Discovery of a novel azaindole class of antibacterial agents targeting the ATPase domains of DNA gyrase and Topoisomerase IV

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 15, 2012, Pages 5150-5156

  Manchester, John I ^a   Dussault, Daemian D ^a   Rose, Jonathan A ^a   Boriack Sjodin, P Ann ^a   Uria Nickelsen, Maria ^a   Ioannidis, Georgine ^a   Bist, Shanta ^a   Fleming, Paul ^a   Hull, Kenneth G ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Antibacterial; Azaindole; DNA gyrase; Structure based design

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ANTIINFECTIVE AGENT; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE IV; INDOLE DERIVATIVE; LEVOFLOXACIN; NOVOBIOCIN;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROGEN BOND; HYDROPHOBICITY; IC 50; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; MUTATION; NONHUMAN; STREPTOCOCCUS PNEUMONIAE; STRUCTURE ACTIVITY RELATION;

ADENOSINE TRIPHOSPHATASES; ANTI-BACTERIAL AGENTS; AZA COMPOUNDS; BACTERIAL PROTEINS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DNA GYRASE; DNA TOPOISOMERASE IV; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, BACTERIAL; ENZYME INHIBITORS; INDOLES; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL SENSITIVITY TESTS; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP;

BACTERIA (MICROORGANISMS); STAPHYLOCOCCUS AUREUS;

EID: 84863956207     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.05.128     Document Type: Article

References (23)

1. C.G. Giske, D.L. Monnet, O. Cars, and Y. Carmeli ReAct-Action on Antibiotic Resistance Antimicrob Agents Chemother. 52 2008 813
2. H.W. Boucher, G.H. Talbot, J.S. Bradley, J.E. Edwards, D. Gilbert, L.B. Rice, M. Scheld, B. Spellberg, and J. Bartlett Clin. Infect. Dis. 48 2009 1
3. B. Spellberg, R. Guidos, D. Gilbert, J. Bradley, H.W. Boucher, W.M. Scheld, J.G. Bartlett, and J. Edwards Jr Clin. Infect. Dis. 46 2008 155
4. P.S. Charifson, A.L. Grillot, T.H. Grossman, J.D. Parsons, M. Badia, S. Bellon, D.D. Deininger, J.E. Drumm, C.H. Gross, A. LeTiran, Y. Liao, N. Mani, D.P. Nicolau, E. Perola, S. Ronkin, D. Shannon, L.L. Swenson, Q. Tang, P.R. Tessier, S.K. Tian, M. Trudeau, T. Wang, Y. Wei, H. Zhang, and D. Stamos J. Med. Chem. 51 2008 5243
5. Basarab, G. S.; Bist, S.; Manchester, J. I.; Sherer, B. 2008, U.S. Patent Appl. Publ. US20080132546A1.
6. Boriack-Sjodin, A.; Carcanague, D. R.; Dussault, D. D.; Hatoum-Mokdad, H.; Hull, K. G.; Ioannidis, G.; Manchester, J. I.; McGuire, H. M.; McKinney, D. C.; Stokes, S. 2010, PCT Int. Appl. WO2010038081A2.
7. S.P. East, C.B. White, O. Barker, S. Barker, J. Bennett, D. Brown, E.A. Boyd, C. Brennan, C. Chowdhury, I. Collins, E. Convers-Reignier, B.W. Dymock, R. Fletcher, D.J. Haydon, M. Gardiner, S. Hatcher, P. Ingram, P. Lancett, P. Mortenson, K. Papadopoulos, C. Smee, H.B. Thomaides-Brears, H. Tye, J. Workman, and L.G. Czaplewski Bioorg. Med. Chem. Lett. 19 2009 894
8. D.B. Wigley, G.J. Davies, E.J. Dodson, A. Maxwell, and G. Dodson Nature 351 1991 624
9. D. Lafitte, V. Lamour, P.O. Tsvetkov, A.A. Makarov, M. Klich, P. Deprez, D. Moras, C. Briand, and R. Gilli Biochemistry (N.Y.) 41 2002 7217
10. S. Bellon, J.D. Parsons, Y. Wei, K. Hayakawa, L.L. Swenson, P.S. Charifson, J.A. Lippke, R. Aldape, and C.H. Gross Antimicrob. Agents Chemother. 2004 1856 48
11. C. Chuaqui, Z. Deng, and J. Singh J. Med. Chem. 48 2005 121
12. B.A. Sherer, K. Hull, O. Green, G. Basarab, S. Hauck, P. Hill, J.T. Loch 3rd, G. Mullen, S. Bist, J. Bryant, A. Boriack-Sjodin, J. Read, N. DeGrace, M. Uria-Nickelsen, R.N. Illingworth, and A.E. Eakin Bioorg. Med. Chem. Lett. 21 2011 7416
13. H.J. Boehm, M. Boehringer, D. Bur, H. Gmuender, W. Huber, W. Klaus, D. Kostrewa, H. Kuehne, T. Luebbers, N. Meunier-Keller, and F. Mueller J. Med. Chem. 43 2000 2664
14. S. Firth-Clark, N.P. Todorov, I.L. Alberts, A. Williams, T. James, and P.M. Dean J. Chem. Inf. Model. 46 2006 1168
15. M. Oblak, S.G. Grdadolnik, M. Kotnik, R. Jerala, M. Filipic, and T. Solmajer Bioorg. Med. Chem. Lett. 15 2005 5207
16. G. Jones, P. Willett, R.C. Glen, A.R. Leach, and R. Taylor J. Mol. Biol. 267 1997 727
17. G. Jones, P. Willett, and R.C. Glen J. Mol. Biol. 245 1995 43
18. A.E. Eakin, O. Green, N. Hales, G.K. Walkup, S. Bist, A. Singh, G. Mullen, J. Bryant, K. Embrey, N. Gao, A. Breeze, D. Timms, B. Andrews, M. Uria-Nickelsen, J. Demeritt, J.T. Loch 3rd, K. Hull, A. Blodgett, R.N. Illingworth, B. Prince, P.A. Boriack-Sjodin, S. Hauck, L.J. MacPherson, H. Ni, and B. Sherer Antimicrob. Agents Chemother. 56 2012 1240
19. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas Foresman. J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. gaussian 09, Revision B.01, gaussian, Inc., Wallingford CT 2009.
20. A. L'Heureux, C. Thibault, and R. Ruel Tetrahedron Lett. 45 2004 2317
21. N. Miyaura, K. Yamada, and A. Suzuki Tetrahedron Lett. 20 1979 3437
22. Clinical and Laboratory Standards Institute Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard, 9th Ed. M07-A8; Clinical and Laboratory Standards Institute: Wayne, PA., 2009.
23. H. Fukuda, and K. Hiramatsu Antimicrob. Agents Chemother. 43 1999 410