title: Effect of cathepsin K inhibitors on bone resorption.
abstract: On the basis of the pyrrolopyrimidine core structure that was previously discovered, cathepsin K inhibitors having a spiro amine at the P3 have been explored to enhance the target, bone marrow, tissue distribution. Several spiro structures were identified with improved distribution toward bone marrow. The representative inhibitor 7 of this series revealed in vivo reduction in C-terminal telopeptide of type I collagen in rats and monkeys.
authors.affiliation: Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki 300-2611, Japan. naoki.teno@novartis.com
authors.forename: Naoki
authors.initials: N
authors.lastname: Teno
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masuya
authors.forename: Takeru
authors.initials: T
authors.lastname: Ehara
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kosaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyake
authors.forename: Osamu
authors.initials: O
authors.lastname: Irie
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsuura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Umemura
authors.forename: Genji
authors.initials: G
authors.lastname: Iwasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fukaya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toriyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Uchiyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nonomura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sugiyama
authors.forename: Motohiko
authors.initials: M
authors.lastname: Kometani
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001862:Bone Resorption / Q000188:drug therapy*; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D024042:Collagen Type I / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics*; D000882:Haplorhini; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013141:Spiro Compounds; D014018:Tissue Distribution
chemical_list: D024042:Collagen Type I; D015853:Cysteine Proteinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013141:Spiro Compounds; C527741:pyrrolopyrimidine; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat