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
Phenylpyrazolo[1,5‑a]quinazolin-5(4H)‑one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors / S., Taliani; I., Pugliesi; E., Barresi; S., Salerno; C., Marchand; K., Agama; F., Simorini; C., La Motta; A. M., Marini; F. S., Di Leva; L., Marinelli; S., Cosconati; E., Novellino; Y., Pommier; DI SANTO, Roberto; F., Da Settimo. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 56:(2013), pp. 7458-7462. [10.1021/jm400932c]
Phenylpyrazolo[1,5‑a]quinazolin-5(4H)‑one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors
DI SANTO, Roberto;
2013
Abstract
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 protocolI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
