Discovery of indeno[1,2-c]quinoline derivatives as inhibitors of osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL)

  • J Med Chem. 2011 Apr 28;54(8):3103-7. doi: 10.1021/jm1016494.
Chih-Hua Tseng  1 ,  Ru-Wei Lin ,  Yeh-Long Chen ,  Gwo-Jaw Wang ,  Mei-Ling Ho ,  Cherng-Chyi Tzeng
Affiliations
  • 1. Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City, Taiwan. [email protected]
PMID: 21456521 DOI: 10.1021/jm1016494
Abstract

Certain indeno[1,2-c]quinolines were synthesized and evaluated for antiosteoclastogenic activities. Among them, 6,9-dimethoxy-11H-indeno[1,2-c]quinolin-11-one (8a) and 9-methoxy-6-(methylthio)-11H-indeno[1,2-c]quinolin-11-one (16a) inhibited RANKL-induced osteoclast formation in Raw 264.7 cells with an IC(50) of 2.00 and 2.58 μM, respectively. Compound 8a was only weakly active in the inhibition of the RANKL-induced NFAT activation, while 16a was inactive. These results indicated that the antiosteoclastogenic effect of 8a is only partly related while 16a is not related to the suppression of NFAT.