Exploring 8-benzyl pteridine-6,7-diones as inhibitors of glutamate racemase (MurI) in Gram-positive bacteria

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 23, 2008, Pages 6100-6103

  Breault, Gloria A ^a   Comita Prevoir, Janelle ^a   Eyermann, Charles J ^a   Geng, Bolin ^a   Petrichko, Randy ^a   Doig, Peter ^a   Gorseth, Elise ^a   Noonan, Brian ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

8 Benzyl pteridine 6,7 dione; Glutamate racemase; MurI inhibitor

Indexed keywords

8 BENZYLPTERIDINE 6,7 DIONE; ANTIINFECTIVE AGENT; BACTERIAL ENZYME; BENZYL DERIVATIVE; GLUTAMATE RACEMASE; GLUTAMATE RACEMASE INHIBITOR; PTERIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ALLOSTERISM; ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG POTENCY; ENTEROCOCCUS FAECALIS; GRAM POSITIVE BACTERIUM; IC 50; NONHUMAN; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

AMINO ACID ISOMERASES; ANTI-BACTERIAL AGENTS; COMBINATORIAL CHEMISTRY TECHNIQUES; GRAM-POSITIVE BACTERIA; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; PTERIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

BACTERIA (MICROORGANISMS); POSIBACTERIA;

EID: 55749104390     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.10.022     Document Type: Article

References (21)

1. Bush K. Clin. Microbiol. Infect. 10 (2004) 10
2. Payne D.J., Gwynn M.N., Holmes D.J., and Rosenberg M. Methods Mol. Biol. 266 (2004) 231
3. Doublet P., van Heijenoort J., and Mengin-Lecreulx D. J. Bacteriol. 174 (1992) 5772
4. Glavas S., and Tanner M.E. Biochemistry 40 (2001) 6199
5. Doublet P., van Heijenoort J., and Mengin-Lecreulx D. Biochemistry 33 (1994) 5285
6. Van Heijenoort J. Nat. Prod. Rep. 18 (2001) 503
7. For investigation of structural and regulatory diversity of glutamate racemases, see. Lundqvist T., Fisher S.L., Kern G., Folmer R.H.A., Xue Y., Newton D.T., Keating T.A., Alm R., and de Jonge B.L.M. Nature 447 (2007) 817
8. Geng B., Breault G., Comita-Prevoir J., Petrichko R., Eyermann J.C., Doig P., Gorseth E., and Noonan B. Bioorg. Med. Chem. Lett. 18 (2008) 4368
9. For case studies of scaffold-hopping, see. Hall A., Billinton A., Brown S.H., Chowdhury A., Giblin G.M.P., Goldsmith P., Hurst D.N., Naylor A., Patel S., Scoccitti T., and Theobald P.J. Bioorg. Med. Chem. Lett. 18 (2008) 2684
10. Feher M., Gao Y., Baber J.C., Shirley W.A., and Saunders J. Bioorg. Med. Chem. 16 (2008) 422
11. Larbig G., Pickhardt M., Lloyd D.G., Schmidt B., and Mandelkow E. Curr. Alzheimer Res. 4 (2007) 315
12. O'Meara J.A., Jakalian A., LaPlante S., Bonneau P.R., Coulombe R., Paucher A.-M., Suse I., Landry S., Racine J., Simoneau B., Thavonek B., and Yoakim C. Bioorg. Med. Chem. Lett. 17 (2007) 3362
13. Bostroem J., Berggren K., Elebring T., Greaslye P.J., and Wilstermann M. Bioorg. Med. Chem. 15 (2007) 4077
14. For reviews of scaffold-hopping, see. Zhao H. Drug Discovery Today 12 (2007) 149
15. Schneider G., Schneider P., and Renner S. QSAR Comb. Sci. 25 (2006) 1162
16. Brown N., and Jacoby E. Mini-Rev. Med. Chem. 6 (2006) 1217
17. 50s were determined for E. faecalis and S. aureus glutamate racemase at pH 8 in the presence of Tris buffer containing polyethylene glycol, dithiothreitol and d-glutamate. The conversation of d-glutamate to l-glutamate was monitored by HPLC using chiral separation of the glutamate enantiomers on a Phenomenex Chirex (d)-Penicillamine column.
18. Forrest H.S., Hull R., Rodda H.J., and Todd A.R. J. Chem. Soc. (1951) 3
19. Bonnert, R. V.; Cage, P. A.; Hunt, S. F.; Walters, I. A. S.; Austin, R. P. PCT Int. Appl. WO 2003024966, 2003.
20. Walters I., Austin C., Austin R., Bonnert R., Cage P., Christie M., Ebden M., Gardiner S., Grahames C., Hill S., Hunt F., Jewell R., Lewis S., Martin I., Nicholls D., and Robinson D. Bioorg. Med. Chem. Lett. 18 (2008) 798
21. McMartin C., and Bohacek R.S. J. Comput. Aided Mol. Des. 11 (1997) 333