title: 2-Cyano-pyrimidines: a new chemotype for inhibitors of the cysteine protease cathepsin K.
abstract: Starting from the purine lead structure 1, a new series of cathepsin K inhibitors based on a pyrimidine scaffold have been explored. Investigations of P3 and P2 substituents based on molecular modeling suggestions resulted in potent cathepsin K inhibitors with an improved selectivity profile over other cathepsins.
authors.affiliation: Novartis Institutes of BioMedical Research, CH-4002 Basel, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Altmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Aichholz
authors.forename: Claudia
authors.initials: C
authors.lastname: Betschart
authors.forename: Thomas
authors.initials: T
authors.lastname: Buhl
authors.forename: Jonathan
authors.initials: J
authors.lastname: Green
authors.forename: Osamu
authors.initials: O
authors.lastname: Irie
authors.forename: Naoki
authors.initials: N
authors.lastname: Teno
authors.forename: René
authors.initials: R
authors.lastname: Lattmann
authors.forename: Marina
authors.initials: M
authors.lastname: Tintelnot-Blomley
authors.forename: Martin
authors.initials: M
authors.lastname: Missbach
mesh_terms: D000818:Animals; D001665:Binding Sites; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D009570:Nitriles; D011480:Protease Inhibitors; D011743:Pyrimidines; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056657:Cathepsin K; C534133:Ctsk protein, rat