4-Alkyl and 4,4′-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5- dione derivatives as new inhibitors of bacterial cell wall biosynthesis

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 10, 2005, Pages 2527-2531

  Kutterer, Kristina M K ^a   Davis, Jamie M ^a   Singh, Guy ^b   Yang, Youjun ^b   Hu, William ^b   Severin, Anatoly ^b   Rasmussen, Beth A ^b   Krishnamurthy, Girija ^a   Failli, Amedeo ^c   Katz, Alan H ^c  

^a WYETH RESEARCH   (United States)

^b Wyeth   (United States)

^c PFIZER INC   (United States)

Author keywords

Antibacterial activity; Microwave assisted synthesis; MurA; MurB; Pyrazolidinediones

Indexed keywords

ANTIINFECTIVE AGENT; BACTERIAL ENZYME;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL CELL WALL; BIOSYNTHESIS; DRUG ACTIVITY; DRUG BINDING; DRUG SYNTHESIS; EVALUATION; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; MICROWAVE RADIATION; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PENICILLIN RESISTANCE; STREPTOCOCCUS PNEUMONIA;

BACTERIA (MICROORGANISMS); NEGIBACTERIA; POSIBACTERIA; STREPTOCOCCUS PNEUMONIAE;

EID: 20944432485     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.03.058     Document Type: Article

References (13)

1. K.K. Wong, and D.L. Pompiano B.P. Rosen S. Mobashery Resolving the Antibiotic Paradox: Progress in Understanding Drug Resistance and Development of New Antibiotics 1998 Plenum NY 197 217
2. R.C. Goldman, and A. Branson Curr. Pharm. Design 5 1999 473
3. K. Isono, M. Uramoto, H. Kusakabe, K. Kimura, K. Izaki, C.C. Nelson, and J.A. McCloskey J. Antibiot. 38 1985 1617
4. K. Kimura, Y. Ikeda, S. Kagami, and M. Yoshihara J. Antibiot. 51 1998 1099
5. N.R. El-Rayyes, and N.A. Al-Awadi Synthesis 11 1985 1028
6. 6, 400 MHz): δ 3.78 (s, 2H), 7.32 (m, 4H), 7.42 (m, 4H), MS [(-)ESI, m/z]: 319.1 [M-H]
7. D.V. Banthorpe, and A. Cooper J. Chem. Soc. B 6 1968 608
8. C.M. Baldwin, P.S. Song, and H.J. Shine J. Am. Chem. Soc. 92 1970 3284
9. S. Oae, N. Tsujimoto, and A. Nakanishi Bull. Chem. Soc. Jpn. 46 1973 535
10. 18 2.1 mm × 30 mm column, 3.5 μ particle size, at 50°C, water-acetonitrile solvent system with added 0.02% TFA buffer at 1.0 mL/min flow rate, 254 nm DAD detection; API-ES scanning mode, fragmentor 140 mV): 7g m/z 455.0 (M+H); retention time 3.279 min, 8b m/z 589.1 (M+H); retention time 3.622 min]
11. 50s were then estimated by linear regression analysis using the percent inhibition data bracketing 50% inhibition
12. 50 values were derived using data analysis function of Microsoft Excel program (Sigmoid Curve Hill analysis 0-100)
13. MICs: The in vitro determination of the MICs against aerobic bacteria was performed by the microdilution broth method as recommended by the National Committee for Clinical Laboratory Standards (Approved Standards M7 - A3, 1997). Mueller-Hinton Broth was used for the Staphylococci, and Enterococci. Streptococci were tested in Mueller-Hinton Broth supplemented with 5% sheep blood. Microtiter plates containing 50 μL sheep blood per well of 2-fold serial dilutions of the antibacterial agents in the appropriate broth were inoculated with 50 μL of inoculum to yield a final density of 1-5 × 105 CFU/mL. The MICs were determined after 18-22 h of incubation at 35°C in ambient air