Structure-activity relationships of the peptide deformylase inhibitor BB-3497: Modification of the P2′ and P3′ side chains

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 16, 2003, Pages 2715-2718

  Davies, Stephen J ^a   Ayscough, Andrew P ^a   Beckett, R Paul ^a   Clements, John M ^a   Doel, Sheila ^a   Pratt, Lisa M ^a   Spavold, Zoë M ^a   Thomas, S Wayne ^a   Whittaker, Mark ^a  

^a British Biotech Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

N (1 TERT BUTYL 2 DIMETHYLAMINO 2 OXOETHYL) 2 (N FORMYL N HYDROXYAMINOMETHYL)HEXANAMIDE; PEPTIDE DEFORMYLASE INHIBITOR;

ANTIBACTERIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; ENZYME INHIBITION; ESCHERICHIA COLI; NONHUMAN; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 0037811323     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00533-X     Document Type: Article

References (16)

1. Livingston J.M., Leber P. Biochemistry. 8:1969;435.
2. (a) Pei D. Emerg. Ther. Targets. 5:2001;23.
3. (b) Giglione C., Meinnel T. Emerg. Ther. Targets. 5:2001;41.
4. (c) Yuan Z., Trias J., White R. J. Drug Discov. Today. 6:2001;955.
5. Clements J.M., Ayscough A.P., Keavey K., East S.P. Curr. Med. Chem.-Anti-Infect. Agents. 1:2002;239.
6. Clements J.M., Beckett R.P., Brown A., Catlin G., Lobell M., Palan S., Thomas W., Whittaker M., Wood S., Salama S., Baker P.J., Rodgers H.F., Barynin V., Rice D.W., Hunter M.G. Antimicrob. Agents Chemother. 45:2001;563.
7. Smith H.K., Beckett R.P., Clements J.M., Doel S., East S.P., Launchbury S.B., Pratt L.M., Spavold Z.M., Thomas W., Todd R.S., Whittaker M. Bioorg. Med. Chem. Lett. 12:2002;3595.
8. Chan M.K., Gong W., Rajagopalan P.T.R., Hao B., Tsai C.M., Pei D. Biochemistry. 36:1997;13904.
9. Becker A., Schlichting I., Kabsch W., Groche D., Schultz S., Wagner A.F. Nat. Struct. Biol. 5:1998;1053.
10. Becker A., Schlichting I., Kabsch W., Schultz S., Wagner A.F. J. Biol. Chem. 273:1998;11413.
11. Meinnel T., Patiny L., Ragusa S., Blanquet S. Biochemistry. 38:1999;4287.
12. Guilloteau J.P., Mathieu M., Giglione C., Blanc V., Dupuy A., Chevrier M., Gil P., Famechon A., Meinnel T., Mikol V. J. Mol. Biol. 320:2002;951.
13. Davies, S. J.; Ayscough, A. P.; Beckett, R. P.; Bragg, R. A.; Clements, J. M.; Doel, S.; Grew, C.; Launchbury, S. B.; Perkins, G. M.; Pratt, L. M.; Smith, H. K.; Spavold, Z. M.; Thomas, S. W.; Todd, R. S.; Whittaker, M. Bioorg. Med. Chem. Lett. See preceding article. doi:10.1016/S0960-894X(3)00532-8.
14. Pratt L.M., Beckett R.P., Davies S.J., Launchbury S.B., Miller A., Spavold Z.M., Todd R.S., Whittaker M. Bioorg. Med. Chem. Lett. 11:2001;2585.
15. 4.
16. The methyl ester analogue 8a was prepared from esterification of Cbz-L-tert-leucine using diazomethane in dichloromethane. Saponification at the final stage of the synthesis afforded the carboxylic acid 8b. The ketone compound 8c was prepared by MeLi addition to the corresponding Weinreb amide.