1,4-diazabicycloalkane derivatives, their preparation and use
View Patent ↗This invention relates to novel 1,4-diazabicycloalkane derivatives and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.
1. A 1,4-diazabicycloalkane compound of Formula IV:
any of its enantiomers or any mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof, or an N-oxide thereof, wherein Ar represents an aryl group selected from phenyl and naphthyl, or a heteroaryl group selected from furanyl, thienyl and pyridinyl, which aromatic group may optionally be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, alkynyl, alkoxy, alkoxy-alkyl, alkoxy-alkoxy, cycloalkoxy, cycloalkoxy-alkyl, cycloalkoxy-alkoxy, halogen, CF 3 , CN, NO 2 , NH 2 , carboxy, carbamoyl, amido, sulfamoyl, phenyl and benzyl.
2. The compound of claim 1 , wherein Ar may optionally be substituted one or more times with substituents selected from the group consisting of alkyl, alkoxy, halogen, CF 3 , CN, NO 2 , NH 2 and phenyl.
3. The compound of claim 1 , wherein Ar represents phenyl, optionally substituted one or two times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkoxy, cycloalleoxy, halogen, CF 3 , CN, NO 2 , NH 2 carboxy, carbamoyl, amido and sulfamoyl.
4. The compound of claim 1 , which is
4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-1,4-diazabicyclo[3 .2.2]nonane;
4-[5-(3-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
4-[5-(4-Merhoxyphenyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
4-[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3 .2.2]nonane;
4-[5-(4-Phenyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
4-[5-(2-Naphthyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
4-[5-(2-Furyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
4-[5-(3-Pyridyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonaue;
4-[5-(4-Pyridyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane; or
4-[5-(2-Tbienyl)-1,3,4-oxadiazol-2-yl]-1,4-diazabicyclo[3.2.2]nonane;
or an enantiomer or a mixture of enantiomers, or a pharmaceutically-acceptable addition salt thereot or an N-oxide thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , any of its enantiomers or any mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof, together with at least one pharmaceutically-acceptable carrier or diluent.
6. A method of the treatment or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disease or disorder is associated with withdrawal symptoms caused by termination of use of tobacco, heroin, cocaine, morphine, benzodiazepines, beuzodiazepine-like drugs, or alcohol, which method comprises the step of administering to such a living animal body, including a human, in need thereof a therapeutically effective amount of a compound of claim 1 , any of its enantiomers or any mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof.
7. The 1,4-diazabicycloalkane compound of clalm 1 , wherein Ar represents phenyl, optionally substituted one or two times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkoxy, cycloalkoxy, halogen, CF 3 , CN, NO 2 , NH 2 , carboxy, carbamoyl, amido, sulfamoyl, phenyl, and benzyl.
8. The 1,4-diazabicycloalkane compound of claim 7 , wherein Ar represents phenyl, optionally substituted one or two times with substituents selected fiom the group consisting of alkyl, alkoxy, halogen, CF 3 , CN, NO 2 , NH 2 , and phenyl.