Aminoester derivatives

• Main Authors: AMARI GABRIELE, CAPALDI CARMELIDA, VAN DE POEL HERVE, LINNEY IAN, BAKER-GLENN CHARLES, ARMANI ELISABETTA, TRIVEDI NAIMISHA, BLACKABY WESLEY
• Format: Patent
• Language: Chinese; English
• Published: 22.02.2017
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention relates to novel compounds which are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof. M3 Binging assay: CHO-KI clone cells expressing the human M3- receptor (Swissprot P20309) were harvested in Ca++/Mg++free phosphate-buffered saline and collected by centrifugation at 1500 rpm for 3 min. The pellets were resuspended in ice cold buffer A (15 mM Tris-HCI pH 7.4, 2 mM MgCI2, 0.3 mM EDTA, 1 mM EGTA) and homogenized by a PBI politron (setting 5 for 15 s). The crude membrane fraction was collected by two consecutive centrifugation steps at 40000 g for 20 min at 4 degrees, separated by a washing step in buffer A. The pellets obtained were finally resuspended in buffer B (75 mM Tris HCI pH 7.4, 12.5mM MgCI2, 0.3 mM EDTA, 1 mM EGTA, 250 mM sucrose), and aliquots were stored at - 80 degrees. The day of experiment, frozen membranes were resuspended in buffer C (50 mM Tris-