Discovery of selective and nonpeptidic cathepsin S inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 14, 2008, Pages 3959-3962

  Irie, Osamu ^a   Ehara, Takeru ^a   Iwasaki, Atsuko ^a   Yokokawa, Fumiaki ^a   Sakaki, Junichi ^a   Hirao, Hajime ^a   Kanazawa, Takanori ^a   Teno, Naoki ^a   Horiuchi, Miyuki ^a   Umemura, Ichiro ^a   Gunji, Hiroki ^a   Masuya, Keiichi ^a   Hitomi, Yuko ^a   Iwasaki, Genji ^a   Nonomura, Kazuhiko ^a   Tanabe, Keiko ^a   Fukaya, Hiroaki ^a   Kosaka, Takatoshi ^a   Snell, Christopher R ^b   Hallett, Allan ^b  

^a Novartis Institutes for BioMedical Research   (Japan)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

Cathepsin S inhibitor; Cysteine protease; Nitrile; Nonpeptidic; Pyrrolopyrimidine

Indexed keywords

CATHEPSIN K; CATHEPSIN K INHIBITOR; CATHEPSIN L; CATHEPSIN S; CATHEPSIN S INHIBITOR; CYSTEINE PROTEINASE; PYRROLOPYRIMIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROPHOBICITY; IC 50; MALE; NONHUMAN; RAT; SPLEEN CELL; STRUCTURE ACTIVITY RELATION;

BIOLOGICAL AVAILABILITY; CATHEPSINS; CHEMISTRY, PHARMACEUTICAL; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 47149115085     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.06.009     Document Type: Article

References (22)

1. For a recent review of cathespin S, see:. Gupta S., Singh R.K., Dastidar S., and Ray A. Expert Opin. Ther. Targets 12 (2008) 291
2. Clark A.K., Yip P.K., Grist J., Gentry C., Staniland A.A., Marchand F., Dehvari M., Wotherspoon G., Winter J., Ullah J., Bevan S., and Malcangio M. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 10655
3. Barclay J., Clark A.K., Ganju P., Gentry C., Patel S., Wotherspoon G., Buxton F., Song C., Ullah J., Winter J., Fox A., Bevan S., and Malcangio M. Pain 130 (2007) 225
4. For recent reviews of cysteine proteases, see:. Vasiljeva O., Reinheckel T., Peters C., Turk D., Turk V., and Turk B. Curr. Pharm. Des. 13 (2007) 387
5. Palermo C., and Joyce J.A. Trends Pharmacol. Sci. 29 (2007) 22
6. Maryanoff B.E., and Costanzo M.J. Bioorg. Med. Chem. 16 (2008) 1562
7. Lutgens S.P.M., Cleutjens K.B.J.M., Daemen M.J.A.P., and Heeneman S. FASEB J. 21 (2007) 3029
8. For a recent review of cathespin S inhibitors, see:. Link J.O., and Zipfel S. Curr. Opin. Drug Discov. Dev. 9 (2006) 471
9. For a recent peptidic cathespin S inhibitors, see:. Gauthier J.Y., Black W.C., Courchesne I., Cromlish W., Desmarais S., Houle R., Lamontagne S., Li C.S., Massé F., McKay D.J., Ouellet M., Robichaud J., Truchon J.-F., Truong V.-L., Wang Q., and Percival M.D. Bioorg. Med. Chem. Lett. 17 (2007) 4929
10. Chatterjee A.K., Liu H., Tully D.C., Guo J., Epple R., Russo R., Williams J., Roberts M., Tuntland T., Chang J., Gordon P., Hollenbeck T., Tumanut C., Li J., and Harris J.L. Bioorg. Med. Chem. Lett. 17 (2007) 2899
11. Bekkali Y., Thomson D.S., Betageri R., Emmanuel M.J., Hao M.-H., Hickey E., Liu W., Patel U., Ward Y.D., Young E.R.R., Nelson R., Kukulka A., Brown M.L., Crane K., White D., Freeman D.M., Labadia M.E., Wildeson J., and Spero D.M. Bioorg. Med. Chem. Lett. 17 (2007) 2465
12. For a recent nonpeptidic cathespin S inhibitors, see:. Wei J., Pio B.A., Cai H., M eduna S.P., Sun S., Gu Y., Jiang W., Thurmond R.L., Karlsson L., and Edwards J.P. Bioorg. Med. Chem. Lett. 17 (2007) 5525
13. Inagaki H., Tsuruoka H., Hornsby M., Lesley S.A., Spraggon G., and Ellman J.A. J. Med. Chem. 50 (2007) 2693
14. Pauly T.A., Sulea T., Ammirati M., Sivaraman J., Danley D.E., Griffor M.C., Kamath A.V., Wang I.-K., Laird E.R., Seddon A.P., Menard R., Cygler M., and Rath V.L. Biochemistry 42 (2003) 3203
15. Teno N., Miyake T., Ehara T., Irie O., Sakaki J., Ohmori O., Gunji H., Matsuura N., Masuya K., Hitomi Y., Nonomura K., Horiuchi M., Gohda K., Iwasaki A., Umemura I., Tada S., Kometani M., Iwasaki G., Cowan-Jacob S.W., Missbach M., Lattmann R., and Betschart C. Bioorg. Med. Chem. Lett. 17 (2007) 6096
16. Chowdhury S.F., Sivaraman J., Wang J., Devanathan G., Lachance P., Qi H., Ménard R., Lefebvre J., Konishi Y., Cygler M., Sulea T., and Purisima E.O. J. Med. Chem. 45 (2002) 5321
17. Altmann E., Aichholz R., Betschart C., Buhl T., Green J., Irie O., Teno N., Lattmann R., Tintelnot-Blomley M., and Missbach M. J. Med. Chem. 50 (2007) 591
18. 1H NMR and MS. The experimental information is described in a patent application, see: Buxton, F. P.; Ehara, T.; Ganju, P.; Hallett, A.; Irie, O.; Iwasaki, A.; Kanazawa, T.; Masuya, K.; Nonomura, K.; Sakaki, J.; Snell, C. R.; Song, C.; Tanabe, K.; Teno, N; Umemura, I.; Yokokawa, F. WO 2004069656, 2004.
19. Preparation of 11c; A Sonogashira reaction of 7 with prop-2-ynylcyclohexane as an alkyne under the same condition as (b) followed by a cyclization condition (c) in Scheme 2, yielded 11c.
20. Riese R.J., Wolf P.R., Brömme D., Natkin L.R., Villadangos J.A., Ploegh H.L., and Chapman H.A. Immunity 4 (1996) 357
21. Manitpisitkul P., and White R.E. Drug Discovery Today 9 (2004) 652
22. Janser P., Neumann U., Miltz W., Feifel R., and Buhl T. Bioorg. Med. Chem. Lett. 16 (2006) 2632