New methods for the discovery and synthesis of PDE7 inhibitors as new drugs for neurological and inflammatory disorders

Abstract

Introduction: Phosphodiesterase 7 (PDE7) is a high-affinity cyclic AMP (cAMP)-specific PDE that is expressed in immune and proinflammatory cells. The PDE7 recently emerged a pharmacological target in the context of the immune and neurological responses to alleviate chronic inflammation and neurodegenerative disorders.

Areas covered: This review explains PDE7 as a therapeutic target for neurological and inflammation disorders. Additionally, specification of PDE7 inhibitors, functional diversity between PDE7A and 7B, inhibitor selectivity to PDE7 isoforms, and new discovery methods for PDE7 inhibitors such as synthesis, quantitative structure activity relationship (QSAR) studies, ligand-based virtual screening, and structure-based screening (docking) are discussed.

Expert opinion: There are only a few selective PDE7 inhibitors that can discriminate between PDE7A and PDE7B, but due to different tissue distribution and physiological functions in the body, the hope is to develop selective PDE7A and PDE7B inhibitors to target more specific functions and pathological conditions without a high likelihood of causing nonspecific side effects. Conventional approaches such as synthesis and QSARs are currently used to find specific PDE7 inhibitors. The development of computational-based screening of databases has provided many opportunities to discover new ligands based on biological activity in a very short period.

Keywords::

• drug discovery
• inflammatory disorders
• neurological disorders
• metabolism
• phosphodiesterase inhibitors
• review
• toxicology

Notes

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