Abstract
A series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after i.v. administration.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Line, Tumor
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Humans
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Polo-Like Kinase 1
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Quinazolines / chemistry*
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Quinazolines / pharmacology*
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Structure-Activity Relationship
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Transplantation, Heterologous
Substances
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Cell Cycle Proteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Quinazolines
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Protein Serine-Threonine Kinases