Recent Advances on Phosphodiesterase 4 Inhibitors for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease

Disposition, metabolism and mass balance of [14C]apremilast following oral administration

“…The minor metabolites M7 and M17 did retain some pharmacological activity but were present in circulation at concentrations that were generally <2% relative to apremilast and, therefore, are unlikely to contribute to the pharmacological activity of apremilast. These data are consistent with work that has been performed evaluating the structure-activity relationship of PDE4 inhibitors (Man et al 2009; Van der Mey et al 2001; Kodimuthali et al 2008). Based on these data, substitutions larger than a methoxy or ethoxy group at the 4-position of the phenyl ring lead to a significant reduction in PDE4 inhibition.…”

Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore

“…51 122 completed phase III trials with less than ideal results, leaving the drug's fate in question. Numerous analogs, particularly with more rigid scaffolds,123 have been developed to optimize activity and minimize nausea, diarrhea and headache symptoms associated with this class of inhibitors 124. A co-crystal structure with 51 bound in the phosphodiesterase reveals an interaction of the nitrile with methionine and leucine residues 125.…”

Zl-n-91, a selective phosphodiesterase 4 inhibitor, suppresses inflammatory response in a COPD-like rat model

“…Now COPD is still defined as a disease state characterized by poorly reversible airflow limitation induced by cigarette smoking and/or other noxious particle and gases, and spirometry is recommended to establish the diagnosis and the airflow limitation is usually progressive and associated with abnormal inflammatory response of the lungs to noxious particles or gases [30]. There had no drugs with special efficacy for COPD nowadays.…”