Phenylpyrazolo[1,5-a]quinazolin-5(4H)-one: A Suitable Scaffold for the Development of Noncamptothecin Topoisomerase I (Top1) Inhibitors
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- 作者：Sabrina Taliani ; Isabella Pugliesi ; Elisabetta Barresi ; Silvia Salerno ; Christophe Marchand ; Keli Agama ; Francesca Simorini ; Concettina La Motta ; Anna Maria Marini ; Francesco Saverio Di Leva ; Luciana Marinelli ; Sandro Cosconati ; Ettore Novellino ; Yves Pommier ; Roberto Di Santo ; Federico Da Settimo
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：September 26, 2013
- 年：2013
- 卷：56
- 期：18
- 页码：7458-7462
- 全文大小：278K
- 年卷期：v.56,no.18(September 26, 2013)
- ISSN：1520-4804
文摘
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 Top1 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.