Dioxo-triazines as a novel series of cathepsin K inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1488-1490

  Rankovic, Zoran ^a   Cai, Jiaqiang ^a   Fradera, Xavier ^a   Dempster, Maureen ^a   Mistry, Ashvin ^a   Mitchell, Ann ^a   Long, Clive ^a   Hamilton, Emma ^a   King, Angela ^a   Boucharens, Sylviane ^a   Jamieson, Craig ^a   Gillespie, Jonathan ^a   Cumming, Iain ^a   Uitdehaag, Joost ^a   Zeeland, Mario van ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Cathepsin K; Cysteine protease; Osteoporosis

Indexed keywords

6 CYANO 2 (3' TRIFLUOROMETHYLPHENYL) 3,5 DIOXO 1,2,4 TRIAZINE; CATHEPSIN B; CATHEPSIN K INHIBITOR; CATHEPSIN L; CATHEPSIN S; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STABILITY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; IC 50; STRUCTURE ACTIVITY RELATION;

BINDING SITES; CATALYTIC DOMAIN; CATHEPSIN K; CRYSTALLOGRAPHY, X-RAY; CYSTEINE PROTEINASE INHIBITORS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES; URACIL;

EID: 76649126713     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.116     Document Type: Article

References (17)

1. Bonnick S.L. Clin. Cornerstone 8 (2006) 28
2. Rosen C.J., and Klibanski A. Am. J. Med. 122 (2009) 409
3. Troen B.R. Drug News Perspect. 17 (2004) 19
4. Hou W.S., Bromme D., Zhao Y., Mehler E., Dushey C., Weinstein H., Miranda C.S., Fraga C., Greig F., Carey J., Rimoin D.L., Desnick R.J., and Gelb B.D. J. Clin. Invest. 103 (1999) 731
5. Berti P.J., and Storer A.C. J. Mol. Biol. 246 (1995) 273
6. Cai J., Jamieson C., Moir J., and Rankovic Z. Exp. Opin. Ther. Pat. 15 (2005) 33
7. Deal C. Curr. Opin. Rheum. 21 (2009) 380
8. Grabowska U.B., Chambers T.J., and Shiroo M. Curr. Opin. Drug Discovery Dev. 8 (2005) 619
9. Lark M.W., Stroup G.B., James I.E., Dodds R.A., Hwang S.M., Blake S.M., Lechowska B.A., Hoffman S.J., Smith B.R., Kapadia R., Liang X., Erhard K., Ru Y., Dong X., Marquis R.W., Veber D., and Gowen M. Bone 30 (2002) 746
10. Kumar S., Dare L., Vasko-Moser J.A., James I.E., Blake S.M., Rickard D.J., Hwang S.-M., Tomaszek T., Yamashita D.S., Marquis R.W., Oh H., Jeong J.U., Veber D.F., Gowen M., Lark M.W., and Stroup G. Bone 40 (2007) 12
11. Stroup G.B., Lark M.W., Veber D.F., Bhattacharyya A., Blake S., Dare L., Erhard K.F., Hoffman S.J., James I.E., Marquis R.W., Ru Y., Vasko-Moser J.A., Smith B.R., Tomaszek T., and Gowen M. Bone Min. Res. 16 (2001) 1739
12. Adami S., Supronik J., Hala T., Brown J.P., Garnero P., Haemmerle S., Ortmann C.E., Bouisset F., and Trechsel U. J. Bone Min. Res. 21 (2006) S24
13. Stoch S.A., Zajic S., Stone J., Miller D.L., Van Dyck K., Gutierrez M.J., De Decker M., Liu L., Liu Q., Scott B.B., Panebianco D., Jin B., Duong L.T., Gottesdiener K., and Wagner J.A. Clin. Pharmacol. Ther. 86 (2009) 175
14. Subsequently, two research groups disclosed in the literature structurally related cathepsin K inhibitors:. Altmann E., Cowan-Jacob S.W., and Missbach M. J. Med. Chem. 47 (2004) 5833
15. Morley A.D., Kenny P.W., Burton B., Heald R.A., MacFaul P.A., Mullett J., Page K., Porres S.S., Ribeiro L.R., Smith P., Ward S., and Wilkinson T.J. Bioorg. Med. Chem. Lett. 19 (2009) 1658
16. Cooper C.B., McFarland J.W., Blair K.T., Fontaine E.H., Jones C.S., and Muzzi M.L. Bioorg. Med. Chem. Lett. 4 (1994) 835
17. 1Br, KI, DMSO, 70 °C, 1 h.