Tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

A disubstituted tropane derivative of general formula (Ia) or (Ib),

• 12
• or a pharmaceutically acceptable addition salt thereof or the N-oxide thereof, wherein
• R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, or 2-hydroxyethyl;
• R3 is
• CH2—X—R′,
• wherein X is O, S, or NR″;
• wherein R″ is hydrogen or alkyl;
• and
• R′ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, or —CO-alkyl;
• heteroaryl which may be substituted one or more times with
• alkyl, cycloalkyl, or cycloalkylalkyl;
• phenyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• phenylphenyl;
• pyridyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• thienyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• or
• benzyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• or
• (CH2)nCO2R11, COR11, or CH2R12;
• wherein R11 is
• alkyl, cycloalkyl, or cycloalkylalkyl;
• phenyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• phenylphenyl;
• pyridyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• thienyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• or
• benzyl;
• n is 0 or 1;
• and
• R12 is
• O-phenyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• or
• O—CO-phenyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, alkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl;
• R4is
• 3,4-methylenedioxyphenyl or
• phenyl, benzyl, naphthyl, or heteroaryl all of which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, and heteroaryl.