Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 18, Pages 7458-7462Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm400932c
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- University of Pisa
- Sapienza University of Rome
- Center for Cancer Research, Intramural Program of the NCI, NIH
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In search for a novel chemotype to develop topoisomerase I (Top1) inhibitors, the pyrazolo[1,5-a]quinazoline nucleus, structurally related to the indenoisoquinoline system precursor of well-known Top I poisons, was variously decorated (i.e., a substituted phenyl ring at 2- or 3-position, a protonable side chain at 4- or 5-position), affording a number of Top1 inhibitors with cleavage patterns common to CPT and MJ-III-65. SARs data were rationalized by means of an advanced docking protocol.
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