Design and synthesis of tetracyclic nonpeptidic biaryl nitrile inhibitors of cathepsin K

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 16, 2006, Pages 4296-4299

  Setti, Eduardo L ^a   Venkatraman, Shankar ^a   Palmer, James T ^a   Xie, Xiaoming ^a   Cheung, Harry ^a   Yu, Walter ^a   Wesolowski, Gregg ^b   Robichaud, Joel ^b  

^a CELERA   (United States)

^b MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

Cathepsin K inhibitors; Nonpeptidic biaryl nitriles

Indexed keywords

CATHEPSIN K; CATHEPSIN K INHIBITOR; CYSTEINE PROTEINASE; CYSTEINE PROTEINASE INHIBITOR; NITRILE;

ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG DETERMINATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; NONHUMAN; OSTEOPOROSIS; RAT; STRUCTURE ACTIVITY RELATION;

AREA UNDER CURVE; CATHEPSIN B; CATHEPSINS; CHEMISTRY, PHARMACEUTICAL; CYSTEINE ENDOPEPTIDASES; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; MODELS, MOLECULAR; NITRILES; OSTEOPOROSIS;

EID: 33745684879     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.05.061     Document Type: Article

References (9)

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2. Robichaud J., Oballa R., Prasit P., Falgueyret J.-P., Percival M.D., Wesolowski G., Rodan S.B., Kimmel D., Johnson C., Bryant C., Venkatraman S., Setti E., Mendonca R., and Palmer J.T. J. Med. Chem. 46 (2003) 3709
3. 50 of compound 1 in Ref. 2 is 3 nM.
4. Falgueyret J.P., Oballa R.M., Okamoto O., Wesolowski G., Aubin Y., Rydzewski R.M., Prasit P., Riendeau D., Rodan S.B., and Percival M.D. J. Med. Chem. 44 (2001) 94
5. Palmer J.T., Bryant C., Wang D.-X., Davis D.E., Setti E.L., Rydzewski R.M., Venkatraman S., Tian Z.-Q., Burrill L.C., Mendonca R.V., Springman E., McCarter J., Chung T., Cheung H., Janc J.W., McGrath M., Somoza J., Enriquez P., Yu Z.W., Strickley R.M., Liu L., Venuti M.C., Percival M.C., Falgueyret J.-P., Prasit P., Oballa R., Riendeau D., Young R.N., Wesolowski G., Rodan S.V., Johnson C., Kimmel D.B., and Rodan G. J. Med. Chem. 48 (2005) 7520
6. Setti E.L., Davis D., Janc J., Jeffery D.A., Cheung H., and Yu W. Bioorg. Med. Chem. Lett. 15 (2005) 1529
7. 158.
8. Same enzyme assay conditions as described in Ref. 5.
9. The presence of a basic nitrogen at the distal position of the molecule was shown to be essential for potency and selectivity in other series. See Refs. 4-6.