Gamma secretase modulators

1. A compound of the formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is a phenyl ring optionally substituted by a halogen, alkoxy or haloalkyl group;

L is selected from the group consisting of: L is a direct bond, —O—, —N(R 5 )—, —C(R 6 )(R 7 )—, —(C═O)—, —(C═NR 21A )—, —S—, —S(O)—, and —S(O) 2 —;

R 2 is the fused bicyclic ring:

wherein:

(1) Ring (A) is a five membered heteroaryl ring comprising atoms A 1 to A 5 , wherein the dashed circle in Ring A represent a sufficient number of bonds for Ring (A) to be a heteroaryl ring:

(a) A 1 , A 4 , and A 5 are each C,

(b) A 2 and A 3 are each N wherein each substitutable N is optionally substituted with one R 21A group and each R 21A for each N is independently selected,

(2) Ring (B) (which comprises atoms A 4 , A 5 , and B 1 to B 4 ) is a heterocycloalkenyl ring, wherein

A 4 and A 5 are as defined for Ring (A) above,

B 1 is N;

B 2 to B 4 is C;

wherein each substitutable A 4 , A 5 , and

B 2 to B 4 is optionally substituted with 1 or 2 independently selected R 21B groups,

and wherein said heterocycloalkenyl Ring (B) comprises two double bonds;

R 3 is an alkoxy substituted phenyl ring;

R 4 is an imidazol-1-yl ring optionally substituted with an alkyl group or an alkyl and halo group;

R 5 is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN, —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —S(O)N(R 15 )(R 16 ), —S(O) 2 N(R 15 )(R 16 ), —C(═NOR 15 )R 16 , and —P(O)(OR 15 )(OR 16 ); or

R 5 taken together with R 1 and the nitrogen to which they are bound form a heterocycloalkyl or heterocycloalkenyl ring fused to said R 1 ring said fused ring is optionally substituted with 1 to 5 independently selected R 21 groups;

R 6 and R 7 are each independently selected from the group consisting of: H, alkyl, alkenyl, alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclylalkyl-, wherein independently each of said alkyl, alkenyl and alkynyl, aryl, arylalkyl-, alkylaryl-, cycloalkyl, cycloalkylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl and heterocyclylalkyl- is optionally substituted with 1 to 5 independently selected R 21 groups; or

R 6 taken together with R 1 and the carbon to which they are bound form a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl ring fused to said R 1 ring, said fused ring is optionally substituted with 1 to 5 independently selected R 21 groups; or

R 6 and R 7 taken together with the carbon to which they are bound form a spirocycloalkyl ring, a spirocycloalkenyl ring, a spiroheterocycloalkyl ring, or a spiroheterocycloalkenyl ring, and wherein the spiro ring is optionally substituted with 1-5 independently selected R 21 groups;

R 15A and R 16A are independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, arylheterocyclyl, (R 18 ) q -alkyl,

(R 18 ) q -cycloalkyl, (R 18 ) q -cycloalkylalkyl, (R 18 ) q -heterocyclyl, (R 18 ) q -heterocyclylalkyl, (R 18 ) q -aryl, (R 18 ) q -arylalkyl, (R 18 ) q -heteroaryl and (R 18 ) q heteroarylalkyl, wherein q is 1 to 5;

R 15 , R 16 and R 17 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, arylheterocyclyl, (R 18 ) q -alkyl,

(R 18 ) q -cycloalkyl, (R 18 ) q -cycloalkylalkyl, (R 18 ) q -heterocyclyl, (R 18 ) q -heterocyclylalkyl, (R 18 ) q -aryl, (R 18 ) q -arylalkyl, (R 18 ) q -heteroaryl and (R 18 ) q heteroarylalkyl, wherein q is 1 to 5 and each R 18 is independently selected (and those skilled in the art will appreciate that the R 18 moieties can be bound to any available substitutable atom);

each R 18 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO 2 , halo, heteroaryl, HO-alkyoxyalkyl, —CF 3 , —CN, alkyl-CN, —C(O)R 19 , —C(O)OH, —C(O)OR 19 , —C(O)NHR 20 , —C(O)NH 2 , —C(O)NH 2 —C(O)N(alkyl) 2 , —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR 19 , —S(O) 2 R 20 , —S(O)NH 2 , —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O) 2 NH 2 , —S(O) 2 NHR 19 , —S(O) 2 NH(heterocyclyl), —S(O) 2 N(alkyl) 2 , —S(O) 2 N(alkyl)(aryl), —OCF 3 , —OH, —OR 20 , —O-heterocyclyl, —O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH 2 , —NHR 20 , —N(alkyl) 2 , —N(arylalkyl) 2 , —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R 20 , —NHC(O)NH 2 , —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O) 2 R 20 , —NHS(O) 2 NH(alkyl), —NHS(O) 2 N(alkyl)(alkyl), —N(alkyl)S(O) 2 NH(alkyl) and —N(alkyl)S(O) 2 N(alkyl)(alkyl); or alternately, two R 18 moieties on adjacent carbons can be linked together to form:

R 19 is alkyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;

R 20 is alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;

each R 21 group is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR 15 , —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —P(O)(CH 3 ) 2 , —SO(═NR 15 )R 16 —, —SF 5 , —OSF 5 , —Si(R 15A ) 3 wherein each R 15A is independently selected, —SR 15 , —S(O)N(R 15 )(R 16 ), —CH(R 15 )(R 16 ), —S(O) 2 N(R 15 )(R 16 ), —C(═NOR 15 )R 16 , —P(O)(OR 15 )(OR 16 ), —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —R 15 , —CH 2 N(R 15 )(R 16 ), —N(R 15 )S(O)R 16A , —N(R 15 )S(O) 2 R 16A , —CH 2 —N(R 15 )S(O) 2 R 16A , —N(R 15 )S(O) 2 N(R 16 )(R 17 ), —N(R 15 )S(O)N(R 16 )(R 17 ), —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , —S(O)R 15A , ═NOR 15 , —N 3 , —NO 2 , —S(O) 2 R 15A , —O—N═C(R 15 ) 2 (wherein each R 15 is independently selected), and —O—N═C(R 15 ) 2 wherein said R 15 groups are taken together with the carbon atom to which they are bound to form a 5 to 10 membered ring and wherein said ring optionally contains 1 to 3 heteroatoms independently selected from the group consisting of —O—, —O—, —S(O)—, —S(O) 2 —, and —NR 21A ;

each R 21A is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —OR 15 , —CN, -alkyl-(R 15 )(R 16 ), —CH(R 15 )(R 16 ), —CH 2 —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —R 15 ; —CH 2 N(R 15 )(R 16 ), —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —C(═NOR 15 )R 16 , —CH 2 —N(R 15 )S(O) 2 R 16A , —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —N(R 15 )C(O)OR 16 , —C(R 15 )═NOR 16 , —S(O)R 15A ; —S(O)(OR 15 ), —S(O) 2 (O R 15 ), —S(O) 2 R 15A , —S(O)N(R 15 )(R 16 ), —S(O) 2 N(R 15 )(R 16 ), —P(O)(OR 15 )(OR 16 ), —N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16A , —N(R 15 )S(O) 2 R 16A , —N(R 15 )S(O) 2 N(R 16 )(R 17 ), —N(R 15 )S(O)N(R 16 )(R 17 ), —N(R 15 )C(O)N(R 16 )(R 17 ), —N(R 15 )C(O)OR 16 ,—N 3 , —NO 2 , —P(O)(CH 3 ) 2 , —SO(═NR 15 )R 16 —, —SF 5 , and —OSF 5 ;

each R 21B group is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —OR 15 , —CN, -alkyl-(R 15 )(R 16 ), —CH(R 15 )(R 16 ), —CH 2 —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —R 15 , —CH 2 N(R 15 )(R 16 ), —C(O)R 15 , —C(O)OR 15 , —C(O)N(R 15 )(R 16 ), —C(═NOR 15 )R 16 , —CH 2 —N(R 15 )S(O) 2 R 16A , —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —N(R 15 )C(O)OR 16 , —C(R 15 )═NOR 16 , —SR 15 ; —S(O)R 15A ; —S(O)(OR 15 ), —S(O) 2 (OR 15 ), —S(O) 2 R 15A , —S(O)N(R 15 )(R 16 ), —S(O) 2 N(R 15 )(R 16 ), —P(O)(OR 15 )(OR 16 ), —N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16A , —N(R 15 )S(O) 2 R 16A , —N(R 15 )S(O) 2 N(R 16 )(R 17 ), —N(R 15 )S(O)N(R 16 )(R 17 ), —N(R 15 )C(O)N(R 16 )(R 17 ), —N(R 15 )C(O)OR 16 ,—N 3 , —NO 2 , —P(O)(CH 3 ) 2 , —SO(═NR 15 )R 16 —, —SF 5 , —OSF 5 , and —Si(R 15A ) 3 wherein each R 15A is independently selected; and wherein each alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl R 21 , R 21A , and R 21B group is optionally substituted by 1 to 5 independently selected R 22 groups wherein each R 22 group is independently selected from the group consisting of alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, halo, —CF 3 , —CN, —OR 15 , —C(O)R 15 , —C(O)OR 15 , -alkyl-C(O)OR 15 , C(O)N(R 15 )(R 16 ), ——SR 15 , —S(O)N(R 15 )(R 16 ),

—S(O) 2 N(R 15 )(R 16 ), —C(═NOR 15 )R 16 , —P(O)(OR 15 )(OR 16 ), —N(R 15 )(R 16 ), -alkyl-N(R 15 )(R 16 ), —N(R 15 )C(O)R 16 , —CH 2 —N(R 15 )C(O)R 16 , —N(R 15 )S(O)R 16 , —N(R 15 )S(O) 2 R 16 , —CH 2 —N(R 15 )S(O) 2 R 16 , —N(R 15 )S(O) 2 N(R 16 )(R 17 ), —N(R 15 )S(O)N(R 16 )(R 17 ), —N(R 15 )C(O)N(R 16 )(R 17 ), —CH 2 —N(R 15 )C(O)N(R 16 )(R 17 ), —N(R 15 )C(O)OR 16 , —CH 2 —N(R 15 )C(O)OR 16 , —N 3 , ═NOR 15 , —NO 2 , —S(O)R 15A and —S(O) 2 R 15 A.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of:

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L is selected from the group consisting of:

and

R 1 selected from the group consisting of:

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the R 4 —R 3 — moiety is:

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein:

(a) the R 4 —R 3 — moiety is selected from the group consisting of:

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein:

(a) L is —C(R 6 )(R 7 )— wherein R 6 and R 7 are independently selected from the group consisting of:

H and alkyl; or

(b) L is —C(R 6 )(R 7 )— wherein R 6 is taken together with R 1 and the carbon to which they are bound to form a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl ring fused to said R 1 ring, said fused ring is optionally substituted with 1 to 5 independently selected R 21 groups; or

(c) L is is —N(R 5 )—, and R 5 taken together with R 1 and the nitrogen to which they are bound form a heterocycloalkyl or heterocycloalkenyl ring fused to said R 1 ring.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

8. A pharmaceutical composition comprising: a therapeutically effective amount of at least one compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.