IP Library › Granted Patent US 7,390,802

Granted Patent B2

US 7,390,802 · App. 11/655,637 · Granted Jun 24, 2008

Substituted lactams as inhibitors of Aβ protein production

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Quick Facts

Patent No.: US 7,390,802
App. No.: 11/655,637
Granted: Jun 24, 2008
Kind: B2

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Abstract

This invention relates to novel lactams of Formula (I): having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

Claims (891)

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, 2, or 3;

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 H;

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 is

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 ;

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 or —(CR 8 R 8a ) p —;

p is 0, 1, 2, 3, or 4;

R 8 and R 8a , at each occurrence, are independently selected from H, F, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl and C 3 -C 8 cycloalkyl;

X is a bond;

aryl substituted with 0-3 R Xb ;

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

5 to 10 membered heterocycle substituted with 0-2 R Xb ;

R Xb , 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 halothioalkoxy;

Y is a bond or —(CR 9 R 9a ) t —V—(CR 9 R 9a ) u —;

t is 0, 1, or 2;

u is 0, 1, or 2;

R 9 and R 9a , at each occurrence, are independently selected from H, F, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;

V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)—NR 19b —, —NR 19b C(═O)—, —NR 19b S(═O) 2 —, —S(═O) 2 NR 19b —, —NR 19b S(═O)—, —S(═O)NR 19b —, —C(═O)O—, or —OC(═O)—;

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

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 (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 , or

—(CR 7 R 7a ) m —N(R 7b )—R 4 ;

m is 1 or 2;

n is 0 or 1;

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 , C(═O)OR 22 , SR 22 , 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 H;

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, methyl, or ethyl;

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 is

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 ;

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 ;

W is a bond or —(CH 2 ) p —;

p is 1 or 2;

X is a bond;

phenyl substituted with 0-2 R Xb ;

C 3 -C 6 carbocycle substituted with 0-2 R Xb ; or

5 to 6 membered heterocycle substituted with 0-2 R Xb ;

R Xb , 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 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, and C 1 -C 3 halothioalkoxy;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)NR 19b —, —NR 19b C(═O)—, —NR 19b S(O) 2 —, —S(O) 2 NR 19b —, —NR 19b S(O)—, —S(O)NR 19b —, —C(═O)O—, or —OC(═O)—;

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 ,

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

OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , N 1 R 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, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;

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.

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

4. 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 a pharmaceutically acceptable salt thereof.

5. A compound, according to claim 2 , of Formula (Ib):

(Ib)

or a stereoisomer or a pharmaceutically acceptable salt thereof,

wherein:

Q is —(CHR 7 ) m —R 4 ,

—(CHR 7 ) n —s—R 4 ,

—(CHR 7 ) n —O—R 4 , or

—(CHR 7 ) m —N(R 7b )—R 4 ;

m is 1 or 2;

n is 0 or 1;

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 , C(═O)OR 22 , SR 22 , 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 H;

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 , N R 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 7 , at each occurrence, is independently H, methyl, or ethyl;

R 7b is H, methyl, or ethyl;

Ring B is:

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 ;

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 ,

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

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, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;

R 21 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl; and

R 22 is methyl, ethyl, propyl, butyl, propenyl, butenyl, and propargyl.

6. A compound according to claim 5 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof,

wherein:

Q is —(CH 2 ) m —R 4 ,

—(CH 2 ) m —S—R 4 ,

—(CH 2 ) n —O—R 4 , or

—(CH 2 ) m —N(H)-R 4 ;

m is 1 or 2;

n is 0 or 1;

R 4 is 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 , C(═O)OR 22 , SR 22 , OR 22 , OR 14a , 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 H;

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 , N R 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 halo alkoxy;

Ring B is:

wherein

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 ; or

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

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 ; and wherein said 5 to 10 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, isoxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, quinolinyl, and isoquinolinyl;

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 ,

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

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 4 alkyl)-C(═O)—, and (C 1 -C 4 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 4 alkyl)-C(═O)—, and (C 1 -C 4 alkyl)-S(═O) 2 —; and

alternatively, R 15 and R 16 , together with the nitrogen to

which they are attached, may combine to form a 4-6

membered ring wherein said 4-6 membered ring

optionally contains an additional heteroatom selected

from O or NH, wherein said 4-6 membered ring is

selected from imidazolidinyl, oxazolidinyl, thiazolidinyl, piperazinyl, morpholinyl, and thiomorpholinyl;

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, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;

R 21 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl; and

R 22 is methyl, ethyl, propyl, butyl, propenyl, butenyl, and propargyl.

7. A compound according to claim 6 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt wherein:

Q is —CH 2 R 4 , —O—R 4 , or —CH 2 —NH—R 4 ;

R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,

C 2 -C 6 alkenyl substituted with 0-3 R 4a ,

C 2 -C 6 alkynyl substituted with 0-3 R 4a ,

C 3 -C 6 carbocycle substituted with 0-3 R 4b ,

phenyl substituted with 0-3 R 4b , or

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4a ;

R 4a , at each occurrence, is independently selected from H, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , C(═O)OR 22 , SR 22 , OR 14a , 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 halo alkyl,

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 H;

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

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

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

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

H, methyl, ethyl, propyl, butyl, CF 3 , Cl, F, Br, I, ═O;

C 3 -C 6 carbocycle substituted with 0-3 R 5c ;

phenyl substituted with 0-3 R 5c ; and

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 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 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and

C 1 -C 2 haloalkoxy;

Ring B is:

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 ;

W is a bond;

X is a bond;

Y is a bond;

Z is H;

C 1 -C 4 alkyl substituted with 0-3 R 12a ;

C 2 -C 4 alkenyl substituted with 0-3 R 12a ; or

C 2 -C 4 alkynyl substituted with 0-3 R 12a ;

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

H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 1 -C 4 alkyl,

C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 13 , at each occurrence, is independently selected from

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 4 alkyl, or C 2 -C 4 alkoxyalkyl;

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 4 alkyl, and benzyl;

R 16 , at each occurrence, is independently selected from

H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—, ethyl-C(═O)—,

methyl-S(═O) 2 —, and ethyl-S(═O) 2 —;

R 18 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

R 19 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, and butyl;

R 21 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl; and

R 22 is methyl, ethyl, propyl, butyl, propenyl, butenyl, and propargyl.

8. A compound according to claim 7 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof wherein:

Q is —CH 2 R 4 , —O—R 4 , or —CH 2 —NH—R 4 ;

R 4 is C 1 -C 6 alkyl substituted with 0-2 R 4a ,

C 2 -C 6 alkenyl substituted with 0-2 R 4a ,

C 2 -C 6 alkynyl substituted with 0-2 R 4a , or

C 3 -C 6 cycloalkyl substituted with 0-3 R 4b ;

R 4a , at each occurrence, is independently selected from is H, OH, F, Cl, Br, I, CN, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, OCF 3 ;

C 3 -C 6 carbocycle substituted with 0-3 R 4b ,

phenyl substituted with 0-3 R 4b , or

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;

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 H;

C 1 -C 4 alkyl substituted with 0-1 R 5b ;

C 2 -C 4 alkenyl substituted with 0-1 R 5b ; or

C 2 -C 4 alkynyl substituted with 0-1 R 5b ;

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

H, methyl, ethyl, propyl, butyl, CF 3 ;

C 3 -C 6 carbocycle substituted with 0-2 R 5c ;

phenyl substituted with 0-3 R 5c ; and

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 5c ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;

R 5c , at each occurrence, is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

the B ring is:

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 ;

W is a bond;

X is a bond;

Y is a bond;

Z is H;

C 1 -C 4 alkyl substituted with 0-1 R 12a ;

C 2 -C 4 alkenyl substituted with 0-1 R 12a ; or

C 2 -C 4 alkynyl substituted with 0-1 R 12a ;

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

H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , methyl, ethyl,

propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 13 , at each occurrence, is independently selected from

OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR 15 R 16 , and CF 3 ;

R 14 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl; and

R 16 , at each occurrence, is independently selected from

H, OH, methyl, ethyl, propyl, butyl, benzyl, and phenethyl;

R 18 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and

R 19 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, and butyl.

9. A compound according to claim 8 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof wherein:

R 5 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(CH 3 ) 2 , —CH 2 N(CH 2 CH 3 ) 2 , —CH 2 CH 2 NH 2 , —CH 2 CH 2 N(CH 3 ) 2 , —CH 2 CH 2 N(CH 2 CH 3 ) 2 , —CH 2 -cyclopropyl, —CH 2 -cyclobutyl,

—CH 2 -cyclopentyl, —CH 2 -eyclohexyl,

—CH 2 CH 2 -cyclopropyl, —CH 2 CH 2 -cyclobutyl,

—CH 2 CH 2 -cyclopentyl, or —CH 2 CH 2 -cyclohexyl;

Q is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ,

—CH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 -cyclopropyl,

—CH 2 -cyclobutyl, —CH 2 -cyelopentyl, —CH 2 -cyclohexyl,

—CH 2 CH 2 -cyclopropyl, —CH 2 CH 2 -cyclobutyl,

—CH 2 CH 2 -cyclopentyl, —CH 2 CH 2 -cyclohexyl,

—OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH(CH 3 ) 2 ,

—OCH 2 CH 2 CH 2 CH 3 , —OCH 2 CH(CH 3 ) 2 , —OCH 2 CH 2 CH(CH 3 ) 2 ,

—OCH 2 CH 2 CH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ,

—OCH 2 CH 2 CH 2 CH(CH 3 ) 2 , —OCH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 ,

—OCH 2 -cyclopropyl, —OCH 2 -cyclobutyl,

—OCH 2 -cyclopentyl, —OCH 2 -cyclohexyl,

—OCH 2 CH 2 -cyclopropyl, —OCH 2 CH 2 -cyclobutyl,

—OCH 2 CH 2 -cyclopentyl, —OCH 2 CH 2 -cyclohexyl,

—CH 2 OCH 2 CH 3 , —CH 2 OCH 2 CH 2 CH 3 , —CH 2 —OCH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH 3 , —CH 2 OCH 2 CH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 OCH 2 CH 2 CH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 O-cyclopropyl,

—CH 2 O-cyclobutyl, —CH 2 O-cyclopentyl,

—CH 2 O-cyclohexyl, —CH 2 OCH 2 -cyclopropyl,

—CH 2 OCH 2 -cyclobutyl, —CH 2 OCH 2 -cyclopentyl,

—CH 2 OCH 2 -cyclohexyl; —CH 2 (NH)CH 3 ,

—CH 2 (NH)CH 2 CH 3 , —CH 2 (NH)CH 2 CH 2 CH 3 , —CH 2 —(NH)CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH 3 , —CH 2 (NH)CH 2 CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 (NH)CH 2 CH 2 CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 (NH)-cyclopropyl,

—CH 2 (NH)-cyclobutyl, —CH 2 (NH)-cyclopentyl,

—CH 2 (NH)-cyclohexyl, —CH 2 (NH)CH 2 -cyclopropyl,

—CH 2 (NH)CH 2 -cyclobutyl, —CH 2 (NH)CH 2 -cyclopentyl,

or —CH 2 (NH)CH 2 -cyclohexyl;

W is a bond;

X is a bond;

Y is a bond;

Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, t-butyl, or allyl;

R 13 , at each occurrence, is independently selected from

F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , or —CF 3 .

10. A compound according to claim 9 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof

wherein:

Q is —(CH 2 ) m —R 4 ,

—(CH 2 ) n —s—R 4 ,

—(CH 2 ) n —O—R 4 , or

—(CH 2 ) m —N(H)—R 4 ;

m is 1 or 2;

n is 0 or 1;

R 4 is 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 ,

C 6 -C 10 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 , N 1 R 15 R 16 , CF 3 , C(═O)OR 22 , SR 22 , OR 22 , OR 14a , 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 H;

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;

Ring B is:

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 ;

C 6 -C 10 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 ;

W is a bond, —CH 2 —, —CH 2 CH 2 —;

X is a bond;

phenyl substituted with 0-2 R Xb ;

C 3 -C 6 cycloalkyl substituted with 0-2 R Xb ; or

5 to 6 membered heterocycle substituted with 0-2 R Xb ;

R Xb , at each occurrence, is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —,

—N(R 19 )—, —C(═O)NR 19b —, —NR 19b C(═O)—, —NR 19b S(O) 2 ,

—S(═O) 2 NR 19b , —NR 19b S(O)—, —S(═O)NR 19b —, —C(═O)O—,

or —OC(═O)—;

Z is C 1 -C 3 alkyl substituted with 1-2 R 12a ;

aryl substituted with 0-4 R 12b ;

C 3 -C 10 carbocycle substituted with 0-3 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

aryl substituted with 0-4 R 12b ;

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

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

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 4 alkyl)-C(═O)—, and (C 1 -C 4 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 4 alkyl)-C(═O)—, and (C 1 -C 4 alkyl)-S(═O) 2 —; and

alternatively, R 15 and R 16 , together with the nitrogen to

which they are attached, may combine to form a 4-6

membered ring wherein said 4-6 membered ring

optionally contains an additional heteroatom selected

from O or NH, wherein said 4-6 membered ring is

selected from imidazolidinyl, oxazolidinyl, thiazolidinyl, piperazinyl, morpholinyl, and thiomorpholinyl;

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, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

R 21 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl; and

R 22 is methyl, ethyl, propyl, butyl, propenyl, butenyl, and propargyl.

11. A compound according to claim 10 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof wherein:

Q is —CH 2 R 4 , —O—R 4 , or —CH 2 —NH—R 4 ;

R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ;

C 2 -C 6 alkenyl substituted with 0-3 R 4a ;

C 2 -C 6 alkynyl substituted with 0-3 R 4a ;

C 3 -C 6 carbocycle substituted with 0-3 R 4b ;

phenyl substituted with 0-3 R 4b , or

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;

R 4a , at each occurrence, is independently selected from H, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , C(═O)OR 22 , SR 22 , OR 14a , 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 H;

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

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

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

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

H, methyl, ethyl, propyl, butyl, CF 3 , Cl, F, Br, I, ═O;

C 3 -C 6 carbocycle substituted with 0-3 R 5c ;

phenyl substituted with 0-3 R 5c ; or

5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 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 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and

C 1 -C 2 haloalkoxy;

Ring B is:

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 ;

W is a bond, —CH 2 —, —CH 2 CH 2 —;

X is a bond;

phenyl substituted with 0-1 R Xb ;

C 3 -C 6 cycloalkyl substituted with 0-1 R Xb ; or

5 to 6 membered heterocycle substituted with 0-1 R Xb ;

R Xb is selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, and —OCF 3 ;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —NH—,

—N(CH 3 )—, or —N(CH 2 CH 3 )—;

Z is C 1 -C 2 alkyl substituted with 1-2 R 12a ;

aryl substituted with 0-4 R 12b ;

C 3 -C 10 carbocycle substituted with 0-3 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

aryl substituted with 0-4 R 12b ;

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

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

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 4 alkyl, or C 2 -C 4 alkoxyalkyl;

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 4 alkyl, and benzyl;

R 16 , at each occurrence, is independently selected from

H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O) 2 —, and ethyl-S(═O) 2 —;

R 18 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

R 19 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, and butyl; and

R 21 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl; and

R 22 is methyl, ethyl, propyl, butyl, propenyl, butenyl, and propargyl.

12. A compound according to claim 11 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof wherein:

Q is —CH 2 R 4 , —O—R 4 , or —CH 2 —NH—R 4 ;

R 4 is C 1 -C 6 alkyl substituted with 0-2 R 4a ,

C 2 -C 6 alkenyl substituted with 0-2 R 4a ,

C 2 -C 6 alkynyl substituted with 0-2 R 4a , or

C 3 -C 6 cycloalkyl substituted with 0-3 R 4b ;

R 4a , at each occurrence, is independently selected from is H, OH, F, Cl, Br, I, CN, NR 15 NR 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, OCF 3 ;

C 3 -C 6 carbocycle substituted with 0-3 R 4b ,

phenyl substituted with 0-3 R 4b , or

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 H;

C 1 -C 4 alkyl substituted with 0-1 R 5b ;

C 2 -C 4 alkenyl substituted with 0-i R 5b ; or

C 2 -C 4 alkynyl substituted with 0-1 R 5b ;

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

H, methyl, ethyl, propyl, butyl, CF 3 ;

C 3 -C 6 carbocycle substituted with 0-2 R 5c ;

phenyl substituted with 0-3 R 5c ; and

R 5c , at each occurrence, is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

Ring B is:

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 10a ;

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 ;

W is a bond or —CH 2 —;

X is a bond;

phenyl substituted with 0-1 R Xb ;

C 3 -C 6 cycloalkyl substituted with 0-1 R Xb ; or

5 to 6 membered heterocycle substituted with 0-1 R Xb ;

R Xb is selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, methyl, ethyl, methoxy, ethoxy, and —OCF 3 ;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —NH—,

—N(CH 3 )—, or —N(CH 2 CH 3 )—;

Z is C 1 -C 2 alkyl substituted with 1-2 R 12a ;

aryl substituted with 0-4 R 12b ;

C 3 -C 10 carbocycle substituted with 0-3 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

C 6 -C 10 aryl substituted with 0-4 R 12b ;

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

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

H, OH, Cl, F, N 1 R 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and —OCF 3 ;

R 13 , at each occurrence, is independently selected from

OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR 15 R 16 , and CF 3 ;

R 14 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl; and

R 16 , at each occurrence, is independently selected from

H, OH, methyl, ethyl, propyl, butyl, benzyl, and phenethyl;

R 18 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and

R 19 , at each occurrence, is independently selected from

H, methyl, ethyl, propyl, and butyl.

13. A compound according to claim 12 of Formula (Ib) or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

R 5 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(CH 3 ) 2 , —CH 2 N(CH 2 CH 3 ) 2 , —CH 2 CH 2 NH 2 , —CH 2 CH 2 N(CH 3 ) 2 , —CH 2 CH 2 N(CH 2 CH 3 ) 2 , —CH 2 -cyclopropyl, —CH 2 -cyclobutyl,

—CH 2 -cyclopentyl, —CH 2 -cyclohexyl,

—CH 2 CH 2 -cyclopropyl, —CH 2 CH 2 -cyclobutyl,

—CH 2 CH 2 -cyclopentyl, or —CH 2 CH 2 -cyclohexyl;

Q is —CH 3 , —CH 2 CH 3 , CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ,

—CH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 -cyclopropyl,

—CH 2 -cyclobutyl, —CH 2 -cyclopentyl, CH 2 -cyclohexyl,

—CH 2 CH 2 -cyclopropyl, —CH 2 CH 2 -cyclobutyl,

—CH 2 CH 2 -cyclopentyl, —CH 2 CH 2 -cyclohexyl,

—OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH(CH 3 ) 2 ,

—OCH 2 CH 2 CH 2 CH 3 , —OCH 2 CH(CH 3 ) 2 , —OCH 2 CH 2 CH(CH 3 ) 2 ,

—OCH 2 CH 2 CH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ,

—OCH 2 CH 2 CH 2 CH(CH 3 ) 2 , —OCH 2 CH 2 CH 2 CH 2 CH(CH 3 ) 2 ,

—OCH 2 -cyclopropyl, —OCH 2 -cyclobutyl,

—OCH 2 -cyclopentyl, —OCH 2 -cyclohexyl,

—OCH 2 CH 2 -cyclopropyl, OCH 2 CH 2 -cyclobutyl,

—OCH 2 CH 2 -cyclopentyl, —OCH 2 CH 2 -cyclohexyl,

—CH 2 OCH 2 CH 3 , —CH 2 OCH 2 CH 2 CH 3 , —CH 2 —OCH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH 3 , —CH 2 OCH 2 CH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 OCH 2 CH 2 CH(CH 3 ) 2 ,

—CH 2 OCH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 20 -cyclopropyl,

—CH 2 O-cyclobutyl, —CH 2 O-cyclopentyl,

—CH 2 O-cyclohexyl, —CH 2 OCH 2 -cyclopropyl,

—CH 2 OCH 2 -cyclobutyl, —CH 2 OCH 2 -cyclopentyl,

—CH 2 OCH 2 -cyclohexyl; —CH 2 (NH)CH 3 ,

—CH 2 (NH)CH 2 CH 3 , —CH 2 (NH)CH 2 CH 2 CH 3 , —CH 2 —(NH)CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH 3 , —CH 2 (NH)CH 2 CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 (NH)CH 2 CH 2 CH(CH 3 ) 2 ,

—CH 2 (NH)CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 (NH)-cyclopropyl,

—CH 2 (NH)-cyclobutyl, —CH 2 (NH)-cyclopentyl,

—CH 2 (NH)-cyclohexyl, —CH 2 (NH)CH 2 -cyclopropyl,

—CH 2 (NH)CH 2 -cyclobutyl, —CH 2 (NH)CH 2 -cyclopentyl,

or —CH 2 (NH)CH 2 -cyclohexyl;

W is a bond or —CH 2 —;

X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═0)—, —S(═0) 2 —, —NH—, or —N(CH 3 )—,

Z is phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl,

2,4-diF-phenyl, 2,5diF-phenyl, 2,6-diF-phenyl,

3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl,

2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,

3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,

3-F-5-C1-phenyl, 3-Cl-4-F-phenyl, 2-MeO-phenyl,

3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl,

4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF 3 O-phenyl, 3-CF 3 O-phenyl, 4-CF 3 O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl,

4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl,

1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino, N-piperinyl,

phenyl—CH 2 —, (2-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 —,

(4-F-phenyl)CH 2 —, (2-Cl-phenyl)CH 2 —, (3-Cl-phenyl)CH 2 , (4-Cl-phenyl)CH 2 —, (2,3-diF-phenyl)CH 2 —,

(2,4-diF-phenyl)CH 2 —, (2,5-diF-phenyl)CH 2 —,

(2,6-diF-phenyl)CH 2 —, (3,4-diF-phenyl)CH 2 —,

(3,5-diF-phenyl)CH 2 —, (2,3-diCl-phenyl)CH 2 —,

(2,4-diCl-phenyl)CH 2 —, (2,5-diC 1 -phenyl)CH 2 —,

(2,6-diCl-phenyl)CH 2 —, (3,4-diCl-phenyl)CH 2 —,

(3,5-diCl-phenyl)CH 2 —, (3-F-4-Cl-phenyl)CH 2 —,

(3-F-5-Cl-phenyl)CH 2 —, (3-Cl-4-F-phenyl)CH 2 —,

(2-MeO-phenyl)CH 2 —, (3-MeO-phenyl)CH 2 —,

(4-MeO-phenyl)CH 2 —, (2-Me-phenyl)CH 2 —,

(3-Me-phenyl)CH 2 —, (4-Me-phenyl)CH 2 —,

(2-MeS-phenyl)CH 2 —, (3-MeS-phenyl)CH 2 —,

(4-MeS-phenyl)CH 2 —, (2-CF 3 O-phenyl)CH 2 —,

(3-CF 3 O-phenyl)CH 2 —, (4-CF 3 O-phenyl)CH 2 —,

(furanyl)CH 2 —, (thienyl)CH 2 —, (pyridyl)CH 2 —,

(2-Me-pyridyl)CH 2 —, (3-Me-pyridyl)CH 2 —,

(4-Me-pyridyl)CH 2 —, (1-imidazolyl)CH 2 —,

(oxazolyl)CH 2 —, (isoxazolyl)CH 2 —,

(1-benzimidazolyl)CH 2 —, (cyclopropyl)CH 2 —, (cyclobutyl)CH 2 —, (cyclopentyl)CH 2 —,

(cyclohexyl)CH 2 —, (morpholino)CH 2 —,

(N-pipridinyl)CH 2 —, or (phenyl) 2 CH—;

R 10 is selected from:

H, ═O, methyl, ethyl, phenyl, benzyl, phenethyl,

4-F-phenyl, (4-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 CH 2 —,

3-F-phenyl, (3-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 CH 2 —,

2-F-phenyl, (2-F-phenyl)CH 2 —, (2-F-phenyl)CH 2 CH 2 —,

4-Cl-phenyl, (4-Cl-phenyl)CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —,

3-Cl-phenyl, (3-Cl-phenyl)CH 2 —, (3-Cl-phenyl)CH 2 CH 2 —,

4-CH 3 -phenyl, (4-CH 3 -phenyl)CH 2 —, (4-CH 3 -phenyl)CH 2 CH 2 —,

3-CH 3 -phenyl, (3-CH 3 -phenyl)CH 2 —, (3-CH 3 -phenyl)CH 2 CH 2 —,

4-CF 3 -phenyl, (4-CF 3 -phenyl)CH 2 —, (4-CF 3 -phenyl)CH 2 CH 2 —,

pyrid-2-yl, 4-F-pyrid-2-yl, 4-Cl-pyrid-2-yl,

4-CH 3 -pyrid-2-yl, 4-CF 3 -pyrid-2-yl, pyrid-3-yl,

4-F-pyrid-3-yl, 4-Cl-pyrid-3-yl, 4-CH 3 -pyrid-3-yl,

4-CF 3 -pyrid-3-yl, and pyrid-4-yl; and

R 13 , at each occurrence, is independently selected from

F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , and —CF 3 .

14. A compound according to one of claim 5 of Formula (Ib):

or a stereoisomer, or a pharmaceutically acceptable salt thereof; R 13 is selected from F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , and —CF 3 .

15. A pharmaceutical composition comprising a compound of claim 2 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising a compound of claim 5 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

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

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

19. A pharmaceutical composition comprising a compound of claim 8 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising a compound of claim 9 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

21. A pharmaceutical composition comprising a compound of claim 10 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising a compound of claim 11 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising a compound of claim 12 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising a compound of claim 13 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising a compound of claim 14 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

26. 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 2 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

27. 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 5 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

28. 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 a pharmaceutically acceptable salt thereof.

29. 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 7 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

30. 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 8 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

31. 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 9 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

32. 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 10 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

33. 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 11 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

34. 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 12 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

35. 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 13 , or a stereoisomer or a pharmaceutically acceptable salt thereof.

36. 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 14 , or a stereoisomer or a pharmaceutically acceptable salt thereof.