Hormone receptor modulators for treating metabolic conditions and disorders

Abstract

wherein L1, A, X1, X2, R1, R2, and R3 are described herein.

What is claimed is: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a salt thereof, 
         wherein: 
         one of X 1  or X 2  is NR x  or N + (O − )R x  and the other is CHR y  or C(O); 
         R x  is 
       
       
         
           
           
               
               
           
         
         R y  is H, alkyl, cycloalkyl or cycloalkylalkyl wherein said alkyl, cycloalkyl and cycloalkylalkyl are optionally substituted with halogen or alkoxy; 
         L 1  is —(CH 2 ) m (C═O)— or —(CH 2 ) p —; 
         L 2  is a bond or —S(O) 2 —; 
         A is cycloalkyl, aryl, heterocycloalkyl or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more R 7 ; 
         B is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more R 5 ; 
         R 1  and R 2  are each independently H, alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, cycloalkyl, or CN, wherein the cycloalkyl is optionally substituted with one or more R 9 ; 
         or when A is cycloalkyl or heterocycloalkyl, R 1  and R 2  together when attached to the same carbon atom form a spirocycloalkyl ring optionally substituted with one or more R 8 ; or when A is cycloalkyl or heterocycloalkyl, R 1  and R 2  together when attached to the same atom form a spiroheterocycloalkyl ring optionally substituted with one or more R 8 ; or R 1  and R 2  when on adjacent atoms together with the atoms to which they are attached form a cycloalkyl ring optionally substituted with one or more R 8 ; or R 1  and R 2  when on adjacent atoms together with the atoms to which they are attached form a heterocycloalkyl ring optionally substituted with one or more R 8 ; or R 1  and R 2  when on adjacent atoms together with the atoms to which they are attached form an aryl ring optionally substituted with one or more R 8 ; or R 1  and R 2  when on adjacent atoms together with the atoms to which they are attached form a heteroaryl ring optionally substituted with one or more R 8 ; or when A is cycloalkyl or heterocycloalkyl, R 1  and R 2  when on non-adjacent atoms, together with the atoms to which they are attached form a cycloalkyl ring optionally substituted with one or more R 8 ; or when cycloalkyl or heterocycloalkyl, R 1  and R 2  when on non-adjacent atoms, together with the atoms to which they are attached form a heterocycloalkyl ring optionally substituted with one or more R 8 ; cycloalkyl ring optionally substituted with one or more R 8 ; or when cycloalkyl or heterocycloalkyl, R 1  and R 2  together with the atoms to which they are attached form a heterocycloalkyl ring optionally substituted with one or more R 8 ; 
         R 3  is alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, or cycloalkyl optionally substituted with one or more substituents each independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, and —OH; 
         R 4  is COOR 6a , —(CH 2 ) n —COOR 6a , CONR 6b OH, CONR 6b R 6c , CONH(CH 2 ) n COOR 6a , CONH(CH 2 ) n R 6a , —(CH 2 ) n CONH(CH 2 ) n R 6a , CONR 6b SO 2 R 6d , CONR 6b SO 2 (CH 2 ) n R 6d , —(CH 2 ) n —CONR 6b SO 2 R 6d , CONR 6b SO 2 (CH 2 ) n N(CO)R 6d  CONH(CH 2 ) n SO 2 R 6e , COR 6f , (CH 2 ) n PO(OR 6g ) 2 , CONR 6b (CH 2 ) n PO(OR 6g ) 2 , CONR 6b SO 2 (CH 2 ) n N + (R 6f ) 3 , COO(CH 2 ) n PO(OR 6g ) 2 , SO 2 NR 6b (CH 2 ) n COOR 6a , SO 2 R 6e , CN, —(CH 2 ) n —NR 6b C(O)R 6c , —(CH 2 ) n —N(OH)—C(O)R 6c , oxo, alkyl, cycloalkyl, —(CH 2 ) n -cycloalkyl, heterocycloalkyl, —(CH 2 ) n -heterocycloalkyl, heteroaryl or —(CH 2 ) n -heteroaryl; wherein said alkyl, cycloalkyl, —(CH 2 ) n -cycloalkyl, heterocycloalkyl, —(CH 2 ) n -heterocycloalkyl, heteroaryl and —(CH 2 ) n -heteroaryl are optionally substituted with COOR 6a , —(CH 2 ) n —COOR 6a , CONR 6b OH, CONR 6b R 6c , CONH(CH 2 ) n COOR 6a , CONH(CH 2 ) n R 6a , —(CH 2 ) n CONH(CH 2 ) n R 6a , CONR 6b SO 2 R 6d , CONR 6b SO 2 (CH 2 ) n R 6d , —(CH 2 ) n —CONR 6b SO 2 R 6d , CONR 6b SO 2 (CH 2 ) n N(CO)R 6d  CONH(CH 2 ) n SO 2 R 6e , COR 6f , (CH 2 ) n PO(OR 6g ) 2 , COO(CH 2 ) n PO(OR 6g ) 2 , SO 2 NR 6b (CH 2 ) n COOR 6a , SO 2 R 6e , CN, —(CH 2 ) n —NR 6b C(O)R 6c , or —(CH 2 ) n —N(OH)—C(O)R 6c ; 
         each R 5  is independently at each occurrence halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, CN, cycloalkyl, spiroheterocycloalkyl, —O-cycloalkyl, —O-heterocycloalkyl, aryl, heterocycloalkyl, or heteroaryl wherein the cycloalkyl, aryl, heterocycloalkyl or heteroaryl are optionally substituted with one or more substituents each independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy; 
         R 6a  is H, alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, NR 6b R 6c , SO 2 NR 6b R 6c , and —OH; 
         R 6b  and R 6c  are each independently H, alkyl, haloalkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, and —OH; 
         R 6d  is alkyl, haloalkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl; wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, COOH, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, —O—CO-alkyl, —O—COcycloalkyl, —O—CO-alkyl-COOH, NR 6b R 6c , NR 6f CO-alkyl, NR 6f CO-alkoxy, cycloalkyl, heterocycloalkyl and —OH; 
         R 6e  is —OH, alkyl, haloalkyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl; wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, and —OH; 
         R 6f  is alkyl or haloalkyl; 
         R 6g  is H or alkyl optionally substituted with —O—CO-alkyl; 
         each R 7  is independently at each occurrence OH, alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, or CN; 
         each R 8  is independently at each occurrence alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, or —OH; 
         each R 9  is independently at each occurrence alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, or —OH; 
         m is 0, 1, or 2; 
         n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; and 
         p is 1 or 2.