title: 4-Alkyl and 4,4'-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives as new inhibitors of bacterial cell wall biosynthesis.
abstract: 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.
authors.affiliation: Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Rd, Pearl River, NY 10965, USA. kutterk@wyeth.com
authors.forename: Kristina M K
authors.initials: KM
authors.lastname: Kutterer
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Davis
authors.forename: Guy
authors.initials: G
authors.lastname: Singh
authors.forename: Youjun
authors.initials: Y
authors.lastname: Yang
authors.forename: William
authors.initials: W
authors.lastname: Hu
authors.forename: Anatoly
authors.initials: A
authors.lastname: Severin
authors.forename: Beth A
authors.initials: BA
authors.lastname: Rasmussen
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Amedeo
authors.initials: A
authors.lastname: Failli
authors.forename: Alan H
authors.initials: AH
authors.lastname: Katz
mesh_terms: D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D011720:Pyrazoles / Q000494:pharmacology*
chemical_list: D011720:Pyrazoles; C443742:pyrazolidine-3,5-dione