Structure-activity relationships of the peptide deformylase inhibitor BB-3497: Modification of the methylene spacer and the P1′ side chain

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 16, 2003, Pages 2709-2713

  Davies, Stephen J ^a   Ayscough, Andrew P ^a   Beckett, R Paul ^a   Bragg, Ryan A ^a   Clements, John M ^a   Doel, Sheila ^a   Grew, Christine ^a   Launchbury, Steven B ^a   Perkins, Gemma M ^a   Pratt, Lisa M ^a   Smith, Helen K ^a   Spavold, Zoë M ^a   Thomas, S Wayne ^a   Todd, Richard S ^a   Whittaker, Mark ^a  

^a British Biotech Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

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

ANTIBACTERIAL ACTIVITY; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; ENZYME INHIBITION; ESCHERICHIA COLI; LIPOPHILICITY; NONHUMAN; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 12444268598     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00532-8     Document Type: Article

References (20)

1. Yuan Z., Trias J., White R. J. Drug Discov. Today. 6:2001;955.
2. (a) Pei D. Emerg. Ther. Targets. 5:2001;23.
3. (b) Giglione C., Meinnel T. Emerg, Ther. Targets. 5:2001;41.
4. (c) Giglione C., Meinnel T. Exp. Opin. Ther. Targets. 5:2001;415
5. (d) 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. 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.
12. (a) The succinate portion of compound 1 was prepared by employing an asymmetric alkylation on an Evans N-hexanoyl oxazolidinone with t-butyl bromoacetate. See: Beckett R.P., Crimmin M.J., Davis M.H., Spavold Z. Synlett. 1993;137 (b) Evans D.A., Ennis M.D., Mathre D.J. J. Am. Chem. Soc. 104:1982;1737.
13. (a) The succinate portion of compound 1 was prepared by employing an asymmetric alkylation on an Evans N-hexanoyl oxazolidinone with t-butyl bromoacetate. See: Beckett R.P., Crimmin M.J., Davis M.H., Spavold Z. Synlett. 1993;137 (b) Evans D.A., Ennis M.D., Mathre D.J. J. Am. Chem. Soc. 104:1982;1737.
14. Katritzky A.R., Chang H.-K., Yang B. Synthesis. 1995;503.
15. Davies, S. J.; Ayscough, A. P.; Beckett, R. P.; Clements, J. M.; Doel, S.; Pratt, L. M.; Spavold, Z. M.; Thomas, W.; Whittaker, M. Bioorg. Med. Chem. Lett. See following article. doi 10.1016-S0960-894X(03)00533-X.
16. Evans D.A., Morrissey M.M., Dorow R.L. J. Am. Chem. Soc. 107:1985;4346.
17. 18 Phenomenex Luna 50×4.6 mm HPLC column, the (R)-diastereomer always eluted before the corresponding (S)-diastereomer. For a select number of compounds, both diastereoisomers of the N-formyl hydroxylamine derivative 23 were assayed against the PDF·Ni enzyme and the more active diastereoisomer assigned the designated stereochemistry.
18. British Biotech Pharmaceuticals. Patent Application WO 99/39704, Aug. 12, 1999.
19. 3.
20. 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.