Novel inhibitors of procollagen C-proteinase. Part 2: Glutamic acid hydroxamates

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 14, 2003, Pages 2381-2384

  Robinson, L A ^a   Wilson, D M ^a,d   Delaet, N G J ^a,c   Bradley, E K ^a,e   Dankwardt, S M ^b   Campbell, J A ^b,g   Martin, R L ^b   Van Wart, H E ^b,f   Walker, K A M ^b   Sullivan, R W ^a,c  

^a Formerly CombiChem Inc   (United States)

^b ROCHE BIOSCIENCE   (United States)

^c Kemia Inc   (United States)

^d VERTEX PHARMACEUTICALS   (United States)

^e Sunesis Pharmaceuticals Inc   (United States)

^f Metabolex   (United States)

^g BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; FIBRILLAR COLLAGEN; HYDROXAMIC ACID DERIVATIVE; PROCOLLAGEN C PROTEINASE; PROCOLLAGEN C PROTEINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG SCREENING; DRUG TARGETING; FIBROSIS;

EID: 12444285442     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00402-5     Document Type: Article

References (24)

1. Franklin T.J. Int. J. Biochem. Cell Biol. 29:1997;79.
2. Prockop D.J., Kivirikko K.I. Annu. Rev. Biochem. 64:1995;403.
3. Nahas A.M.E., Muchaneta-Kubara E.C., Essawy M., Soylemezoglu O. Int. J. Biochem. Cell Biol. 29:1997;55.
4. McCrudden R., Iredale J.P. Histol. Histopathol. 15:2000;1159.
5. Okazaki I., Watanabe T., Hozawa S., Arai M., Maruyama K. J. Gastroenterol. Hepatol. 15(Suppl.):2000;D26.
6. (a) Norman P. Exp. Opin. Ther. Pat. 11:2001;307
7. (b) Norman P. Exp. Opin. Ther. Pat. 8:1998;1.
8. Rerolle J.-P., Hertig A., Nguyen G., Sraer J.-D., Rondreau E.P. Kidney Int. 58:2000;1841.
9. Bond J., Beynon R.J. Protein Sci. 4:1995;1247.
10. Stoecker A., Grams F., Baumann U., Reinemer P., Gomis- Ruth F.S., McKay D.B., Bode W. Protein Sci. 4:1995;823.
11. Li S.W., Sieron A.L., Fertala A., Hojima Y., Arnold W.V., Prockop D.J. Proc. Natl. Acad. Sci. U.S.A. 93:1996;5127.
12. Ovens, A.; Joule, J.A.; Kadler, K.E. J. Pept. Sci. 2000, 6,489. Since this work, other researchers have identified hydroxamates as inhibitors of PCP. See for example: Brenner, M.; Ho, W.-B. PCT application WO97/05865. Bailey S., Billotte, S.; Derrick, A. M.; Fish, P. V.; James, K.; Thomson, N. M. PCT application WO01/47901. Ho W.-B.; Bauer, U. PCT application WO01/56996.
13. Ovens, A.; Joule, J.A.; Kadler, K.E. J. Pept. Sci. 2000, 6,489. Since this work, other researchers have identified hydroxamates as inhibitors of PCP. See for example: Brenner, M.; Ho, W.-B. PCT application WO97/05865. Bailey S., Billotte, S.; Derrick, A. M.; Fish, P. V.; James, K.; Thomson, N. M. PCT application WO01/47901. Ho W.-B.; Bauer, U. PCT application WO01/56996.
14. Delaet, N. G. J.; Robinson, L. A.; Wilson, D. M.; Sullivan, R. W.; Bradley, E. K.; Dankwardt, S. M.; Martin, R. L.; Van Wart, H. E.; Walker, K. A. M. Bioorg. Med. Chem. Lett. 2003, 13, 2101.
15. Mellor S.L., McGuire C., Chan W.C. Tetrahedron Lett. 38:1997;3311.
16. 3P (3 equiv) and 1,1′-(azodicarbonyl)dipiperidine (ADDP) (3 equiv) was stirred for 2 min. Piperonyl alcohol (5 equiv) was added and the mixture stirred for 1 min longer, then added to the resin which had been pre-swollen with DCM for 20 min. The reaction was shaken at room temperature overnight.
17. Hoekstra W.J., Greco M.N., Yabut S.C., Hulshizer B.L., Maryanoff B.E. Tertahedron Lett. 38:1997;2629.
18. Ester deprotection protocol: The resin was swollen with DCM and sparged with nitrogen for 20 min, then filtered. A solution of potassium trimethyl silanolate (5-7 equiv) in anhydrous THF was added to the resin, and the reaction shaken for 2 h. The mixture was filtered and the resin dried to allow distribution.
19. Library synthesis protocol: 150-200 mg of resin was distributed in each well of a 48-well filter plate using the Robbins FlexChem® system and swollen with DCM. The appropriate amine monomer (3-4 equiv, 1 M in DMF), pre-mixed HATU/HOAt (3 equiv, 0.5 M in each in DMF), and DIEA (6 equiv) were added to each well. The plate was shaken on a platform shaker overnight. Products were cleaved from the resin with 10% TFA/DCM.
20. Shapiro G., Buechler D. Tetrahedron Lett. 35:1994;5421.
21. Zeng L., Kassel D.B. Anal. Chem. 70:1998;4380.
22. PCP and MMP assay protocols are described in Billedeau, R. J.; Broka, C. A.; Campbell, J. A.; Chen, J. J.; Dankwardt, S. M.; Delaet, N.; Robinson, L. A.; Walker, K. A. M., PCT application WO00/37436.
23. Kiyama R., Tamura Y., Watanabe F., Tsuzuki H., Ohtani M., Yodo M. J. Med. Chem. 42:1999;1723.
24. Dankwardt S.M., Martin R.L., Chan C.S., Van Wart H.E., Walker K.A.M., Delaet N., Robinson L.A. Bioorg. Med. Chem. Lett. 11:2001;2085.