New chemotypes for cathepsin K inhibitors.
Cyano pyrimidine acetylene and cyano pyrimidine t-amine, which belong to a new chemical class, were prepared and tested for inhibitory activities against cathepsin K and the highly homologous cathepsins L and S. The use of novel chemotypes in the development of cathepsin K inhibitors has been demonstrated by derivatives of compounds 1 and 8.
Teno
Naoki
N
Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki 300-2611, Japan. naoki.teno@novartis.com
Irie
Osamu
O
Miyake
Takahiro
T
Gohda
Keigo
K
Horiuchi
Miyuki
M
Tada
Sachiyo
S
Nonomura
Kazuhiko
K
Kometani
Motohiko
M
Iwasaki
Genji
G
Betschart
Claudia
C
D001665:Binding Sites; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K