Phosphodiesterase‑4 inhibitors: a review of current developments (2013-2021).

Introduction: Cyclic nucleotide phosphodiesterase 4 (PDE4) is responsible for the hydrolysis of cAMP, which has become an attractive therapeutic target for lung, skin, and severe neurological diseases. Here, we review the current status of development of PDE4 inhibitors since 2013 and discuss the applicability of novel medicinal-chemistry strategies for identifying more efficient and safer inhibitors.

Areas Covered: This review summarizes the clinical development of PDE4 inhibitors from 2013 to 2021, focused on their pharmacophores, the strategies to reduce the side effects of PDE4 inhibitors and the development of subfamily selective PDE4 inhibitors.

Discovery and optimization of new 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives as potent influenza virus PA inhibitors.

Annual unpredictable efficacy of vaccines, coupled with emerging drug resistance, underlines the development of new antiviral drugs to treat influenza infections. The N-terminal domain of the PA (PA) endonuclease is both highly conserved across influenza strains and serotypes and is indispensable for the viral lifecycle, making it an attractive target for new antiviral therapies. Here, we describe the discovery of a new class of PA inhibitors derived from recently identified, highly active hits for PA endonuclease inhibition.