2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 15, 2010, Pages 4447-4450

  Cai, Jiaqiang ^a   Bennett, D Jonathan ^a   Rankovic, Zoran ^a   Dempster, Maureen ^a   Fradera, Xavier ^a   Gillespie, Jonathan ^a   Cumming, Iain ^a   Finlay, William ^a   Baugh, Mark ^a   Boucharens, Sylviane ^a   Bruin, John ^a   Cameron, Kenneth S ^a   Hamilton, William ^a   Kerr, Jennifer ^a   Kinghorn, Emma ^a   McGarry, George ^a   Robinson, John ^a   Scullion, Paul ^a   Uitdehaag, Joost C M ^a   Van Zeeland, Mario ^a   Potin, Dominique ^b   Saniere, Laurent ^b   Fouquet, Andre ^b   Chevallier, Francois ^b   Deronzier, Hortense ^b   Dorleans, Cecile ^b   Nicolai, Eric ^b   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b CEREP   (France)

Author keywords

Cathepsin S; Lysosomotropism; Purine 6 carbonitrile; Transition state

Indexed keywords

2 PHENYL 9H PURINE 6 CARBONITRILE DERIVATIVE; CATHEPSIN S INHIBITOR; CYANIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS;

CATALYTIC DOMAIN; CATHEPSIN K; CATHEPSINS; CELL LINE; COMPUTER SIMULATION; HUMANS; NITRILES; PROTEASE INHIBITORS; PURINES; PYRIMIDINES;

EID: 77955426595     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.06.049     Document Type: Article

References (21)

1. S. Gupta, R.K. Singh, S. Dastidar, and A. Ray Expert Opin. Ther. Targets 12 2008 291
2. V. Leroy, and S. Thurairatnam Expert Opin. Ther. Patents 14 2004 301
3. J. Cai, C. Jamieson, J. Moir, and Z. Rankovic Expert Opin. Ther. Patents 15 2005 33
4. D. Bromme, and F. Lecaille Expert Opin. Invest. Drugs 18 2009 585
5. A.K. Clark, P.K. Yip, J. Grist, C. Gentry, A.A. Staniland, F. Marchand, M. Dehvari, G. Wotherspoon, J. Winter, J. Ullah, S. Bevan, and M. Malcangio Proc. Natl. Acad. Sci. U.S.A. 104 2007 10655
6. Z. Rankovic, J. Cai, X. Fradera, M. Dempster, A. Mistry, A. Mitchell, C. Long, E. Hamilton, A. King, S. Boucharens, C. Jamieson, J. Gillespie, I. Cumming, J. Uitdehaag, and M. Zeeland Bioorg. Med. Chem. Lett. 20 2010 1488
7. Z. Rankovic, J. Cai, J. Kerr, X. Fradera, J. Robinson, A. Mistry, E. Hamilton, G. McGarry, F. Andrews, W. Caulfield, I. Cumming, M. Dempster, J. Waller, P. Scullion, I. Martin, A. Mitchell, C. Long, M. Baugh, P. Westwood, E. Kinghorn, J. Bruin, W. Hamilton, J. Uitdehaag, M. Zeeland, D. Potin, L. Saniere, A. Fouquet, F. Chevallier, H. Deronzier, C. Dorleans, and E. Nicolai Bioorg. Med. Chem. Lett. 20 2010 1524
8. E. Altmann, S.W. Cowan-Jacob, and M. Missbach J. Med. Chem. 47 2004 5833
9. O. Irie, T. Ehara, A. Iwasaki, F. Yokokawa, J. Sakaki, H. Hirao, T. Kanazawa, N. Teno, M. Horiuchi, I. Umemura, H. Gunji, K. Masuya, Y. Hitomi, G. Iwasaki, K. Nonomura, K. Tanabe, H. Fukaya, T. Kosaka, C.R. Snell, and A. Hallet Bioorg. Med. Chem. Lett. 18 2008 3959
10. O. Irie, F. Yokokawa, T. Ehara, A. Iwasaki, Y. Iwaki, Y. Hitomi, K. Konishi, M. Kishida, A. Toyao, K. Masuya, H. Gunji, J. Sakaki, G. Iwasaki, H. Hirao, T. Kanazawa, K. Tanabe, T. Kosaka, T.W. Hart, and A. Hallet Bioorg. Med. Chem. Lett. 18 2008 4642
11. O. Irie, T. Kosaka, M. Kishida, J. Sakaki, K. Masuya, K. Konishi, F. Yokokawa, T. Ehara, A. Iwasaki, Y. Iwaki, Y. Hitomi, A. Toyao, H. Gunji, N. Teno, G. Iwasaki, H. Hirao, T. Kanazawa, K. Tanabe, P. Hiestand, M. Malcangio, A.J. Fox, S.J. Bevan, M. Yaqoob, A.J. Culshaw, T.W. Hart, and A. Hallet Bioorg. Med. Chem. Lett. 18 2008 5280
12. O. Irie, T. Kosaka, T. Ehara, F. Yokokawa, T. Kanazawa, H. Hirao, A. Iwasaki, J. Sakaki, N. Teno, Y. Hitomi, G. Iwasaki, H. Fukaya, K. Nonomura, K. Tanabe, S. Koizumi, N. Uchiyama, S.J. Bevan, M. Malcangio, C. Gentry, A.J. Fox, M. Yaqoob, A.J. Culshaw, and A. Hallet J. Med. Chem. 51 2008 5502
13. E. Altmann, R. Aichholz, C. Betschart, T. Buhl, J. Green, O. Irie, N. Teno, R. Lattmann, M. Tintelnot-Blomley, and M. Missbach J. Med. Chem. 50 2007 591
14. N. Teno, T. Miyake, T. Ehara, O. Irie, J. Sakaki, O. Ohmori, H. Gunji, N. Matsuura, K. Masuya, Y. Hitomi, K. Nonomura, M. Horiuchi, K. Gohda, A. Iwasaki, I. Umemura, S. Tada, M. Kometani, G. Iwasaki, S.W. Cowan-Jacob, M. Missbach, R. Lattmann, and C. Betschart Bioorg. Med. Chem. Lett. 17 2007 6096
15. N. Teno, K. Masuya, T. Ehara, T. Kosaka, T. Miyake, O. Irie, Y. Hitomi, N. Matsuura, I. Umemura, G. Iwasaki, H. Fukaya, K. Toriyama, N. Uchiyama, I. Sugiyama, and M. Kometani J. Med. Chem. 51 2008 5459
16. N. Teno, O. Irie, T. Miyake, K. Gohda, M. Horiuchi, S. Tada, K. Nonomura, M. Kometani, G. Iwasaki, and C. Betschart Bioorg. Med. Chem. Lett. 18 2008 2599
17. A.D. Morley, P.W. Kenny, B. Burton, R.A. Heald, P.A. MacFaul, J. Mullett, K. Page, S.S. Porres, L.R. Riberio, P. Smith, S. Ward, and T.J. Wilkinson Bioorg. Med. Chem. Lett. 19 2009 1658
18. J.Y. Gauthier, W.C. Black, I. Courchesne, W. Cromlish, S. Desmarais, R. Houle, S. Lamontagne, C.S. Li, F. Masse, D.J. Mckay, M. Ouellet, J. Robichaud, J.-F. Truchon, V.-L. Truong, Q. Wang, and M.D. Percival Bioorg. Med. Chem. Lett. 17 2007 4929
19. J.-P. Falgueyret, S. Desmarais, R. Oballa, W.C. Black, W. Cromlish, K. Khougaz, S. Lamontagne, F. Masse, D. Riendeau, S. Toulmond, and M.D. Percival J. Med. Chem. 48 2005 7535
20. A. MacIntyre, and D.J. Cutler Biopharm. Drug Dispos. 9 1988 513
21. 2O at 20 °C at pD 7.5. Structure of the compound measured is shown below which is synthesized according to Scheme 2.