Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L

Journal of Medicinal Chemistry

Volumn 44, Issue 1, 2001, Pages 94-104

  Falgueyret, J P ^a   Oballa, R M ^a   Okamoto, O ^a   Wesolowski, G ^b   Aubin, Y ^a   Rydzewski, R M ^c   Prasit, P ^a   Riendeau, D ^a   Rodan, S B ^b   Percival, M D ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

^b MERCK RESEARCH LABORATORIES   (United States)

^c Axys Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 CYANOPYRROLIDINYL; AZETIDINE DERIVATIVE; CATHEPSIN K; CATHEPSIN L; COLLAGEN; CYANAMIDE; CYSTEINE; ENZYME INHIBITOR; GLUTATHIONE; N (1 CYANO 3 PYRROLIDINYL)BENZENESULFONAMIDE; N [N (3 CARBOXYOXIRANE 2 CARBONYL)LEUCYL]AGMATINE; PAPAIN; PROTEINASE; PYRROLIDINE DERIVATIVE; QUINOLINE; UNCLASSIFIED DRUG;

ARTICLE; CATTLE; CHEMICAL REACTION; COLLAGEN DEGRADATION; COVALENT BOND; DRUG POTENCY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; IN VITRO STUDY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; OSTEOCLAST; OSTEOLYSIS; PROTEIN MODIFICATION; RABBIT;

ANIMALS; BONE AND BONES; BONE RESORPTION; CATALYTIC DOMAIN; CATHEPSINS; CATTLE; COLLAGEN; CYSTEINE; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; ENDOPEPTIDASES; GLUTATHIONE; HUMANS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; NITRILES; OSTEOCLASTS; PYRROLIDINES; RABBITS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 0035804301     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0003440     Document Type: Article

References (23)

1. Lysosomal cysteine proteases: More than scavengers
2. Catalytic mechanism in papain family of cysteine peptidases
3. Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain
4. Increased cathepsin B activity in multiple sclerosis brain
5. Demonstration of cathepsins B, H and L in xenografts of normal and Duchenne-muscular-dystrophy muscles transplanted into nude mice
6. The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma
7. Cathepsin S activity regulates antigen presentation and immunity
8. Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2
9. Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas
10. Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution
11. In vivo and in vitro evidence for the involvement of cysteine proteinases in bone resorption
12. Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases
13. Cysteine proteinases and matrix metalloproteinases play distinct roles in the subosteoclastic resorption zone
14. Cathepsin K and the design of inhibitors of cathepsin K
15. The behavior and significance of slow-binding enzyme inhibitors
16. Avidin is a slow-binding inhibitor of pyruvate carboxylase
17. Reversible covalent binding of peptide nitriles to papain
18. Engineering nitrile hydratase activity into a cysteine protease by a single mutation
19. Benzoylamidoacetonitrile is bound as a thioimidate in the active site of papain
20. Reversible covalent inhibition of papain by a peptide nitrile. 13C NMR evidence for a thioimidate ester adduct
21. Synthesis and muscarinic activities of 1,2,4-thiadiazoles
22. Synthesis of novel four-membered ring amino acids as modulatorrs of the n-methyl-d-aspartate(NMDA) receptor complex
23. Transition-state structural features for the association of metalloproteases with phosphorus-containing inhibitors