Abstract
In a high-throughput screening effort, a series of tetrahydroisoquinolines was identified as modest inhibitors of human Eg5. A medicinal chemistry optimization effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4-dihydroisoquinoline-2(1H)-carboxamide (32a) as a potent inhibitor of human Eg5 (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50 234 nM).
MeSH terms
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Adenosine Triphosphatases / antagonists & inhibitors
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Drug Screening Assays, Antitumor
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Humans
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Inhibitory Concentration 50
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Isoquinolines / chemical synthesis*
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Isoquinolines / pharmacology
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Kinesins / antagonists & inhibitors*
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Mitosis / drug effects*
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Molecular Structure
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Tetrahydroisoquinolines / chemical synthesis
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Tetrahydroisoquinolines / pharmacology*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Isoquinolines
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N-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
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Tetrahydroisoquinolines
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Adenosine Triphosphatases
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Kinesins