Phenylpyrazolo[1,5-a]quinazolin-5(4H)-one: A Suitable Scaffold for the Development of Noncamptothecin Topoisomerase I (Top1) Inhibitors

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 protocol.

Pyrazolo[1,5-a]quinazoline scaffold as 5-deaza analogue of pyrazolo[5,1-c][1,2,4]benzotriazine system: synthesis of new derivatives, biological activity on GABAA receptor subtype and molecular dynamic study

“…The desired tosyl derivatives (1a 0 , 1c 0 , and 1d 0 ) were obtained in good yield and pure enough for the next reaction by the simple treatment of the lactam (1a, 1c, and 1d) with tosyl chloride in DCM, in the presence of NEt 3 . These intermediates were reacted in anhydrous DMF, t-BuOK, and benzyl alcohol to give the desired 5-benzyloxyderivatives (4)(5)(6).…”

Substrate‐Controlled [5+1] Annulation of 5‐Amino‐1H‐phenylpyrazoles with Alkenes: Divergent Synthesis of Multisubstituted 4,5‐Dihydropyrazolo[1,5‐a]quinazolines

“…However, efficient synthetic approach to obtain 4,5‐dihydropyrazolo[1,5‐ a ]quinazolines is rather difficult to achieve. To the best of our knowledge, the only feasible method is the direct reduction of pyrazolo[1,5‐ a ]quinazolines, which could only be constructed through multistep transformation under the assist of metal reductant (Scheme a) . In addition, functionalization at the 5‐position of resultant 4,5‐dihydropyrazolo[1,5‐ a ]quinazolines could not be accomplished.…”

Pyrazoloquinazolines: Synthetic strategies and bioactivities

“…Taliani et al disclosed the topoisomerase-1 inhibitory activity [99] of phenylpyrazolo[1,5-a]quinazoline-5(4H)-one [100]. From SAR studies ( Figure 24) it has been revealed that the topoisomerase-1 inhibitory activity can be increased by substituting 3-phenyl ring.…”