title: N(2)-substituted D,L-cycloserine derivatives: synthesis and evaluation as alanine racemase inhibitors.
abstract: A select series of N(2)-substituted D,L-cycloserine derivatives were prepared a ndevaluated for inhibitory activity against purified alanine racemases (alr gene product) from Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis, as well as in a growth inhibition assay. N(2)-Modification led to loss of enzymatic inhibitory activity in most cases consistent with a recent proposal for cycloserine function.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
authors.forename: Myoung Goo
authors.initials: MG
authors.lastname: Kim
authors.forename: Ulrich
authors.initials: U
authors.lastname: Strych
authors.forename: Kurt
authors.initials: K
authors.lastname: Krause
authors.forename: Michael
authors.initials: M
authors.lastname: Benedik
authors.forename: Harold
authors.initials: H
authors.lastname: Kohn
mesh_terms: D000411:Alanine Racemase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000904:Antibiotics, Antitubercular / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003523:Cycloserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology; D019906:Nuclear Magnetic Resonance, Biomolecular; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000904:Antibiotics, Antitubercular; D004791:Enzyme Inhibitors; D003523:Cycloserine; D000411:Alanine Racemase