Aralkyl diazabicycloalkane derivatives for CNS disorders

A compound of the formula:

• wherein each of R1, R4, and R5 is independently selected from the group consisting of hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxyalkyl, haloalkyl, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• wherein R6 and R7 are hydrogen;
• wherein each of R2, R3, R8, R9, and R11 through R13 is independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• wherein R10 is selected from the group consisting of hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, haloalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;wherein R2 and R3 may be taken together to form oxo or may be taken together with the carbon to which they are attached to form a saturated or partially unsaturated carbocyclic group having three to eight ring carbons;
• wherein R4 and R5 may be taken together to form oxo or may be taken together with the carbon to which they are attached to form a saturated or partially unsaturated carbocyclic group having three to eight ring carbons;
• wherein R8 and R9 may be taken together to form oxo;
• wherein R10 and R11 may be taken together to form oxo;
• wherein m is equal to one;
• wherein Z is selected from the group consisting of
• wherein each of R15 and R16 is independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aralkoxy, aryloxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, halo, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl and alkanoyl;
• wherein each of R17 and R18 is independently selected from the group consisting of hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, haloalkyl, hydroxyalkyl, halo, cyano, carboxy, carboxyalkyl and alkanoyl;
• wherein when Z is
• n and p are one or two, with a sum of two or three, and when Z is
• n and p are each one;
• wherein A is selected from the group consisting of aryl, heteroaryl, aryloxy, heteroaryloxy, aralkoxy, heteroaralkoxy, arylamino, heteroarylamino, aralkylamino, heteroaralkylamino, arylthio, heteroarylthio, aralkylthio, and heteroaralkylthio;
• wherein A can be further substituted with one or more substituents independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, halo, haloalkyl, hydroxyalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that when n and p both are 1, R4 and R5 are not alkyl, and at least one of R4 and R5 is not hydrogen.

A pharmaceutical composition comprising:

• (a) a compound of the formula:
• wherein each of R1, R41 and R5 is independently selected from the group consisting of hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxyalkyl, haloalkyl, hydroxyalkyl, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• wherein R6 and R7 are hydrogen;
• wherein each of R2, R3, and R8 through R13 is independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• wherein R2 and R3 may be taken together to form oxo or may be taken together with the carbon to which they are attached to form a saturated or partially unsaturated carbocyclic group having three to eight ring carbons;
• wherein R4 and R5 may be taken together to form oxo or may be taken together with the carbon to which they are attached to form a saturated or partially unsaturated carbocyclic group having three to eight ring carbons;
• wherein R8 and R9 may be taken together to form oxo;
• wherein R10 and R11 may be taken together to form oxo;
• wherein m is equal to one;
• wherein Z is selected from the group consisting of
• wherein each of R15 and R16 is independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aralkoxy, aryloxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, halo, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl and alkanoyl;
• wherein each of R17 and R18 is independently selected from the group consisting of hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, haloalkyl, hydroxyalkyl, halo, cyano, carboxy, carboxyalkyl and alkanoyl;
• wherein when Z is
• n and p are one or two, with a sum of two or three, and when Z is
• n and p are each one;
• wherein A is selected from the group consisting of aryl, heteroaryl, aryloxy, heteroaryloxy, aralkoxy, heteroaralkoxy, arylamino, heteroarylamino, aralkylamino, heteroaralkylamino, arylthio, heteroarylthio, aralkylthio, and heteroaralkylthio;
• wherein A can be further substituted with one or more substituents independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, halo, haloalkyl, hydroxyalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl, and alkynyl;
• or a pharmaceutically acceptable salt thereof in an amount that is therapeutically-effective for treating or preventing a CNS-related disorder selected from the group consisting of ischemia and psychotic disorders, and
• (b) a pharmaceutically-acceptable carrier or diluent.