4-Alkyl and 4,4'-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives as new inhibitors of bacterial cell wall biosynthesis.
Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against gram-positive bacteria, particularly penicillin-resistant Streptococcus pneumoniae (PRSP). Derivative 7l demonstrated antibacterial activity against both gram-positive and gram-negative bacteria. Derivatives 7f and 10a also demonstrated potent nanomolar Kd values in their binding to MurB.
Kutterer
Kristina M K
KM
Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Rd, Pearl River, NY 10965, USA. kutterk@wyeth.com
Davis
Jamie M
JM
Singh
Guy
G
Yang
Youjun
Y
Hu
William
W
Severin
Anatoly
A
Rasmussen
Beth A
BA
Krishnamurthy
Girija
G
Failli
Amedeo
A
Katz
Alan H
AH
D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D011720:Pyrazoles / Q000494:pharmacology*
D011720:Pyrazoles; C443742:pyrazolidine-3,5-dione