Abstract
A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents.
Original language | English |
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Pages (from-to) | 4522-4532 |
Number of pages | 11 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 23 |
Issue number | 15 |
DOIs | |
Publication status | Published - Jul 23 2015 |
Keywords
- NDMC101
- Osteoclastogenesis
- Pit formation assay
- RANKL
- TRAP-staining assay
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Fingerprint Dive into the research topics of 'Novel inhibitors of RANKL-induced osteoclastogenesis: Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones'. Together they form a unique fingerprint.
Datasets
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CCDC 1417633: Experimental Crystal Structure Determination
Lee, C. (Contributor), Liu, F. (Contributor), Chen, C. (Contributor), Chen, T. (Contributor), Liu, F. (Contributor), Ali, A. A. A. (Contributor), Chang, D. (Contributor) & Huang, H. (Contributor), Unknown Publisher, Jul 23 2015
DOI: 10.5517/cc1jl53d, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/cc1jl53d&sid=DataCite
Dataset