Bicyclic Compounds and Methods of Making and Using Same

Abstract

Disclosed herein are compounds that may be modulators of 5-HT receptors, and methods of making and using same.

1 - 32 . (canceled) 
     
     
         33 . A method of treating or ameliorating Alzheimer's disease, or treating a memory disorder in a subject in need thereof, comprising administering a pharmaceutically effective amount of a compound of formula II: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts or N-oxides thereof, wherein
 R 1  is, independently for each occurrence, selected from halogen, hydroxyl, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 3 -C 6  cycloalkyl, C 1 -C 6  alkoxy, nitro, cyano, amino, sulfonyl, C 1 -C 6  alkylsulfonyl, sulfamoyl, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl; 
 B is selected from formulae IIA and IIB: 
 
       
         
           
           
               
               
           
         
         R 2  is selected from C 1 -C 6  alkyl and C 3 -C 6  cycloalkyl, wherein R 2  may be optionally substituted with one, two, or three substituents selected, independently for each occurrence, from halogen, alkoxy, nitro, cyano, amino, and carboxyl; 
         R 3  and R 4  are each independently selected from hydrogen, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, aryl, C 3 -C 6  cycloalkyl halogen, heteroaryl, heterocyclyl, and hydroxyl, wherein R 3  or R 4 , if not hydrogen, may be optionally substituted by one, two, or three substituents represented by R 10 , or R 3  and R 4  are taken together with the carbon atom to which they are attached to form a four, five, or six membered heterocyclyl or C 3 -C 6  cycloalkyl optionally substituted by one, two, or three substituents each represented by R 10 ; 
         R 7  is selected from C 1 -C 6  alkoxy, C 1 -C 6  alkyl, cyano, halogen, hydrogen, and hydroxyl; 
         R 8  is selected from hydrogen and alkyl optionally substituted by one, two, or three substituents each selected from halogen, hydroxyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkoxy, N—C 1 -C 6  alkylamino, N,N-diC 1 -C 6  alkylamino, cyano, carboxyl, sulfonamido, and C 1 -C 6 alkylsulfonamido; 
         R 9  is, independently for each occurrence, selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, sulfonyl, C 1 -C 6 alkylsulfonyl, sulfamoyl, sulfonamido, C 1 -C 6  alkylsulfonamido, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl, C 1 -C 6  alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylthio, and C 1 -C 6 alkoxy, wherein the alkyl, cycloalkyl or alkoxy is optionally substituted by one, two, or three substituents independently selected from halogen, hydroxyl, carboxy, cyano, amido, nitro, and amino; 
         R 10  is, independently for each occurrence, selected from halogen, hydroxyl, nitro, cyano, amino, sulfonyl, C 1 -C 6  alkylsulfonyl, sulfamoyl, sulfonamido, C 1 -C 6  alkylsulfonamido, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl, C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, C 1 -C 6  alkylthio, and C 1 -C 6  alkoxy, wherein the alkyl, cycloalkyl or alkoxy is optionally substituted by one, two, or three substituents independently selected from halogen, hydroxyl, carboxy, cyano, amido, nitro, and amino; and 
         m is 0, 1, 2, 3, or 4. 
       
     
     
         34 . (canceled) 
     
     
         35 . A method of treating or ameliorating Alzheimer's disease, or treating a memory disorder in a subject in need thereof, comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula II: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts or N-oxides thereof, wherein
 R 1  is, independently for each occurrence, selected from halogen, hydroxyl, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 3 -C 6  cycloalkyl, C 1 -C 6  alkoxy, nitro, cyano, amino, sulfonyl, C 1 -C 6  alkylsulfonyl, sulfamoyl, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl; 
 B is selected from formulae IIA and IIB: 
 
       
         
           
           
               
               
           
         
         R 2  is selected from C 1 -C 6  alkyl and C 3 -C 6  cycloalkyl, wherein R 2  may be optionally substituted with one, two, or three substituents selected, independently for each occurrence, from halogen, alkoxy, nitro, cyano, amino, and carboxyl; 
         R 3  and R 4  are each independently selected from hydrogen, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, aryl, C 3 -C 6  cycloalkyl, halogen, heteroaryl, heterocyclyl, and hydroxyl, wherein R 3  or R 4 , if not hydrogen, may be optionally substituted by one, two, or three substituents represented by R 10 , or R 3  and R 4  are taken together with the carbon atom to which they are attached to form a four, five, or six membered heterocyclyl or C 3 -C 6  cycloalkyl optionally substituted by one, two, or three substituents each represented by R 10 ; 
         R 7  is selected from C 1 -C 6  alkoxy, C 1 -C 6  alkyl, cyano, halogen, hydrogen, and hydroxyl; 
         R 8  is selected from hydrogen and alkyl optionally substituted by one, two, or three substituents each selected from halogen, hydroxyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkoxy, N—C 1 -C 6  alkylamino, N,N-diC 1 -C 6  alkylamino, cyano, carboxyl, sulfonamido, and C 1 -C 6 alkylsulfonamido; 
         R 9  is, independently for each occurrence, selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, sulfonyl, C 1 -C 6 alkylsulfonyl, sulfamoyl, sulfonamido, C 1 -C 6  alkylsulfonamido, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl, C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, C 1 -C 6  alkylthio, and C 1 -C 6  alkoxy, wherein the alkyl, cycloalkyl or alkoxy is optionally substituted by one, two, or three substituents independently selected from halogen, hydroxyl, carboxy, cyano, amido, nitro, and amino; 
         R 10  is, independently for each occurrence, selected from halogen, hydroxyl, nitro, cyano, amino, sulfonyl, C 1 -C 6  alkylsulfonyl, sulfamoyl, sulfonamido, C 1 -C 6  alkylsulfonamido, carbamoyl, carboxyl, N—C 1 -C 6  alkylsulfamoyl, and N—C 1 -C 6  alkylcarbamoyl, C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, C 1 -C 6  alkylthio, and C 1 -C 6  alkoxy, wherein the alkyl, cycloalkyl or alkoxy is optionally substituted by one, two, or three substituents independently selected from halogen, hydroxyl, carboxy, cyano, amido, nitro, and amino; and 
         m is 0, 1, 2, 3, or 4. 
       
     
     
         36 . (canceled)