Author/Authors :
Tsuyoshi Shinozuka، نويسنده , , Kousei Shimada، نويسنده , , Satoshi Matsui، نويسنده , , Takahiro Yamane، نويسنده , , Mayumi Ama، نويسنده , , Takeshi Fukuda، نويسنده , , Motohiko Taki، نويسنده , , Yuko Takeda، نويسنده , , Eri Otsuka، نويسنده , , Michiko Yamato، نويسنده , , Shinichi Mochizuki، نويسنده , , Keiko Ohhata، نويسنده , , Satoru Naito، نويسنده ,
Abstract :
A novel series of cathepsin K inhibitors derived from Novartis compound I is described. Optimization of the P1, P3, and P1′ units led to the identification of 4-aminophenoxyacetic acid 24b with an IC50 value of 4.8 nM, which possessed an excellent selectivity over other human cathepsins and good pharmacokinetic (PK) properties. Oral administration of compound 24b to ovariectomized (OVX) rats showed a trend toward an improvement of bone mineral density (BMD) in the femur bone.
Keywords :
cathepsin K , OVX rat assay , SAR study , Inhibitor
