Abstract
A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology*
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Biological Availability
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Drug Screening Assays, Antitumor
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Humans
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Indoles / chemical synthesis*
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Indoles / pharmacokinetics
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Indoles / pharmacology*
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Mice
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Microtubules / drug effects
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Microtubules / metabolism
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Models, Molecular
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Oxazoles / chemical synthesis*
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Oxazoles / pharmacokinetics
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Oxazoles / pharmacology*
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Polymers / chemical synthesis
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Rats
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Stereoisomerism
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Tubulin / metabolism*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Indoles
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Oxazoles
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Polymers
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Tubulin
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A 289099