Novel scaffold for cathepsin K inhibitors.
Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20.
Teno
Naoki
N
Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki, Japan. naoki.teno@novartis.com
Miyake
Takahiro
T
Ehara
Takeru
T
Irie
Osamu
O
Sakaki
Junichi
J
Ohmori
Osamu
O
Gunji
Hiroki
H
Matsuura
Naoko
N
Masuya
Keiichi
K
Hitomi
Yuko
Y
Nonomura
Kazuhiko
K
Horiuchi
Miyuki
M
Gohda
Keigo
K
Iwasaki
Atsuko
A
Umemura
Ichiro
I
Tada
Sachiyo
S
Kometani
Motohiko
M
Iwasaki
Genji
G
Cowan-Jacob
Sandra W
SW
Missbach
Martin
M
Lattmann
René
R
Betschart
Claudia
C
D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D011743:Pyrimidines; D011758:Pyrroles; D011994:Recombinant Proteins; C527741:pyrrolopyrimidine; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K