ABSTRACT
Phosphodiesterase-4 inhibitors (PDE4) are of great interest for the treatment of airway inflammatory diseases due to its broad anti-inflammatory effects. Roflumilast is a selective PDE4 inhibitor that inhibits pulmonary and systemic inflammation and rallies symptoms in airway diseases. Asthma and COPD are common chronic airway inflammatory diseases having incompletely illustrious pathophysiology and clinical manifestations. Recently, the condition called Asthma- COPD Overlap (ACO) has been evolved having the overlapping symptoms of both diseases. The newly discovered PDE4 inhibitor, roflumilast has exposed its potential in the treatment of Asthma, COPD and ACOS. Its mechanism of action in airway inflammatory diseases are said to be exerts by elevating intracellular cAMP and shows its anti-inflammatory action. Roflumilast, a promising therapeutic approach in inflammatory airway diseases, has many significant outcomes. In this review, we have provided various promising clinical evidences of roflumilast in COPD and asthma. However, there is no published clinical evidence to date for the role of roflumilast in ACOS. Nevertheless, there are therapeutic mechanisms that provide a reference for clinical application for ACOS.
Subject(s)
Aminopyridines/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Benzamides/therapeutic use , Phosphodiesterase 4 Inhibitors/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Animals , Asthma/metabolism , Asthma/physiopathology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cyclopropanes/therapeutic use , Humans , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory System/metabolism , Treatment OutcomeABSTRACT
BACKGROUND: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. METHODS: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. RESULTS: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. CONCLUSION: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.
