2-Cyano-pyrimidines: A New Chemotype for Inhibitors of the Cysteine Protease Cathepsin K

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 ot...

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Veröffentlicht in:	Journal of medicinal chemistry 2007-02, Vol.50 (4), p.591-594
Hauptverfasser:	Altmann, Eva, Aichholz, Reiner, Betschart, Claudia, Buhl, Thomas, Green, Jonathan, Irie, Osamu, Teno, Naoki, Lattmann, René, Tintelnot-Blomley, Marina, Missbach, Martin
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Binding Sites Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cathepsin K Cathepsins - antagonists & inhibitors Cathepsins - chemistry Crystallography, X-Ray Cysteine Endopeptidases - chemistry Medical sciences Models, Molecular Nitriles - chemical synthesis Nitriles - chemistry Nitriles - pharmacokinetics Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacokinetics Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacokinetics Rats Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm0613525