1-Hydroxy-2-pyridinone-based MMP inhibitors: Synthesis and biological evaluation for the treatment of ischemic stroke

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 1, 2008, Pages 409-413

  Zhang, Yue Mei ^a   Fan, Xiaodong ^a   Chakaravarty, Devraj ^a   Xiang, Bangping ^b   Scannevin, Robert H ^a   Huang, Zhihong ^a   Ma, Jianya ^a   Burke, Sharon L ^a   Karnachi, Prabha ^c   Rhodes, Kenneth J ^a   Jackson, Paul F ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c HOFFMANN LA ROCHE INC   (United States)

Author keywords

1 Hydroxy 2 pyridone; Matrix metalloproteinase inhibitor; MMP 9; Stroke

Indexed keywords

1 HYDROXY 2 PYRIDINONE DERIVATIVE; COLLAGENASE 3; GELATINASE A; GELATINASE B; INTERSTITIAL COLLAGENASE; MATRIX METALLOPROTEINASE INHIBITOR; STROMELYSIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; DISTRIBUTION VOLUME; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; IN VITRO STUDY; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NONHUMAN;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; BRAIN ISCHEMIA; DISEASE MODELS, ANIMAL; INHIBITORY CONCENTRATION 50; MALE; MATRIX METALLOPROTEINASE 2; MATRIX METALLOPROTEINASE 9; MICE; MICE, INBRED C57BL; MODELS, MOLECULAR; PROTEASE INHIBITORS; PYRIDONES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; ZINC;

EID: 37549033505     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.10.045     Document Type: Article

References (22)

1. Rosenberg G.A., Estrada E.Y., and Dencoff J.E. Stroke 29 (1998) 2189
2. Aranapakam V., Davis J.M., Grosu G.T., Baker J., Ellingboe J., Zask A., Levin J.I., Sandanayaka V.P., Du M., Skotnicki J.S., and DiJoseph J.F. J. Med. Chem. 46 (2003) 2376
3. Coussens L.M., Fingleton B., and Martrisian L.M. Science 295 (2002) 2387
4. For a recent review, see:. Jacobsen F.E., Lewis J.A., and Cohen S.M. ChemMedChem 2 (2007) 152
5. Breuer E., Frant J., and Reich R. Expert Opin. Ther. Pat. 15 (2005) 253
6. For related references, see: Eriksson, A.; Lepisto, M.; Lundkvist, M.; Munck af Rosenschold, M.; Stenvall, K.; Zlatoidsky, P. WO 03/040098 A1.
7. Ma D.-W., Wu W.-G., Qian J., Lang S.-H., and Ye Q.-Z. Chin. J. Chem. 19 (2001) 286
8. Puerta D.T., and Cohen S.M. Inorg. Chem. 42 (2003) 3423
9. Puerta D.T., Lewis J.A., and Cohen S.M. J. Am. Chem. Soc. 126 (2004) 8388
10. Puerta, D. T.; Cohen, S. M.; Lewis, J. A. US 2007/0117848 A1.
11. Puerta D.T., Mongan J., Tran B.L., McCammon J.A., and Cohen S.M. J. Am. Chem. Soc. 127 (2005)
12. Yan Y.-L., and Cohen S.M. Org. Lett. 9 (2007) 2517
13. Matter H., and Schudok M. Curr. Opin. Drug Discovery Dev. 7 (2004) 513
14. Caron S., Do N.M., and Sieser J.E. Tetrahedron Lett. 41 (2000) 2299
15. Dong L., and Miller M. J. Org. Chem. 67 (2002) 4759
16. The homology model of MMP9 was build using a crystal structure of MMP2 and using the software Prime and refined using Macromodel. The compounds were docked into the active site using the software GLIDE (Glide 3.5, Prime 1.4, Macromodel from Schrodinger, New York. 2005). No scaling factors were applied to the van der Waals radii. Default settings were used for all the remaining parameters. The top 20 poses based on Glidescore were energy-minimized with Macromodel using the OPLS-AA force field, and the refined poses reranked using Glidescore.
17. Walz A.J., and Miller M. J. Org. Lett. 4 (2002) 2047
18. Xu Y., and Miller M.J. J. Org. Chem. 63 (1998) 4314
19. Hu J., and Miller M.J. J. Am. Chem. Soc 119 (1997) 3462
20. For the protocol for tMCAO model, see supplemental material and the following:. Zea-Longa E., Weinstein P.R., Carlson S., and Cummin R.W. Stroke (1989) 2084
21. Huang Z., Huang P.L., Panahian N., Dalkara T., Fishman M.C., and Moskowitz M.A. Science 265 (1994) 1883
22. Hara H., Huang P.L., Panahian N., Fishman M.C., and Moskowitz M.A. J. Cereb. Blood Flow Metab. 16 (1996) 605