Novel 1-Aryl-3-Azabicyclo[3.1.0]Hexanes: Preparation And Use To Treat Neuropsychiatric Disorders

1 - 93 . (canceled)

94 . A compound of the following formula II:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are independently selected from hydrogen, unsubstituted C 1-10 alkyl, C 3-10 alkenyl and C 3-10 alkynyl, and substituted C 1-10 alkyl, C 3-10 alkenyl and C 3-10 alkynyl wherein the substituent is one or more of hydroxy, cyano, halogen, C 1-6 alkoxy, aryl substituted C 1-6 alkoxy, aryloxy, aryloxy substituted with one or more halogens, C 1-6 alkyl, C 1-6 alkyl independently substituted with one or more of cyano and halogen, C 1-4 alkoxy, and C 1-4 haloalkoxy;

R 3 is selected from hydrogen, C 1-6 alkoxycarbonyl, C 2-6 alkanoyl, C 3-8 cycloalkyl, C 4-9 cycloalkanoyl, aryl, heteroaryl, saturated heterocyclic, C 2-10 alkenyl, C 2-10 alkynyl, and substituted C 1-6 alkyl, C 2-10 alkenyl and C 2-10 alkynyl wherein the substituent is one or more of cyano, halogen, hydroxy, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 2-6 alkyloxycarbonyloxy, C 1-6 alkanoyl, C 1-6 alkanoyloxy, C 3-8 cycloalkyl, C 3-8 cycloalkyloxy, C 4-9 cycloalkanoyl, aryl, aryloxy, heteroaryl and saturated heterocyclic; and

R 4 and R 5 are independently hydrogen or 1-4 substituents independently selected from halogen, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo(C 1-3 )alkyl, cyano, hydroxy, C 3-5 cycloalkyl, C 1-3 alkoxy, C 1-3 alkoxy(C 1-3 )alkyl, carboxy(C 1-3 )alkyl, C 1-3 alkanoyl, halo(C 1-3 )alkoxy, nitro, amino, C 1-3 alkylamino, and di(C 1-3 )alkylamino.

95 . A compound of the following formula III:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are independently selected from hydrogen, unsubstituted C 1-10 alkyl, C 3-10 alkenyl and C 3-10 alkynyl, and substituted C 1-10 alkyl, C 3-10 alkenyl and C 3-10 alkynyl wherein the substituent is one or more of hydroxy, cyano, halogen, C 1-6 alkoxy, aryl substituted C 1-6 alkoxy, aryloxy, aryloxy substituted with one or more halogens, C 1-6 alkyl, C 1-6 alkyl independently substituted with one or more of cyano and halogen, C 1-4 alkoxy, and C 1-4 haloalkoxy;

R 3 is selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxycarbonyl, C 2-6 alkanoyl, C 3-8 cycloalkyl, C 4-9 cycloalkanoyl, aryl, heteroaryl, saturated heterocyclic, C 2-10 alkenyl, C 2-10 alkynyl, and substituted C 1-6 alkyl, C 2-10 alkenyl and C 2-10 alkynyl wherein the substituent is one or more of cyano, halogen, hydroxy, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 2-6 alkyloxycarbonyloxy, C 1-6 alkanoyl, C 1-6 alkanoyloxy, C 3-8 cycloalkyl, C 3-8 cycloalkyloxy, C 4-9 cycloalkanoyl, aryl, aryloxy, heteroaryl and saturated heterocyclic; and

R 4 and R 5 are independently hydrogen or 1-4 substituents independently selected from halogen, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo(C 1-3 )alkyl, cyano, hydroxy, C 3-5 cycloalkyl, C 1-3 alkoxy, C 1-3 alkoxy(C 1-3 )alkyl, carboxy(C 1-3 )alkyl, C 1-3 alkanoyl, halo(C 1-3 )alkoxy, nitro, amino, C 1-3 alkylamino, and di(C 1-3 )alkylamino.

96 . The compound according to claim 95 , wherein R 4 and R 5 are independently hydrogen or 1-4 substituents independently selected from methyl, ethyl, propyl, fluoro, chloro, trifluoromethyl, cyano, nitro, methoxy, ethoxy and trifluoromethoxy.

97 . The compound according to claim 96 , wherein R 1 and R 2 are hydrogen, R 3 is hydrogen, methyl, ethyl or isopropyl and R 4 and R 5 are independently selected from hydrogen, methyl, chloro, fluoro, propyl, methoxy and ethoxy.

98 . The compound according to claim 97 , wherein the compound is:

1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane;

3-methyl-1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane;

1-(1-fluoronaphthalen-4-yl)-3-aza-bicyclo[3.1.0]hexane;

1-(1-fluoronaphthalen-4-yl)-3-methyl-3-aza-bicyclo[3.1.0]hexane;

1-(1-methylnaphthalen-4-yl)-3-aza-bicyclo[3.1.0]hexane; or

3-methyl-1-(1-methylnaphthalen-4-yl)-3-aza-bicyclo[3.1.0]hexane;

or a pharmaceutically acceptable salt thereof.

99 . The compound according to claim 98 , wherein the compound is:

(1R,5 S)-1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane;

(1S,5R)-1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane;

(1R,5S)-3-methyl-1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane; or

(1S,5R)-3-methyl-1-(naphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane;

or a pharmaceutically acceptable salt thereof.

100 . A pharmaceutical composition, wherein the pharmaceutical composition comprises a compound or pharmaceutically acceptable salt thereof according to claim 98 and a pharmaceutically acceptable carrier or vehicle therefor.

101 . A method for treating a central nervous system (CNS) disorder in a mammalian subject in need thereof, wherein the method comprises administering to the mammalian subject an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 98 .

102 . The method according to claim 101 , wherein the CNS disorder is depression.

103 . The method according to claim 101 , wherein the CNS disorder is an anxiety disorder.

104 . The method according to claim 101 , wherein the CNS disorder is attention deficit hyperactivity disorder (ADHD).