The present invention relates to novel compounds which are both phosphodiesterase 4 (PDE 4) enzyme inhibitors and muscarinic M 3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic uses thereof. Binding assay: CHO-K1 clone cells expressing the human M3 receptor (Swissprot P 20309) were incubated with Ca++/ Mg++Free phosphate buffered saline and harvested by centrifugation at 1500 rpm for 3 minutes. The pellet was resuspended in ice-cold buffer A (15 mM Tris-HCl pH 7.4, 2 mM MgCl2, 0.3 mM EDTA, 1 mM EGTA) and homogenized with a PBI polytron (set at 5 for 15 seconds). The crude membrane fraction was recovered by two successive centrifugation steps of 40000 g at 4 C. for 20 minutes and separated by a washing step in buffer A. Finally, the obtained pellet was resuspended in buffer B (75 mM Tris HCl pH 7.4, 12.5 mM MgCl2, 0.3 mM EDTA, 1 mM EGTA, 250 mM sucrose) and aliquots were stored at-80 C. On the day of the experiment, frozen membranes were washed with buffer C (50 mM Tris-HCl pH 7.4, 2.5 mM MgCl2, 1 mM EDTA). Nonselective muscarinic radioligand [3H]-N-methyl scopolamine (Mol. Pharmacol. 45: 899-907) was used to label the M3 binding site. Binding experiments were performed in duplicate at radioactive ligand concentrations of 0.1 to 0.3 nM in 96 well plates (10 point concentration curve). Nonspecific binding was determined in the presence of 10 M cold N-methyl scopolamine. Samples (final volume 0.75 mL) were incubated at room temperature for 90 minutes. The reaction was terminated by rapid filtration through a GF / B uni filter plate and two washes (0.75 mL) with cold buffer C using Packard Filtermate Harvester. The radioactivity on the filter was measured with a microplate scintillation counter TriCarb 2500 (PerkinElmer). Representative compounds of the present invention, when tested with one of the above reported protocols, show ICs lower than 100 nM50showed that. Representative compounds of the invention are IC
