Compounds that are new 1,4-disubstituted piperidine derivatives pharmaceutical composition and processes for the treatment or prophylaxis of diseases associated with muscarinic receptors and for the preparation of 1,4-disubstituted piperidine derivatives containing fluorine

摘要

This invention relates to novel fluorine-containing 1,4-disubstituted piperidine derivatives represented by a general formula ÄIÜ CHEM and pharmaceutically acceptable salts thereof, Äwherein: Ar represents an aryl group or a hetero-aryl group having 1 to 2 hetero atoms selected from a group consisting of nitrogen, oxygen and sulfur (any 1 to 3 hydrogen atoms on the ring of said aryl or heteroaryl group may be substituted with lower alkyl, etc.); R1 represents C3-C6 cycloalkyl whose any 1-4 hydrogen atmos may be substituted with fluorine atoms(s); R2 represents C5-C15 saturated or unsaturated aliphatic hydrocarbon groups whose any 1 to 6 hydrogen atoms may be substituted with fluorine atom(s), aralkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl group having 1 to 2 hetero atoms selected from a group consisting of nitrogen, oxygen and sulfur (optionally any 1 to 3 hydrogen atoms on the ring in said aralkyl, arylalkenyl, hetero-arylalkyl or heteroarylalkenyl group may be substituted with lower alkyl, trifluoromethyl, cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy or amino, etc. ; and X stands for O or NH, provided that at least either one of R1 and R2 contains one or more fluorine atomsÜ. The compounds of the present invention have selective antagonistic activity for muscarinic M3 receptors, and exhibit excellent oral activity, duration of action and pharmacokinetics, so that they have little side effects and are safe and effective. Therefore they are useful for treatment or prophylaxis of respiratory diseases, urinary diseases and digestive diseases.