Discovery of novel hydroxamates as highly potent tumor necrosis factor-α converting enzyme inhibitors. Part II: Optimization of the S3′ pocket

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 21, 2008, Pages 5809-5814

  Mazzola Jr , Robert D ^a   Zhu, Zhaoning ^a   Sinning, Lisa ^a   McKittrick, Brian ^a   Lavey, Brian ^a   Spitler, James ^a   Kozlowski, Joseph ^a   Neng Yang, Shih ^a   Zhou, Guowei ^a   Guo, Zhuyan ^a   Orth, Peter ^a   Madison, Vincent ^a   Sun, Jing ^a   Lundell, Daniel ^a   Niu, Xiaoda ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

MMP inhibitors; TACE inhibitors

Indexed keywords

ADAM 10 PROTEIN; ADAM PROTEIN; ETANERCEPT; GELATINASE A; HYDROXAMIC ACID DERIVATIVE; INFLIXIMAB; INTERSTITIAL COLLAGENASE; MATRILYSIN; MATRIX METALLOPROTEINASE 14; STROMELYSIN; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CELL STRAIN CACO 2; CONTROLLED STUDY; CROHN DISEASE; CYCLOPROPANATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG INDICATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; HUMAN; HUMAN CELL; HYDROGENATION; IC 50; NONHUMAN; PSORIASIS; RAT; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ADAM PROTEINS; ANIMALS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; DRUG DISCOVERY; HYDROXAMIC ACIDS; MODELS, MOLECULAR; PROTEASE INHIBITORS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 53949085531     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.045     Document Type: Article

References (29)

1. Killar L., White J., Black R., and Peschon J. J. Ann. NY Acad. Sci. 878 (1999) 442
2. Kriegler M., Perez C., Defay K., Albert I., and Lu S.D. Cell 53 (1988) 45
3. Black R.A., Rauch C.T., Kozlosky C.J., Peschon J.J., Slack J.L., Wolfson M.R., Castner B.J., Stocking K.L., Reddy P., Srinivasan S., Melson N., Bioiani N., Schooley K.A., Gerhart M., Davis R., Fitzner J.N., Johnson R.S., Paxton R.J., March C.J., and Cerretti D.P. Nature 385 (1997) 729
4. Moss M.L., Jin S.-L., Milla M.E., Bickett D.M., Burkhart W., Carter H.L., Chem W.J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R., Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan F., Mitchell J., Moyer M., Pahel G., Rocque W., Overton L.K., Schoenen R., Seaton T., Su J.L., and Becherer J.D. Nature 385 (1997) 733
5. Van Assche G., and Rutgeerts P. Exp. Opin. Invest. Drugs 9 (2000) 103
6. Nelson F.C., and Zask A. Exp. Opin. Invest. Drugs 8 (1999) 383
7. Doggrell S.A. Exp. Opin. Invest. Drugs 11 (2002) 1103
8. Feldmann M., Brennan F.M., Foxwell B.M., and Maini R.N. Curr. Dir. Autoimmun. 3 (2001) 188
9. Lipsky P.E., van der Heijde D.M., St. Clair E.W., Furst D.E., Breedveld F.C., Kalden J.R., Smolen J.S., Weisman M., Emery P., Feldman M., Harriman G.R., and Maini R.N. N. Engl. J. Med. 343 (1997) 1594
10. Bathon J.M., Martin R.W., Fleischmann R.M., Tesser J.R., Schiff M.H., Keystone E.C., Genovese M.C., Wasko M.C., Moreland L.W., Weaver A.L., Markenson J., and Finck B.K. N. Engl. J. Med. 343 (2000) 1586
11. Moreland L.W., Baumgartner S.W., Schiff M.H., Tindal E.A., Fleischmann R.M., Weaver A.L., Ettlinger R.E., Cohen S., Koopman W.J., Mohler K., Widmer M.B., and Blosch C.M. N. Engl. J. Med. 337 (1997) 141
12. For a recent review of TACE inhibitors, see. Skotnicki J.S., and Levin J.I. Ann. Rep. Med. Chem. 38 (2003) 153
13. Newton R.C., Solomon K.A., Covington M.B., Decicco C.P., Haley P.J., Friedman S.M., and Vaddi K. Ann. Rheum. Dis. 60 (2001) 25
14. Moss M.L., White J.M., Lambert M.H., and Andrews R.C. Drug Discov. Today 6 (2001) 417
15. Lukacova V., Zhang Y., Kroll D.M., Raha S., Comez D., and Balaz S. J. Med. Chem. 48 (2005) 2361
16. Maskos K., Fernandez-Catalan C., Huber R., Bourenkov G., Bartunik H., Ellestad G., Reddy P., Wolfson M., Rauch C., Castner B., Davis R., Clark H., Petersen M., Fitzner J., Cerratti D., March C., Paxton R., Black R., and Bode W. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 3408
17. Rush III T.S., and Powers R. Curr. Top. Med. Chem. 4 (2004) 1311
18. Renkiewicz R., Qiu L., Lesch C., Un X., Devalaraja R., Cody T., Kaldjian E., Welgus H., and Baragi V. Arthritis Rheum. 48 (2003) 1742
19. Duan J.J.-W., Chen L., Wasserman Z.R., Zhonghui L., Rui-Qin L., Covington M.B., Qian M., Hardman K.D., Magolda R.L., Newton R.C., Christ D.D., Wexler R.R., and Decicco C.P. J. Med. Chem. 45 (2002) 4954
20. Levin J.I., Chen J.M., Laakso L.M., Du M., Schmid J., Xu W., Cummons T., Xu J., Jin G., Barone D., and Skotnicki J.S. Bioorg. Med. Chem. Lett. 16 (2006) 1605
21. Levin J.I., Chen J.M., Laakso L.M., Du M., Du X., Venkatesan A.M., Sandanyaka V., Zask A., Xu J., Xu W., Zhang Y., and Skotnicki J.S. Bioorg. Med. Chem. Lett. 15 (2005) 4345
22. Zhu Z., Mazzola R., Sinning L., McKittrick B., Niu X., Lundell D., Sun J., Orth P., Guo Z., and Madison V. J. Med. Chem. 51 (2008) 725
23. Huang A., Joseph-McCarthy D., Lovering F., Sun L., Wang W., Xu W., Zhu Y., Cui J., Zhang Y., and Levin J.I. Bioorg. Med. Chem. 15 (2007) 6170
24. 1H NMR and MS in accord with their assigned structure. All final targets showed LCMS purities >95%.
25. Majid T.N., and Knochel P. Tetrahedron Lett. 31 (1990) 4413
26. Von der Saal W., Reinhardt R., Seidenspinner H.-M., Satwitz J., and Quast H. Liebigs Ann. Chem. (1989) 703
27. 2H, 86%.
28. For details concerning all in vitro assay conditions used herein, please see Ref. 12.
29. For experimental details of the pharmacokinetic assay, see:. Korfmacher W.A., Cox K.A., Ng K.J., Veals J., Hsieh Y., Weinhaus S., Broske L., Prelusky D., Nomeir A., and White R.E. Rapid Commun. Mass Spectrum 15 (2001) 335