title: Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis.
abstract: As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclast's early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.
authors.forename: Ting-Hao
authors.initials: TH
authors.lastname: Kuo
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Lin
authors.affiliation: §Department of Orthopedics, College of Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Rong-Sen
authors.initials: RS
authors.lastname: Yang
authors.affiliation: ∥Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 404, Taiwan.
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
authors.affiliation: ⊥Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, 404, Taiwan.|#School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Hung
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010052:Ovariectomy; D011720:Pyrazoles / Q000737:chemistry* / Q000627:therapeutic use*; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000276:immunology; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D016328:NF-kappa B; D011720:Pyrazoles; D053245:RANK Ligand