Substituted N-arylsulfonylheterocyclic amines as gamma-secretase inhibitors

A compound of the formula I:

• or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
• L is —O—, —N(R6)—, —S—, —S(O)—, or —S(O2)—;
• R1 is selected from the group consisting of unsubstituted aryl, aryl substituted with one or more substituents R7 which can be the same or different, unsubstituted heteroaryl, and heteroaryl substituted with one or more substituents R7 which can be the same or different;
• R2 is selected from the group consisting of alkyl, alkyl substituted with one or more substituents R7 which can be the same or different, —C(O)—Y, —X—C(O)—Y, -alkylene-X—C(O)—Y, -alkylene-C(O)—Y, -alkylene-cycloalkylene-X—C(O)—Y, -alkylene-cycloalkylene-C(O)—Y, -cycloalkylene-alkylene-X—C(O)—Y, -cycloalkylene-alkylene-C(O)—Y, -cycloalkylene-alkylene-C(O)—Y substituted on the alkylene moiety with one or more hydroxy groups, -cycloalkylene-X—C(O)—Y, -cycloalkylene-C(O)—Y, -alkylene-cycloalkylene-alkylene-X—C(O)—Y, -alkylene-cycloalkylene-alkylene-C(O)—Y, unsubstituted aryl, aryl substituted with one or more substituents R7 which can be the same or different, unsubstituted heteroaryl, and heteroaryl substituted with one or more substituents R7 which can be the same or different;
• R3 is selected from the group consisting of unsubstituted aryl, aryl substituted with one or more substituents R7 which can be the same or different, unsubstituted heteroaryl, heteroaryl substituted with one or more substituents R7 which can be the same or different, unsubstituted alkyl, alkyl substituted with one or more substituents R7 which can be the same or different, unsubstituted cycloalkyl, cycloalkyl substituted with one or more substituents R7 which can be the same or different, alkylene-cycloalkyl, alkylene-cycloalkyl independently substituted on the cycloalkyl moiety with one or more substituents R7, unsubstituted arylalkyl, arylalkyl optionally independently substituted on the aryl moiety with one or more substituents R7 which can be the same or different, unsubstituted arylcycloalkyl, arylcycloalkyl independently substituted on the aryl moiety with one or more substituents R7 which can be the same or different, unsubstituted heteroarylalkyl, heteroarylalkyl independently substituted on the heteroaryl moiety with one or more substituents R7 which can be the same or different, unsubstituted heteroarylcycloalkyl, heteroarylcycloalkyl independently substituted on the heteroaryl moiety with one or more substituents R7 which can be the same or different, unsubstituted arylheterocycloalkyl, arylheterocycloalkyl independently substituted on the aryl moiety with one or more substituents R7 which can be the same or different, and unsubstituted alkoxyalkyl;
• each R4 and R5 is independently selected from the group consisting of H, alkyl, and alkyl independently substituted with one or more substituents R7 which can be the same or different;
• or
• R3 and R4 together with the carbon atoms to which they are shown attached can be linked to form a 4- to 8-membered cycloalkyl or heterocycloalkyl ring;
• R6 is selected from the group consisting of H, alkyl, alkyl independently substituted with one or more substituents R7 which can be the same or different, unsubstituted aryl, and aryl independently substituted with one or more substituents R7 which can be the same or different;
• R7 is selected from the group consisting of halo, —CF3, —OH, alkyl, alkyl substituted with 1 to 4 hydroxy groups, —O-alkyl, —OCF3, —CN, —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, —N(aryl)(alkyl), —C(O)O-alkyl, -alkylene-NH(alkyl), -alkylene-N(alkyl)2, -alkylene-NH(aryl), -alkylene-N(aryl)2, -alkylene-N(aryl)(alkyl), —NHC(O)-alkyl, —N(alkyl)C(O)-alkyl, —N(aryl)C(O)-alkyl, —NHC(O)-aryl, —N(alkyl)C(O)-aryl, —N(aryl)C(O)-aryl, —NHC(O)-heteroaryl, —N(alkyl)C(O)-heteroaryl, —N(aryl)C(O)-heteroaryl, —NHC(O)—NH2, —NHC(O)—NH(alkyl), —NHC(O)—N(alkyl)2, —NHC(O)—NH(aryl), —NHC(O)—N(aryl)2, —NHC(O)—N(alkyl)(aryl), —N(alkyl)C(O)—NH2, —N(alkyl)C(O)—NH(alkyl), —N(alkyl)C(O)—N(alkyl)2, —N(alkyl)C(O)—NH(aryl), —N(alkyl)C(O)—N(aryl)2, —N(alkyl)C(O)—N(alkyl)(aryl), —N(aryl)C(O)—NH2, —N(aryl)C(O)—NH(alkyl), —N(aryl)C(O)—N(alkyl)2, —N(aryl)C(O)—NH(aryl), —N(aryl)C(O)—N(aryl)2, and —N(aryl)C(O)—N(alkyl)(aryl);
• R8 and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, arylalkyl, heteroarylalkyl,
• each R10 is independently selected from the group consisting of H, —OH, alkyl, alkyl substituted with 1 to 4 hydroxy groups, —O-alkyl, —O-alkyl substituted with 1 to 4 hydroxy groups, cycloalkyl, cycloalkyl substituted with 1 to 4 hydroxy groups, —C(O)O-alkyl, -alkylene-C(O)—OH, unsubstituted heterocycloalkyl, heterocycloalkyl substituted with one or more groups R7, -alkylene-C(O)—NH2, -alkylene-C(O)—NH(alkyl), -alkylene-C(O)—N(alkyl)2, -alkylene-C(O)—NH(aryl), -alkylene-C(O)—N(aryl)2, -alkylene-C(O)—N(alkyl)(aryl), —C(O)—NH2, —C(O)—NH(alkyl), —C(O)—N(alkyl)2, —C(O)—NH(aryl), —C(O)—N(aryl)2, —C(O)—N(alkyl)(aryl), —O-cycloalkyl, and —O-cycloalkyl substituted with 1 to 4 hydroxy groups;
• or
• two R10 groups together with the ring carbon atoms to which they are shown attached form a 4- to 7-membered cycloalkyl or heterocycloalkyl ring;
• or
• two R10 groups together with the ring carbon atom to which they are attached form a carbonyl group;
• R11 is H, alkyl, alkyl substituted with 1 to 4 hydroxy groups, cycloalkyl, cycloalkyl substituted with 1 to 4 hydroxy groups, arylalkyl, heteroarylalkyl, —C(O)O-alkyl, —C(O)-alkyl, —C(O)-alkyl wherein said alkyl moiety is substituted with one or more hydroxyl groups, —C(O)-cycloalkyl, —C(O)—NH2, —C(O)—NH(alkyl), —C(O)—N(alkyl)2, —C(O)—NH(aryl), —C(O)—N(aryl)2, —C(O)—N(alkyl)(aryl), —C(O)-alkylene-NH2, —C(O)-alkylene-NH(alkyl), —C(O)-alkylene-N(alkyl)2, —C(O)-alkylene-NH(aryl), —C(O)-alkylene-N(aryl)2, —C(O)-alkylene-N(alkyl)(aryl), —S(O2)-alkyl, -alkylene-C(O)—OH, alkylene-O-alkylene-OH, unsubstituted aryl, aryl independently substituted with one or more substituents R7, unsubstituted heteroaryl, heteroaryl independently substituted with one or more substituents R7, and -alkylene-C(O)O-alkyl;
• X is selected from the group consisting of —O—, —N(R6)—, —O-alkylene- and -alkylene-O—;
• Y is selected from the group consisting of —NR8R9, —N(R6)—(CH2)b—NR8R9 wherein b is an integer of from 2 to 6, unsubstituted aryl, aryl independently substituted with one or more substituents R7 which may be the same or different, unsubstituted heteroaryl, heteroaryl independently substituted with one or more substituents R7 which may be the same or different, alkyl, cycloalkyl, unsubstituted arylalkyl, arylalkyl independently substituted on the aryl moiety with one or more substituents R7 which may be the same or different, unsubstituted arylcycloalkyl, arylcycloalkyl independently substituted on the aryl moiety with one or more substituents R7 which may be the same or different, unsubstituted heteroarylalkyl, heteroarylalkyl independently substituted on the heteroaryl moiety with one or more substituents R7 which may be the same or different, unsubstituted heteroarylcycloalkyl, heteroarylcycloalkyl independently substituted on the heteroaryl moiety with one or more substituents R7 which may be the same or different, unsubstituted heterocycloalkyl, heterocycloalkyl independently substituted with one or more substituents R7 which may be the same or different, unsubstituted arylheterocycloalkyl, and arylheterocycloalkyl independently substituted on the aryl moiety with one or more substituents R7 which may be the same or different;
• or
• Y is selected from the group consisting of:
• Z is selected from the group consisting of H, —OH, —O-alkyl, unsubstituted heterocycloalkyl, heterocycloalkyl optionally independently substituted with one or more substituents R14 which may be the same or different, —NR8R9, —NR8R13, unsubstituted benzo-fused heterocycloalkyl, and benzo-fused heterocycloalkyl optionally independently substituted on the benzo- or heterocycloalkyl moiety with one or more substituents R14 which may be the same or different;
• each R12 is independently H or alkyl;
• R13 is selected from the group consisting of H, unsubstituted heterocycloalkyl, heterocycloalkyl independently substituted with one or more substituents R14 which may be the same or different, unsubstituted arylalkyl, arylalkyl independently substituted on the aryl moiety with one or more substituents R14 which may be the same or different, unsubstituted heteroarylalkyl, heteroarylalkyl optionally independently substituted on the heteroaryl moiety with one or more substituents R14 which may be the same or different, unsubstituted cycloalkyl, cycloalkyl optionally independently substituted with one or more substituents R14 which may be the same or different, unsubstituted -alkylene-cycloalkyl, -alkylene-cycloalkyl independently substituted on the cycloalkyl moiety with one or more substituents R14 which may be the same or different, unsubstituted -alkylene-heterocycloalkyl, and -alkylene-heterocycloalkyl independently substituted on the heterocycloalkyl moiety with one or more substituents R14 which may be the same or different;
• R14 is selected from the group consisting of halo, —CF3, —OH, —O-alkyl, —OCF3, —CN, —NR8R9, —C(O)-alkyl, —C(O)-aryl, —C(O)—NR8R9, —C(O)O-alkyl, -alkylene-NR8R9, -alkylene-C(O)O-alkyl, —N(R8)C(O)-alkyl, —N(R8)C(O)-aryl, —N(R8)C(O)-heteroaryl, —N(R8)C(O)—NR8R9, piperidinyl, pyrrolidinyl, aryl, heteroaryl, and —O—CH2—CH2—O—, wherein both oxygen atoms of said —O—CH2—CH2—O— are bound to the same carbon atom and with the proviso that aryl and heteroaryl moieties are not substituted with said —O—CH2—CH2—O— group;
• m and n can be the same or different and are integers of from 0 to 3;
• p is an integer of from 1 to 4;
• r is an integer of from 1 to 3;
• and
• t is an integer of from 0 to 2.