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Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis
- Source :
- Journal of Medicinal Chemistry. 58:4954-4963
- Publication Year :
- 2015
- Publisher :
- American Chemical Society (ACS), 2015.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Ovariectomy
Osteoporosis
Osteoclasts
Pyrazole
Inhibitory postsynaptic potential
Bone resorption
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
Bone Density
In vivo
Osteoclast
Internal medicine
Drug Discovery
medicine
Animals
Humans
Bone Resorption
Cells, Cultured
Tibia
RANK Ligand
NF-kappa B
Cell Differentiation
medicine.disease
In vitro
Endocrinology
medicine.anatomical_structure
chemistry
Ovariectomized rat
Pyrazoles
Molecular Medicine
Female
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....a2246f9c40b8922630af30b5d6707978