Heteroaryl diazabicycloalkanes, their preparation and use

A diazabicycloalkane derivative represented by Formula 1

• any of its enantiomers or any mixture thereof, an N oxide thereof, a pharmaceutically acceptable salt thereof, wherein,
• n is 2 or 3;
• and
• m is 1, 2 or 3;
• and
• one of R and R1 represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, or aralkyl;
• and
• the other of R and R1 represents a monocyclic 5 to 6 membered heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen,
• which monocyclic heterocyclic group may be substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, hydroxyalkoxy, alkoxycycloalkyl, cycloalkoxy, cycloalkoxyalkoxy, alkenyl, alkenoxy, alkoxyalkenyl, alkynyl, alkynoxy, alkoxyalkynyl, alkylthio, alkenylthio, alkynylthio, alkylseleno, alkenylseleno, alkynylseleno, methylenedioxy, trifluoromethanesulfonyloxy, halogen, —OH, —CF3, —OCF3, —CN, amino, nitro, oxime, or a group of the formula —COOR3, —CONR2R3, —NH—CO2R2, —NHCO—R2, —OCO—NR2R3;
• in which formulae R2 and R3 independently of each another represents hydrogen or alkyl;
• or
• which monocyclic heterocyclic group may be substituted with an aryl group, which aryl group is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino or nitro;
• or
• which monocyclic heterocyclic group may be substituted with a group of the formula “—X-alkyl-Y-alkyl”, wherein X and Y independently of each another represents O (epoxy), S, NH, N-alkyl or Se, and the alkyl group is optionally substituted with alkoxy, or thioalkoxy;
• or
• which monocyclic heterocyclic group may be substituted with a group of the formula “—X-(ALK)o-aryl”, wherein X represents O, S, NH, N-alkyl or Se;
• “ALK” represents alkyl, alkenyl or alkynyl;
• o is 0 or 1;
• and aryl is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino or nitro oxime;
• or
• which monocyclic heterocyclic group may be substituted with a group of the formula “—X-(ALK)o-Z”, wherein X represents O, S, NH, N-alkyl or Se;
• “ALK” represents alkyl, alkenyl or alkynyl;
• o is 0 or 1;
• and Z represents a 5- or 6-membered monocyclic heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, which group is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino, nitro or oxime;
• or
• which monocyclic heterocyclic group may be substituted with another monocyclic 5 to 6 membered heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, which additional heterocyclic group is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino, nitro or oxime;
• or
• which monocyclic heterocyclic group may be substituted with a group of the formula “(ALK)o-HET”, wherein “ALK” represents alkyl, alkenyl or alkynyl;
• o is 0 or 1;
• and “HET” represents a 3- to 8-membered non-aromatic heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen;
• or
• the other of R and R1 represents a bicyclic heterocyclic group, composed of a 5 to 6 membered monocyclic heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen fused to a benzene ring, and
• which bicyclic heterocyclic group may be substituted one or more times with
• alkyl;
• cycloalkyl;
• cycloalkylalkyl;
• alkenyl;
• alkynyl;
• alkoxy;
• alkoxy-alkoxy;
• cycloalkoxy;
• alkenoxy;
• alkynoxy;
• methylenedioxy;
• halogen;
• —OH;
• —CF3;
• —OCF3;
• —CN;
• amino;
• nitro or oxime;
• an aryl group, which aryl group is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino or nitro;
• a monocyclic 5- to 6-membered heterocyclic group containing one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, which heterocyclic group is optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, —OH, —CF3, —OCF3, —CN, amino, nitro or oxime;
• or
• R and/or R1, together with the nitrogen atom to which they are attached, represent an alkyl-onium salt, a dialkyl-onium salt, a cycloalkyl-onium salt, an alkyl-cycloalkyl-onium salt, a dicycloalkyl-onium salt, an alkyl-cycloalkylalkyl-onium salt, a cycloalkyl-cycloalkylalkyl-onium salt, or a dicycloalkylalkyl-onium salt.