Internal medicine

Receptor

Enzyme

Nucleotide

Phosphodiesterase

Gene

Chemistry

Cyclic adenosine monophosphate

Cyclic nucleotide phosphodiesterase

Cyclic nucleotide

Pulmonary disease

Biochemistry

Pharmacophore

Medicine

Pharmacology

Journal of Medicinal Chemistry

Cyclic nucleotide phosphodiesterase 4 (PDE4) specifically hydrolyzes cyclic adenosine monophosphate (cAMP) and plays vital roles in biological processes such as cancer development. To date, PDE4 inhibitors have been widely studied as therapeutics for the treatment of various diseases such as chronic obstructive pulmonary disease, and many of them have progressed to clinical trials or have been approved as drugs. Herein, we review the advances in the development of PDE4 inhibitors in the past decade and will focus on their pharmacophores, PDE4 subfamily selectivity, and therapeutic potential. Hopefully, this analysis will lead to a strategy for development of novel therapeutics targeting PDE4.

Advances in the Development of Phosphodiesterase-4 Inhibitors