Dipeptide nitrile inhibitors of cathepsin K

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 9, 2006, Pages 2549-2554

  Altmann, Eva ^a   Aichholz, Reiner ^a   Betschart, Claudia ^a   Buhl, Thomas ^a   Green, Jonathan ^a   Lattmann, René ^a   Missbach, Martin ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CATHEPSIN K; CATHEPSIN K INHIBITOR; DIPEPTIDE DERIVATIVE; NITRILE;

ARTICLE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; IC 50; NONHUMAN;

ANIMALS; CATHEPSINS; DIPEPTIDES; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; MICROSOMES, LIVER; MOLECULAR STRUCTURE; NITRILES; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33644990101     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.01.104     Document Type: Article

References (16)

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12. 50 values were also determined against cathepsin B and found to be >100 nM (selectivity ratio CatK/CatB ≫100).
13. 2O/0.1% HCOOH and the samples were submitted for HPLC/MS-MS analysis.
14. 2O/0.1% HCOOH and the samples were submitted for HPLC/MS-MS analysis.
15. No specific degradation products could be detected under our experimental conditions.
16. -1. Blood samples were collected from the femoral artery for 24 h after iv and after oral dosing. Iv and po administration was carried out in the same animals with a 48 h washout period between administrations. After acetonitrile precipitation of plasma samples, parent drug concentrations in extracts were measured using a specific HPLC/MS method.