title: Novel scaffold for cathepsin K inhibitors.
abstract: 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.
authors.affiliation: Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki, Japan. naoki.teno@novartis.com
authors.forename: Naoki
authors.initials: N
authors.lastname: Teno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyake
authors.forename: Takeru
authors.initials: T
authors.lastname: Ehara
authors.forename: Osamu
authors.initials: O
authors.lastname: Irie
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Hiroki
authors.initials: H
authors.lastname: Gunji
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsuura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masuya
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nonomura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Keigo
authors.initials: K
authors.lastname: Gohda
authors.forename: Atsuko
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Umemura
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Tada
authors.forename: Motohiko
authors.initials: M
authors.lastname: Kometani
authors.forename: Genji
authors.initials: G
authors.lastname: Iwasaki
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Cowan-Jacob
authors.forename: Martin
authors.initials: M
authors.lastname: Missbach
authors.forename: René
authors.initials: R
authors.lastname: Lattmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Betschart
mesh_terms: 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
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D011994:Recombinant Proteins; C527741:pyrrolopyrimidine; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K