Substituted lactams as inhibitors of Aβ protein production

1. A compound of Formula (I):

or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

Q is —(CR 7 R 7a ) m —R 4 ,

—(CR 7 R 7a ) n —S—R 4 ,

—(CR 7 R 7a ) n —O—R 4 ,

—(CR 7 R 7a ) m —N(R 7b )—R 4 ,

—(CR 7 R 7a ) n —S(═O)—R 4 ,

—(CR 7 R 7a ) n —S(═O) 2 —R 4 , or

—(CR 7 R 7a ) n —C(═O)—R 4 ;

provided when n is 0, then R 4 is not H;

m is 1;

n is 0, 1, or 2;

R 4 is H,

C 1 -C 8 alkyl substituted with 0-3 R 4a ,

C 2 -C 8 alkenyl substituted with 0-3 R 4a ,

C 2 -C 8 alkynyl substituted with 0-3 R 4a ,

C 3 -C 10 carbocycle substituted with 0-3 R 4b ,

aryl substituted with 0-3 R 4b , or

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;

R 4a , at each occurrence, is independently selected from is H, Cl, F, Br, I, CN, NO 2 ,NR 15 R 16 ,

CF 3 , OR 14a , OR 22 , SR 22 , C(═O)OR 22 , NR 21 R 22 , S(═O)R 22 , S(═O) 2 R 22 ,

C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl,

C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkyl-S—,

C 3 -C 10 carbocycle substituted with 0-3 R 4b ,

aryl substituted with 0-3 R 4b , and

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;

R 4b , at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 ,

NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 ,

C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl,

C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;

R 5 is;

C 1 -C 6 alkyl substituted with 0-3 R 5b ;

C 2 -C 6 alkenyl substituted with 0-3 R 5b ;

C 2 -C 6 alkynyl substituted with 0-3 R 5b ;

C 3 -C 10 carbocycle substituted with 0-3 R 5c ;

aryl substituted with 0-3 R 5c ; and

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 5c ;

R 5b , at each occurrence, is independently selected from:

H, C 1 -C 6 alkyl, CF 3 , Cl, F, Br, I, ═O, CN, NO 2 , NR 15 R 16 ;

C 3 -C 10 carbocycle substituted with 0-3 R 5c ;

aryl substituted with 0-3 R 5c ; or

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 5c ;

R 5c , at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 ,

NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 ,

C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and

C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;

R 6 is H;

C 1 -C 6 alkyl substituted with 0-3 R 6a ;

C 3 -C 10 carbocycle substituted with 0-3 R 6b ; or

aryl substituted with 0-3 R 6b ;

R 6a , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ═O,

CN, NO 2 , NR 15 R 16 , aryl or CF 3 ;

R 6b , at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 ,

NR 15 R 16 , CF 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;

R 7 , at each occurrence, is independently H or C 1 -C 4 alkyl;

R 7a , at each occurrence, is independently H or C 1 -C 4 alkyl;

R 7b is H or C 1 -C 4 alkyl;

Ring B

R 10 is H, C(═O)R 17 , C(═O)OR 17 , C(═O)NR 18 R 19 ,

S(═O) 2 NR 18 R 19 , S(═O) 2 R 17 ;

C 1 -C 6 alkyl optionally substituted with 0-3 R 10a

aryl substituted with 0-4 R 10b ;

C 3 -C 10 carbocycle substituted with 0-3 R 10b ; or

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 10b ;

R 10a , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ═O,

CN, NO 2 , NR 15 R 16 , CF 3 , or aryl substituted with 0-4 R 10b ;

R 10b , at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 ,

NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy,

C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;

W is a bond

X is a bond;

Y is a bond

Z is H;

C 1 -C 8 alkyl substituted with 0-3 R 12a ;

C 2 -C 6 alkenyl substituted with 0-3 R 12a ;

C 2 -C 6 alkynyl substituted with 0-3 R 12a ;

aryl substituted with 0-4 R 12b ;

C 3 -C 10 carbocycle substituted with 0-4 R 12b ; or

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 12b ;

R 12a , at each occurrence, is independently selected from

H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , —C(═O)NR 15 R 16 , CF 3 , acetyl, SCH 3 ,

S(═O)CH 3 , S(═O) 2 CH 3 ,

C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl,

C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkyl-S—,

aryl substituted with 0-4 R 12b ;

C 3 -C 10 carbocycle substituted with 0-4 R 12b ; or

5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 12b ;

R 12b , at each occurrence, is independently selected from

H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 ,

aryl, C 3 -C 6 cycloalkyl,

C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl,

C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;

R 13 , at each occurrence, is independently selected from

H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;

R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;

R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl;

R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl,

(C 1 -C 6 alkyl)-C(═O)—, and (C 1 -C 6 alkyl)-S(═O) 2 —;

R 16 , at each occurrence is independently selected from

H, OH, C 1 -C 6 alkyl, benzyl, phenethyl,

(C 1 -C 6 alkyl)-C(═O)—, and (C 1 -C 6 alkyl)-S(═O) 2 —;

alternatively, R 15 and R 16 , together with the nitrogen to which they are attached, may combine to form a 4-7 membered ring wherein said 4-7 membered ring optionally contains an additional heteroatom selected from O or NH;

R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl,

aryl substituted by 0-4 R 17a , or

—CH 2 -aryl substituted by 0-4 R 17a ;

R 17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF 3 , OCF 3 , SCH 3 , S(O)CH 3 , SO 2 CH 3 , —NH 2 , —N(CH 3 ) 2 , or C 1 -C 4 haloalkyl;

R 18 , at each occurrence, is independently selected from

H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl,

(C 1 -C 6 alkyl)-C(═O)—, and (C 1 -C 6 alkyl)-S(═O) 2 —;

R 19 , at each occurrence, is independently selected from

H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl,

(C 1 -C 6 alkyl)-C(═O)—, and (C 1 -C 6 alkyl)-S(═O) 2 —;

R 19b , at each occurrence, is independently is H or C 1 -C 4 alkyl;

R 21 is H, phenyl, benzyl, or C 1 -C 4 alkyl; and

R 22 is C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or C 3 -C 4 alkynyl.

2. A compound according to claim 1 of Formula (Ig):

or a stereoisomer, or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 of Formula (Ih):

or a stereoisomer, or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising a compound of claim 1 , or a stereoisomer or a pharmaceutically acceptable salt, thereof; and a pharmaceutically acceptable carrier.

5. A method for the treatment of Alzheimer's Disease comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 or a stereoisomer, or a pharmaceutically acceptable salt thereof, comprising a structure according to Formula (I), selected from:

wherein Q and R 5 are described, respectively, in the following moieties:

7. A pharmaceutical composition comprising a compound of claim 6 , or a stereoisomer or a pharmaceutically acceptable salt, thereof, and a pharmaceutically acceptable carrier.

8. A method for the treatment of Alzheimer's Disease comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 6 , or a stereoisomer or pharmaceutically acceptable salt thereof.