other hand we also transformed the 1-benzyl group with 3-fluorobenzyl group Then we characterized the compound structures with 1H and 13C NMR to check that three target compounds were synthesized successfully

Date of Award	2018 Sept 3
Original language	English
Supervisor	Yu-Hung Chen (Supervisor)