Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jan 15;26(2):454-459.
doi: 10.1016/j.bmcl.2015.11.093. Epub 2015 Nov 26.

Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors

Jacques Le Roux  1 , Caroline Leriche  2 , Philippe Chamiot-Clerc  2 , John Feutrill  3 , Frank Halley  4 , David Papin  1 , Nathalie Derimay  5 , Christelle Mugler  5 , Claudine Grépin  2 , Laurent Schio  1
Affiliations

Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors

Jacques Le Roux et al. Bioorg Med Chem Lett. .

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.

Keywords: Carboxamide; PDE4 inhibitor; cAMP.

PubMed Disclaimer

MeSH terms

Substances

LinkOut - more resources