Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present)

ABSTRACT

Introduction: The cyclic nucleotides cAMP and cGMP are ubiquitous intracellular second messengers regulating a large variety of biological processes. The intracellular concentration of these biologically relevant molecules is modulated by the activity of phosphodiesterases (PDEs), a class of enzymes that is grouped in 11 families. The expression of PDEs is tissue- and cell-specific allowing spatiotemporal integration of multiple signaling cascades. PDE2A is a dual substrate enzyme and is expressed in both the periphery and in the central nervous system, however its expression is highest in the brain, where it is mainly localized in the cortex, hippocampus, and striatum. This suggests that this enzyme may regulate intraneuronal cGMP and cAMP levels in brain areas involved in emotion, perception, concentration, learning and memory.

Areas covered: This review covers the patent applications published between January 2010 and February 2016 on phosphodiesterase 2A inhibitors.

Expert opinion: Recent publications in the literature and in filed patent applications demonstrate the interest of pharmaceutical companies for PDE2A. This has increased the insights of its possible therapeutic role but the few clinical trials were terminated. Based on the ongoing interest in the field it is likely that new clinical trials can be expected and will unravel the therapeutic potential of PDE2A inhibition.

KEYWORDS:

• Phosphodiesterases
• phosphodiesterase 2A inhibitors
• PDE2A
• PDE10A

Article highlights

• Main biological processes and therapeutic applications of PDE2A inhibitors are described.

• A review of the patent literature and selected publications on PDE2A inhibitors over the past 5 years is provided.

• Most research groups have been pursuing selective PDE2A inhibitors, particularly for CNS related diseases.

• PDE2A activity, PDE selectivity profiles and in vivo studies, as described in patent applications, are reported.

• Clinical studies with novel selective and centrally active PDE2A inhibitors will help to unravel the therapeutic potential of PDE2A in CNS disorders.

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.