56709-97-8Relevant articles and documents
The identification of the 2-phenylphthalazin-1(2 H)-one scaffold as a new decorable core skeleton for the design of potent and selective human A 3 adenosine receptor antagonists
Poli, Daniela,Catarzi, Daniela,Colotta, Vittoria,Varano, Flavia,Filacchioni, Guido,Daniele, Simona,Trincavelli, Letizia,Martini, Claudia,Paoletta, Silvia,Moro, Stefano
, p. 2102 - 2113 (2011/06/17)
Following a molecular simplification approach, we have identified the 2-phenylphthalazin-1(2H)-one (PHTZ) ring system as a new decorable core skeleton for the design of novel hA3 adenosine receptor (AR) antagonists. Interest for this new series was driven by the structural similarity between the PHTZ skeleton and both the 2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (TQX) and the 4-carboxamido-quinazoline (QZ) scaffolds extensively investigated in our previously reported studies. Our attention was focused at position 4 of the phthalazine nucleus where different amido and ureido moieties were introduced (compounds 2-20). Some of the new PHTZ compounds showed high hA3 AR affinity and selectivity, the 2,5-dimethoxyphenylphthalazin-1(2H)-one 18 being the most potent and selective hA3 AR antagonist among this series (Ki = 0.776 nM; hA1/hA3 and hA 2A/hA3 > 12000). Molecular docking studies on the PHTZ derivatives revealed for these compounds a binding mode similar to that of the previously reported TQX and QZ series, as was expected from the simplification approach.
