Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 23, 2008, Pages 6293-6297

  Stiff, Cory ^a   Graber, David R ^a   Thorarensen, Atli ^a   Wakefield, Brian D ^a   Marotti, Keith R ^c   Melchior, Earline P ^c   Sweeney, Michael T ^c   Han, Fusen ^b   Rohrer, Douglas C ^b   Zurenko, Gary E ^c   Romero, Donna L ^a  

^a Medicinal Chemistry Research   (United States)

^b Pharmacia and Upjohn   (United States)

^c PFIZER INC   (United States)

Author keywords

Antibacterials; Bioisosteres; Indazol; Protein binding; Translation inhibitors

Indexed keywords

1 ACYLINDAZOL 3 OL; ANTHRANILIC ACID DERIVATIVE; INDAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANTHRANILIC ACIDS; ANTI-BACTERIAL AGENTS; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; INDAZOLES; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PROTEIN BIOSYNTHESIS; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP;

BACTERIA (MICROORGANISMS);

EID: 55549145405     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.08.041     Document Type: Article

References (12)

1. Unpublished results and Larsen, S. D.; Hester, M. R.; Ruble, J. C.; Kamilar, G. M.; Romero, D. L.; Wakefield, B.; Melchior, E. P.; Sweeney, M. T.; Marotti, K. R. Bioorg. Med. Chem. Lett. 2006, 16, 6173.
2. Ruble J.C., Wakefield B.D., Kamilar G.M., Marotti K.R., Melchior E.P., Sweeney M.T., Zurenko G.E., and Romero D.L. Bioorg. Med. Chem. Lett. 17 (2007) 4040
3. Translation inhibition was demonstrated by using mRNA (no DNA) in the assay described in Ref. 12.
4. Li J., Wakefield B.D., Ruble J.C., Stiff C.M., Romero D.L., Marotti K.R., Sweeney M.T., Zurenko G.E., Rohrer D.C., and Thorarensen A. Bioorg. Med. Chem. Lett. 17 (2007) 2347
5. Thorarensen A., Wakefield B.D.C.M., Romero D.L., Marotti K.R., Sweeney M.T., Zurenko G.E., Rohrer D.C., Han F., and Bryant G.L. Bioorg. Med. Chem. Lett. 17 (2007) 2823
6. Stiff C.M., Zhong M., Sarver R.W., Gao H., Ho A.M., Sweeney M.T., Zurenko G.E., and Romero* D.L. Bioorg. Med. Chem. Lett. 17 (2007) 2823
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8. Anderson R. J. Chem. Res., Synop. (1985) 376
9. 5S: C, 51.36; H, 2.81; N, 7.81. Found: C, 51.41; H, 2.89; N, 7.79.
10. Antibacterial activity does not fully correlate with activity in the T/T assay, indicating that the compounds may operate by an additional mechanism. See:. Mott J.E., Shaw B.A., Smith J.F., Bonin P.A., Romero D.L., Marotti K.R., and Miller A.A. J. Antimicrob. Chemother. 62 (2008) 720
11. Crystallographic data (excluding structure factors) for the structures in the paper have been deposited at the Cambridge Crystallographic Data Centre as CCDC 646068 & 646069.
12. Murray R.W., Melchior E.P., Hagadorn J.C., and Marotti K.R. Antimicrob. Agents Chemother. 45 (2001) 1900