PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

Abstract

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents.

PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets

“…Due to its ability to regulate cAMP levels, the PDE4 enzyme subfamily could influence key processes involved in aneurysmal diseases, playing an important role in its development and emerging as a potential therapeutic target [63]. Interestingly, PDE4 is considered one of the main therapeutic targets in inflammatory diseases, owing to its critical role in controlling the rate of cAMP degradation in inflammatory and immune cells [64]. However, its relevance in aneurysmal diseases has been poorly explored.…”