Benzofuran and quinoline carboxamides and quinoline sulfonamides as TNF inhibitors and as PDE4 inhibitors

Abstract

In these three patent applications, Chiroscience describes inhibitors of phosphodiesterase Type 4 (PDE4), an enzyme responsible for degrading levels of cAMP in cells. Increased levels of cellular cAMP limit the production of the proinflammatory cytokine TNFα. Therefore, agents that block the effects of PDE4 would maintain elevated cAMP levels and the synthesis of TNFα would be attenuated. This effect could have a beneficial impact on the treatment of inflammatory diseases such as arthritis and asthma. The compounds that are claimed have sought to replace the dialkoxyphenyl ring of rolipram-based inhibitors with other heterocycles in an effort to discover the optimum pharmacophore and lead to improved properties for this class of compounds.

• anti-inflammatory
• PDE4
• phosphodiesterase
• rolipram
• TNF-α