89977-62-8Relevant academic research and scientific papers
Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors
Le Roux, Jacques,Leriche, Caroline,Chamiot-Clerc, Philippe,Feutrill, John,Halley, Frank,Papin, David,Derimay, Nathalie,Mugler, Christelle,Grépin, Claudine,Schio, Laurent
, p. 454 - 459 (2016)
A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50 = 165 nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50 = 0.7 nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency.
