CYCLOPENTA[b][1,4]DIAZEPINO[6,7,1-hi]INDOLES AND DERIVATIVES

Abstract

This invention provides compounds of the formulae: wherein: R 1 is hydrogen, —C(O)CH 3 or alkyl of 1-6 carbon atoms; R 2 and R 3 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl, alkoxy of 1-6 carbon atoms, —CH 2 OH, fluoroalkyl, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluoroalkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, aryl, or aroyl; R 4 and R 5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluoroalkyl, —CN, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluoroalkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, or aroyl; R 6 and R 7 are each independently hydrogen, C 1 -C 6 alkyl or cycloalkyl; or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions containing these compounds and methods for their use, including treatment of obsessive-compulsive disorder, panic disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, migraine, sleep disorders, eating disorders, obesity, epilepsy, and spinal cord injury.

1 .- 5 . (canceled)  
   
   
       6 . A method of treating in a mammal a condition selected from behavioral disorders associated with dementia or age-related conditions- and aggressivity, the method comprising administering to a mammal a pharmaceutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is hydrogen, —C(O)CH 3  or alkyl of 1-6 carbon atoms;  
 R 2  and R 3  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl, alkoxy of 1-6 carbon atoms, —CH 2 OH, fluorinated alkyl of 1-6 carbon atoms, —NH—SO 2 -alkyl of 1-6 carbon atoms, —SO 2 —NH-alkyl of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluorinated alkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, aryl, or aroyl;  
 R 4  and R 5  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluorinated alkyl of 1-6 carbon atoms, —CN, —NH—SO 2 -alkyl of 1-6 carbon atoms, —SO 2 —NH-alkyl of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluorinated alkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, or aroyl;  
 R 6  and R 7  are each independently hydrogen, C 1 -C 6  alkyl, cycloalkyl of 3 to 7 carbon atoms or —CH 2 -(cycloalkyl of 3 to 7 carbon atoms);  
 the dashed line indicates an optional double bond.  
 
   
   
       7 . The method of  claim 6  wherein the mammal is a human.  
   
   
       8 . The method of  claim 7  wherein the compound administered is at least one compound selected from  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is hydrogen, or alkyl of 1-6 carbon atoms;  
 R 2  and R 3  are each, independently, hydrogen or alkyl of 1-6 carbon atoms;  
 R 4  and R 5  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, -CN, amino or fluorinated alkyl of 1 to 6 carbon atoms;  
 R 6  and R 7  are each independently hydrogen or C 1 -C 6  alkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       9 . The method of  claim 7  wherein the compound administered is at least one compound selected from 
 a) 1,2,3,4,9,10-hexahydro-8H-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    b) 1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    c) 3-acetyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    d) 6-methyl-1,2,3,4,9,10-hexahydro-8H-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    e) 9-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    f) 9,9-dimethyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[1 ,4]diazepino[6,7,1-hi]indole;    or a pharmaceutically acceptable salt thereof.    
   
   
       10 . The method of  claim 7  wherein the compound administered is at least one compound selected from: 
 a) (7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1-hi]indole;    b) (2S)-(rel-7bR,10aR)-2-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    c) (2S)-(rel-7bS,10aS)-2-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    d) (2R)-(rel-7bR,10aR)-2-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    e) (2R)-(rel-7bS,10aS)-2-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    f) (2R,7bS,10aS)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indol-2-ylmethanol;    g) rel-(4S,7bS,10aS)-4-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino [6,7,1-hi]indole;    h) rel-(4R,7bS,10aS)-4-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    i) (7bR,9R,10aR)-9-methyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    j) (7b,10aR)-9,9-dimethyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    k) (7bS,10aS)-9,9-dimethyl-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole;    or a pharmaceutically acceptable salt thereof.    
   
   
       11 .- 17 . (canceled)