Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 9, 2010, Pages 2828-2831

  Ronkin, Steven M ^a   Badia, Michael ^a   Bellon, Steve ^b   Grillot, Anne Laure ^a   Gross, Christian H ^a   Grossman, Trudy H ^c   Mani, Nagraj ^a   Parsons, Jonathan D ^a   Stamos, Dean ^a   Trudeau, Martin ^a   Wei, Yunyi ^a   Charifson, Paul S ^a  

^a VERTEX PHARMACEUTICALS   (United States)

^b Department of Structural Biology   (United States)

^c Tetraphase Pharmaceuticals Inc   (United States)

Author keywords

Antibacterials; Bacterial gyrase

Indexed keywords

2 (PYRIDIN 3 YL)THIAZOLE PYRAZOLE; 2 PIPERIDINE; 5 (1H PYRAZOL 3 YL)THIAZOLE DERIVATIVE; ANTIINFECTIVE AGENT; CARBAMIC ACID DERIVATIVE; DNA TOPOISOMERASE (ATP HYDROLYSING) B; GYRASE INHIBITOR; PIPERIDINE DERIVATIVE; PROPARGYLCARBAMATE; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL STRAIN; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; ESCHERICHIA COLI; NONHUMAN; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; X RAY CRYSTALLOGRAPHY;

ANTI-BACTERIAL AGENTS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DNA GYRASE; ENZYME INHIBITORS; MICROBIAL SENSITIVITY TESTS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI;

EID: 77950865528     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.03.052     Document Type: Article

References (12)

1. Barrett C.T., and Barrett J.F. Curr. Opin. Biotechnol. 14 (2003) 621
2. Wolfson J.S., and Hooper D.C. Antimicrob. Agents Chemother. 28 (1985) 581
3. Ho P.-L., Que T.-L., Tsang D.N.-C., Ng T.-K., Chow K.-H., and Seto W.-H. Antimicrob. Agents Chemother. 43 (1999) 1310
4. Drlica K., Malik M., Kerns R.J., and Zhao X. Antimicrob. Agents Chemother. 52 (2008) 385
5. Lewis I.J., Singh O.M.P., Smith C.V., Skarzynski T., Maxwell A., Wonacott A.J., and Wigley D.B. EMBO J. 15 (1996) 1412
6. Hull, K.; Green, O.; Sing, A.; Bist, S.; Demeritt, J.; Loch, J.; Mulled, G.; Hauk, S.; Sherer, B.; Ni, H.; Eakin, A.E. Presented at the 48th Interscience Conference on Antimicrobial Agents, Washington D.C., October, 2008; Poster F1-2027.
7. Illingworth, R.N.; Uria-Nickelsen, M.; Bryant, J.; Eakin, A.E. Presented at the 48th Interscience Conference on Antimicrobial Agents, Washington D.C., October 2008; Poster F1-2028.
8. Charifson P.S., Grillot A.-L., Grossman T.H., Parsons J.D., Badia M., Bellon S., Deininger D.D., Drumm J.E., Gross C.H., LeTiran A., Liao Y., Mani N., Nicolau D.P., Perola E., Ronkin S., Shannon D., Swenson L.L., Tang Q., Tessier P.R., Tian S.-K., Trudeau M., Wang T., Wei Y., Zhang H., and Stamos D. J. Med. Chem. 51 (2008) 5243
9. Holmquist C.R., and Roskamp E.J. J. Org. Chem. 54 (1989) 3258
10. Kerdesky F.A.J., Holms J.H., Moore J.L., Bell R.L., Dyer R.D., Carter G.W., and Brooks D.W. J. Med. Chem. 34 (1991) 2158-2165
11. Sakamoto T., Shiga F., Uchiyama D., Kondo Y., and Yamanaka H. Heterocycles 33 (1992) 813-818
12. For full experimental details on similar compounds see: US Patent 0024030 A1, 2005.