N(2)-substituted D,L-cycloserine derivatives: synthesis and evaluation as alanine racemase inhibitors.
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.
Kim
Myoung Goo
MG
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Strych
Ulrich
U
Krause
Kurt
K
Benedik
Michael
M
Kohn
Harold
H
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
D000904:Antibiotics, Antitubercular; D004791:Enzyme Inhibitors; D003523:Cycloserine; D000411:Alanine Racemase