Abstract
We have explored a method to convert a muraymycin biosynthetic intermediate 3 to an anticancer drug lead 2 for in vivo and thorough preclinical studies. Cu(OAc)2 forms a stable complex with the amide 4 and prevents electrophilic reactions at the 2-((3-aminopropyl)amino)acetamide moiety. Under the present conditions, the desired 5″-primary amine was selectively protected with (Boc)2O to yield 6. The intermediate 6 was converted to 2 in two steps with 90% yield.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Benzamides / chemistry*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Humans
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Molecular Conformation
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N-Acetylglucosaminyltransferases / antagonists & inhibitors*
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N-Acetylglucosaminyltransferases / metabolism
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Nucleosides / chemistry*
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Nucleosides / metabolism
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Nucleotides / chemistry
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Peptides / chemistry
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Phenylurea Compounds / chemical synthesis*
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Phenylurea Compounds / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / pharmacology
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Structure-Activity Relationship
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Urea / chemistry
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Uridine / analogs & derivatives*
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Uridine / chemical synthesis
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Uridine / pharmacology
Substances
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1-(4-amidinophenyl)-3-(4-phenoxyphenyl)urea
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Antineoplastic Agents
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Benzamides
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Enzyme Inhibitors
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Nucleosides
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Nucleotides
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Peptides
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Phenylurea Compounds
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Piperidines
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aminouridyl phenoxypiperidinbenzyl urea
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muraymycin A1
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Urea
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N-Acetylglucosaminyltransferases
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dolichyl-phosphate alpha-N-acetylglucosaminyltransferase
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Uridine