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Updated: Mar 28, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors
Jacques Le Roux1, Caroline Leriche2, Philippe Chamiot-Clerc2
1Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.
Abstract:
A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). 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.
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