2. Academic Validation
  3. PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

  • Int J Mol Sci. 2023 Jul 15;24(14):11518. doi: 10.3390/ijms241411518.
Jian Jin 1,  Francesca Mazzacuva 2,  Letizia Crocetti 3,  Maria Paola Giovannoni 3,  Agostino Cilibrizzi 1 4
Affiliations

Affiliations

  • 1 Institute of Pharmaceutical Science, King's College London, Stamford Street, London SE1 9NH, UK.
  • 2 School of Health, Sport and Bioscience, University of East London, London E15 4LZ, UK.
  • 3 Neurofarba Department, Pharmaceutical and Nutraceutical Section, Via Ugo Schiff 6, Sesto Fiorentino, University of Florence, 50019 Florence, Italy.
  • 4 Centre for Therapeutic Innovation, University of Bath, Bath BA2 7AY, UK.
PMID: 37511275 DOI: 10.3390/ijms241411518
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.

Keywords

PDE4 inhibitors; PDE4 selectivity; dual activity; phosphodiesterases 4; respiratory diseases; structural analysis.

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