pha-408 and Asthma

Installation of sites for metabolism in the lead compound PHA-767408 was the key focus of the IKK-2 inhaled program. This paper reports our efforts to identify a novel series of aminopyridinecarboxamide-based IKK-2 inhibitors, which display low nanomolar potency against IKK-2 with long duration of action (DOA), and metabolically labile to phase I and/or phase II metabolizing enzymes with potential capability for multiple routes of clearance. Several compounds have demonstrated their potential usefulness in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

Topics: Administration, Inhalation; Aminopyridines; Asthma; Binding, Competitive; Drug Design; HEK293 Cells; Humans; I-kappa B Kinase; Indazoles; Isonicotinic Acids; Microsomes, Liver; Models, Molecular; Molecular Structure; Molecular Targeted Therapy; Niacinamide; Phenethylamines; Potassium Channel Blockers; Protein Kinase Inhibitors; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Structure-Activity Relationship; Sulfonamides