Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K.
Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.
Altmann
Eva
E
Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. eva.altmann@pharma.novartis.com
Cowan-Jacob
Sandra W
SW
Missbach
Martin
M
D000818:Animals; D001665:Binding Sites; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D011687:Purines; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat