4-Aminophenoxyacetic acids as a novel class of reversible cathepsin K inhibitors.
We have designed and synthesized a novel series of 3-biphenylamino acid amides as cathepsin K inhibitors based on compound I. In these inhibitors, we have discovered 4-aminophenoxyacetic acids 43 and 47 with good IC(50) values, although lipophilic groups are favorable for the hydrophobic S1' pocket.
Shinozuka
Tsuyoshi
T
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. sinozu@sankyo.co.jp
Shimada
Kousei
K
Matsui
Satoshi
S
Yamane
Takahiro
T
Ama
Mayumi
M
Fukuda
Takeshi
T
Taki
Motohiko
M
Naito
Satoru
S
D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D010642:Phenoxyacetates / Q000138:chemical synthesis* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D010642:Phenoxyacetates; D011994:Recombinant Proteins; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K