US2003130251A1PendingUtilityA1
Amino lactam sulfonamides as inhibitors of A-beta protein production
Priority: Oct 8, 1999Filed: Nov 4, 2002Published: Jul 10, 2003
Est. expiryOct 8, 2019(expired)· nominal 20-yr term from priority
C07D 409/14C07D 417/12C07D 243/10C07D 405/12C07D 409/12C07D 413/12C07D 401/12C07D 243/24A61P 25/28
47
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Claims
Abstract
This invention relates to novel lactams having the Formula (I): to their pharmaceutical compositions and to their 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
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of the Formula (I):
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
Q is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1b ;
C 3 -C 10 carbocycle substituted with 0-3 R 1b ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1a , at each occurrence, is independently selected from H, R 1b , Cl, F, Br, I, OR 14 , CN, NO 2 , ═O, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl; C 2 -C 4 alkenyl; C 2 -C 4 alkynyl; C 1 -C 4 haloalkyl; C 1 -C 4 haloalkoxy;
C 3 -C 10 carbocycle substituted with 0-3 R 1b ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1b , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, I, CN, NO 2 , ═O, NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
—C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
C 2 -C 6 alkenyl substituted with 0-2 R 1c ;
C 2 -C 6 alkynyl substituted with 0-2 R 1c ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; and
5 to 14 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 14 membered heterocycle is substituted with 0-3 R 1f ;
R 1c , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, I, CN, NO 2 , NR 19 R 20 , CF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
—C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , NR 19b s(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; 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 1f ;
R 1d , at each occurrence, is independently selected from H,
C 1 -C 6 alkyl substituted with 0-3 R 1e ;
C 2 -C 6 alkenyl substituted with 0-2 R 1e ;
C 2 -C 6 alkynyl substituted with 0-2 R 1e ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; 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 1f ;
R 1e , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, I, CN, NO 2 , ═O, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; 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 1f ;
R 1f , at each occurrence, is independently selected from H, OR 14 , SR 14 , Cl, F, Br, I, CN, NO 2 , ═O, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
R 2 is H, C 1 -C 6 alkyl, (C 1 -C 6 alkoxy) C 1 -C 3 alkyl, C 3 -C 6 carbocycle, C 6 -C 10 aryl, (C 3 -C 6 carbocycle)methyl, (C 6 -C 10 aryl)methyl, (C 6 -C 10 aryl)ethyl, or 5 to 10 membered heterocycle;
R 5 is H, OR 14 ;
C 1 -C 6 alkyl substituted with 0-3 R 5b ;
C 1 -C 6 alkoxy 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 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 10 carbocycle substituted with 0-3 R 5c ;
C 6 -C 10 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 5a is H or C 1 -C 4 alkyl;
R 5b , at each occurrence, is independently selected from:
H, C 1 -C 6 alkyl, CF 3 , OR 14 , Cl, F, Br, I, ═O, CN, NO 2 , NR 15 R 16 ; acetyl, —S(C 1 -C 4 alkyl), —S(═O)(C 1 -C 4 alkyl), —S(═O) 2 (C 1 -C 4 alkyl);
C 3 -C 10 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 10 carbocycle substituted with 0-3 R 5c ;
C 6 -C 10 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 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, 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
C 6 -C 10 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;
Ring B is a 6, 7, or 8 membered lactam,
wherein the lactam is saturated, partially saturated or unsaturated;
wherein each additional lactam carbon is substituted with 0-2 R 11 ; and,
optionally, the lactam contains a heteroatom selected from —N═, —NH—, —N(R 10 )—, —O—, —S—, —S(═O)—, and —S(═O) 2 —;
additionally, two R 11 substituents on adjacent atoms may be combined to form C 3 -C 6 carbocycle fused radical, a benzo fused radical, or a 5 to 6 membered heteroaryl fused radical,
wherein said 5 to 6 membered heteroaryl fused radical comprises 1-2 heteroatoms selected from N, O, and S;
wherein said benzo fused radical or 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 13 ;
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 substituted with 0-2 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 ;
R 10b , 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 , 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 11 , at each occurrence, is independently selected from
H, C 1 -C 4 alkoxy, Cl, F, Br, I, ═O, CN, NO 2 , NR 18 R 19 , C(═O)R 17 , C(═O)OR 17 , C(═O)NR 18 R 19 , S(═O) 2 NR 18 R 19 , CF 3 ;
C 1 -C 6 alkyl substituted with 0-1 R 11a ;
C 6 -C 10 aryl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11a , 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 phenyl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11b , 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 —(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;
C 6 -C 10 aryl substituted with 0-3 R Xb ;
C 3 -C 10 cycloalkyl substituted with 0-3 R Xb ;
C 3 -C 10 carbocycle substituted with 0-3 R Xb ; 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 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 haloalkyl-S—;
Y is a bond or —(CR 9 R 9a ) t —V—(CR 9 R 9a ) u —;
t is 0, 1, 2, or 3;
u is 0, 1, 2, or 3;
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 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
C 6 -C 10 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 12 is C 6 -C 10 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 H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , or CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl;
R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 16 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
alternatively, —NR 15 R 16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R 17 is H, aryl, aryl-CH 2 —, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl;
R 18 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 19 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 19b , at each occurrence, is independently selected from H, C 1 -C 4 alkyl, phenyl, benzyl, and phenethyl; and
R 20 and R 21 , at each occurrence, are independently selected from H, C 1 -C 4 alkyl, aryl, and aryl(C 1 -C 2 alkyl)-;
provided that when Q is phenyl, 3-F-phenyl, benzyl, propyl, or octyl; R 2 is H; R 5 is methyl, and -WXYZ is methyl, then Ring B is not
wherein R 13 is H.
2 . A compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof, wherein:
Q is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1b ;
C 3 -C 10 carbocycle substituted with 0-3 R 1b ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1a , at each occurrence, is independently selected from H, R 1b , Cl, F, Br, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl;
C 3 -C 10 carbocycle substituted with 0-3 R 1b ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1b , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
—C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; and
5 to 14 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 14 membered heterocycle is substituted with 0-3 R 1f ;
R 1c , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; —C(═O)—R 1d , —O—R 1d , —S—R 1d ,
—S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; 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 1f ;
R 1d , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl substituted with 0-3 R 1f ; R 1f , at each occurrence, is independently selected from H, OR 14 , SR 14 , Cl, F, Br, I, CN, NO 2 , ═O, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—; R 2 is H or C 1 -C 6 alkyl; R 5 is H, OR 14 ;
C 1 -C 6 alkyl substituted with 0-3 R 5b ;
C 1 -C 6 alkoxy 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 5a is H or C 1 -C 4 alkyl; R 5b , at each occurrence, is independently selected from:
H, C 1 -C 6 alkyl, CF 3 , OR 14 , Cl, F, Br, I, ═O, CN, NO 2 , NR 15 R 16 ; acetyl, S(C 1 -C 4 alkyl), S(═O)(C 1 -C 4 alkyl), S(═O) 2 (C 1 -C 4 alkyl),
C 3 -C 10 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 10 carbocycle substituted with 0-3 R 5c ;
C 6 -C 10 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, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—; R 6 is H, methyl, or ethyl; Ring B is a seven membered lactam,
wherein the lactam is saturated, partially saturated or unsaturated;
wherein each additional lactam carbon is substituted with 0-2 R 11 ; and,
optionally, the lactam contains a heteroatom selected from —N═, —NH—, —N(R 10 )—, —O—, —S—, —S(═O)—, and —S(═O) 2 —;
additionally, two R 11 substituents on adjacent atoms may be combined to form C 3 -C 6 carbocycle fused radical, a benzo fused radical, or a 5 to 6 membered heteroaryl fused radical,
wherein said 5 to 6 membered heteroaryl fused radical comprises 1-2 heteroatoms selected from N, O, and S;
wherein said benzo fused radical or 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 13 ;
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 substituted with 0-2 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 ; R 10b , 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 , 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 11 , at each occurrence, is independently selected from
H, C 1 -C 4 alkoxy, Cl, F, Br, I, ═O, CN, NO 2 , NR 18 R 19 , C(═O)R 17 , C(═O)OR 17 , C(═O)NR 18 R 19 , S(═O) 2 NR 18 R 19 , CF 3 ;
C 1 -C 6 alkyl substituted with 0-1 R 11a ;
C 6 -C 10 aryl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11a , 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 phenyl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11b , 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 —(CR 8 R 8a ) p —; p is 0, 1, or 2; R 8 and R 8a , at each occurrence, are independently selected from H, F, methyl, and ethyl; X is a bond;
phenyl substituted with 0-3 R Xb ;
C 3 -C 6 cycloalkyl substituted with 0-3 R Xb ; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is 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 haloalkyl-S—; 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, methyl, and ethyl; V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —NHC(═O)—, or —C(═O)NH—; Z is H;
C 1 -C 6 alkyl substituted with 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 12 is phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 H, OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ; R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 6 alkyl, and C 2 -C 6 alkoxyalkyl; R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl); R 16 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl); alternatively, —NR 15 R 16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; R 17 is H, aryl, aryl-CH 2 —, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl; R 18 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl); R 19 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl); and R 20 is H or C 1 -C 4 ; provided that when Q is phenyl, 3-F-phenyl, benzyl, propyl, or octyl; R 2 is H; R 5 is methyl, and -WXYZ is methyl, then Ring B is not wherein R 13 is H.
3 . A compound of claim 2 wherein Ring B is selected from:
wherein each benzo fused radical is substituted with 0-3 R 13 .
4 . A compound of claim 3 of Formula (I):
or a pharmaceutically acceptable salt form or prodrug thereof, wherein:
Q is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1b ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1a , at each occurrence, is independently selected from H, Cl, F, Br, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl; C 1 -C 4 haloalkyl;
C 6 -C 10 aryl substituted with 0-3 R 1b ; 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 1b ;
R 1b , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
—C(═O)—R 1d , —OR 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; and
5 to 14 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 14 membered heterocycle is substituted with 0-3 R 1f ;
R 1c , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; —C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 3 -C 10 cycloalkyl substituted with 0-3 R 1f ;
C 3 -C 10 carbocycle substituted with 0-3 R 1f ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; 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 1f ;
R 1d , at each occurrence, is independently selected from
H, C 1 -C 6 alkyl, and
C 6 -C 10 aryl substituted with 0-3 R 1f ;
R 1f , at each occurrence, is independently selected from
H, Cl, F, Br, NO 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and
C 1 -C 4 haloalkyl-S—;
R 2 is H, methyl, or ethyl;
R 5 is OR 14 ;
C 1 -C 6 alkyl substituted with 0-3 R 5b ;
C 1 -C 6 alkoxy 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 5a is H or C 1 -C 4 alkyl;
R 5b , at each occurrence, is independently selected from:
H, C 1 -C 6 alkyl, CF 3 , OR 14 , Cl, F, Br, I, ═O, CN, NO 2 , NR 15 R 16 , acetyl, —S(C 1 -C 4 alkyl), S(═O)(C 1 -C 4 alkyl), S(═O) 2 (C 1 -C 4 alkyl);
C 3 -C 10 cycloalkyl substituted with 0-3 R 5c ;
C 6 -C 10 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, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
R 6 is H;
Ring B is selected from:
R 11 , at each occurrence, is independently selected from
H, C 1 -C 4 alkoxy, Cl, F, Br, I, ═O, CN, NO 2 , NR 18 R 19 , C(═O)R 17 , C(═O)OR 17 , C(═O)NR 18 R 19 , S(═O) 2 NR 18 R 19 , CF 3 ;
C 1 -C 6 alkyl substituted with 0-1 R 11a ;
C 6 -C 10 aryl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11a , 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 , phenyl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11b , 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 —(CR 8 R 8a ) p —;
p is 0, 1, or 2;
R 8 and R 8a , at each occurrence, are independently selected from H, F, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 R Xb ;
C 3 -C 6 cycloalkyl substituted with 0-3 R Xb ; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is 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 haloalkyl-S—;
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, methyl, and ethyl;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)NH—, or —NHC(═O)—;
Z is H;
C 1 -C 6 alkyl substituted with 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 12 is phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 H, OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, CN, NO 2 , and CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl;
R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 16 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
alternatively, —NR 15 R 16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R 17 is H, aryl, aryl-CH 2 —, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl;
R 18 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 19 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl); and
R 20 is H or C 1 -C 4 ;
provided that when Q is phenyl, 3-F-phenyl, benzyl, propyl, or octyl; R 2 is H; R 5 is methyl, and -WXYZ is methyl, then Ring B is not
wherein R 13 is H.
5 . A compound of claim 4 of Formula (Ia):
or a pharmaceutically acceptable salt form or prodrug thereof, wherein:
Ring B is
Q is C 1 -C 6 alkyl substituted with 0-2 R 1a ;
C 6 -C 10 aryl substituted with 0-3 R 1b ; or
5 to 10 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 1b ;
R 1a , at each occurrence, is independently selected from H, Cl, F, Br, NR 19 R 20 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and phenyl substituted with 0-3 R 1b ;
R 1b , at each occurrence, is independently selected from H, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; —C(═O)—R 1d , —O—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
C 6 -C 10 aryl substituted with 0-3 R 1f ; and
5 to 14 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 14 membered heterocycle is substituted with 0-3 R 1f ;
R 1c , at each occurrence, is independently selected from H, —C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —NR 19b S(═O)—R 1d , —S(═O)NR 19b —R 1d , —C(═O)O—R 1d , and —OC(═O)—R 1d ;
R 1d , at each occurrence, is independently selected from
H, C 1 -C 6 alkyl, and
C 6 -C 10 aryl substituted with 0-3 R 1f ;
R 1f , at each occurrence, is independently selected from H, Cl, F, Br, NO 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
R 5 is OR 14 ;
C 1 -C 6 alkyl substituted with 0-1 R 5b ;
C 2 -C 6 alkenyl substituted with 0-1 R 5b ; or
C 2 -C 6 alkynyl substituted with 0-1 R 5b ;
R 5a is H or C 1 -C 4 alkyl;
R 5b , at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF 3 , OR 14 , Cl, F, Br, I, ═O, CN, NO 2 , NR 15 R 16 ; acetyl, —S(C 1 -C 4 alkyl), —S(═O)(C 1 -C 4 alkyl), —S(═O) 2 (C 1 -C 4 alkyl),
C 3 -C 7 cycloalkyl substituted with 0-3 R 5c ;
phenyl substituted with 0-3 R 5c ; and
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 5c ;
R 5c , at each occurrence, is independently selected from H, OH, Cl, F, —NR 15 R 16 , CF 3 , acetyl, SCH 3 , S(═O) 2 CH 3 , methyl, ethyl, propyl, butyl, metrhoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
R 11 , at each occurrence, is independently selected from
H, —NR 18 R 19 , —C(═O)R 17 , —C(═O)OR 17 , —C(═O)NR 18 R 19 , —S(═O) 2 NR 18 R 19 , —CF 3 ;
C 1 -C 6 alkyl substituted with 0-1 R 11a ;
phenyl substituted with 0-3 R 11b ;
C 3 -C 6 carbocycle substituted with 0-3 R 11b ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ;
R 11a , at each occurrence, is independently selected from H, C 1 -C 4 alkyl, OR 14 , Cl, F, Br, CN, NO 2 , NR 15 R 16 , CF 3 , phenyl substituted with 0-3 R 11b ;
C 3 -C 10 carbocycle substituted with 0-3 R 11b ; 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 11b ;
R 11b , 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 —(CR 8 R 8a ) p —;
p is 0, 1, or 2;
R 8 and R 8a , at each occurrence, are independently selected from H, F, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 R Xb ;
C 3 -C 6 cycloalkyl substituted with 0-3 R Xb ; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is 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 haloalkyl-S—;
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, methyl, and ethyl;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)NH—, or —NHC(═O)—;
Z is H;
C 1 -C 6 alkyl substituted with 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 12 is phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 H, OH, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, Cl, F, Br, CN, NO 2 , and CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 6 alkyl, and C 2 -C 6 alkoxyalkyl;
R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 16 , at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
alternatively, —NR 15 R 16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R 17 is H, phenyl, benzyl, C 1 -C 4 alkyl, or C 2 -C 4 alkoxyalkyl;
R 18 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C 1 -C 6 alkyl) and —S(═O) 2 —(C 1 -C 6 alkyl);
R 19 , at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and
R 20 is H, methyl, ethyl, propyl, or butyl.
6 . A compound of claim 5 of Formula (Ia) wherein:
Ring B is
Q is C 1 -C 6 alkyl substituted with 0-1 R 1a ;
phenyl substituted with 0-3 R 1b ;
naphthyl substituted with 0-3 R 1b ; or
5 to 10 membered heterocycle containing 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 1b ;
R 1a , at each occurrence, is independently selected from
H, Cl, F, Br, —NR 19 R 20 , —CF 3 ; and
phenyl substituted with 0-3 R 1b ;
R 1b , at each occurrence, is independently selected from H, methyl, ethyl, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy;
—C(═O)—R 1d , —O—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
phenyl substituted with 0-3 R 1f ; 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 1f ;
R 1c , at each occurrence, is independently selected from H, —C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , and —S(═O) 2 NR 19b —R 1d ;
R 1d , at each occurrence, is independently selected from H, C 1 -C 6 alkyl; and phenyl substituted with 0-3 R 1f ;
R 1f , at each occurrence, is independently selected from H, Cl, F, Br, NO 2 , CF 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
R 5 is OR 14 or C 1 -C 4 alkyl substituted with 0-1 R 5b ;
R 5a is H;
R 5b , at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, —NR 15 R 16 ;
C 3 -C 7 cycloalkyl substituted with 0-3 R 5c ;
phenyl substituted with 0-3 R 5c ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 5c ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, 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 , acetyl, SCH 3 , S(═O) 2 CH 3 , methyl, and methoxy;
R 11 , at each occurrence, is independently selected from
H, NR 18 R 19 , CF 3 ;
C 1 -C 6 alkyl substituted with 0-1 R 11a ;
phenyl substituted with 0-3 R 11b ;
C 3 -C 6 carbocycle substituted with 0-3 R 11b ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R 11a , at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NO 2 , NR 15 R 16 , CF 3 , phenyl substituted with 0-3 R 11b ;
C 3 -C 6 carbocycle substituted with 0-3 R 11b ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R 11b , 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;
W is —(CHR 8 ) p —;
p is 0 or 1;
R 8 is H, methyl, or ethyl;
X is a bond;
phenyl substituted with 0-2 R Xb ;
C 3 -C 6 cycloalkyl substituted with 0-3 R Xb ; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-1 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 haloalkyl-S—;
Y is a bond, —V—, —CH 2 —V—, —V—CH 2 —, or —CH 2 —V—CH 2 —;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)NH—, or —NHC(═O)—;
Z is H;
C 1 -C 6 alkyl substituted with 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 12 is phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 H, methyl, ethyl, methoxy, ethoxy, Cl, F, Br, NO 2 , or CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 4 alkyl, or C 2 -C 4 alkoxyalkyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R 16 , at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, CH 3 CH 2 C(═O)—, CH 3 C(═O)—, CH 3 CH 2 OC(═O)—, CH 3 OC(═O)—, CH 3 CH 2 S(═O) 2 — and CH 3 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, OH, methyl, ethyl, propyl, and butyl; and
R 20 is H, methyl, ethyl, propyl, or butyl.
7 . A compound of claim 6 of Formula (Ia) wherein:
Ring B is
Q is C 1 -C 4 alkyl substituted with 0-1 R 1a ;
phenyl substituted with 0-3 R 1b ;
naphthyl substituted with 0-3 R 1b ; or
5 to 10 membered heterocycle containing 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 1b ; wherein said 5 to 10 membered heterocycle is selected from pyridinyl, quinolinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, imidazolyl, oxazolyl, and isoxazolyl;
R 1a , at each occurrence, is independently selected from
H, Cl, F, Br, CF 3 , and
phenyl substituted with 0-3 R 1b ;
R 1b , at each occurrence, is independently selected from H, methyl, ethyl, OR 14 , Cl, F, Br, NO 2 , NR 19 R 20 , CF 3 , OCF 3 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; —C(═O)—R 1d , —O—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , —NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , —S(═O) 2 NR 19b —R 1d , —C(═O)O—R 1d , —OC(═O)—R 1d ;
C 1 -C 6 alkyl substituted with 0-3 R 1c ;
phenyl substituted with 0-3 R 1f ; and
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 1f ;
R 1c , at each occurrence, is independently selected from H, —C(═O)—R 1d , —O—R 1d , —S—R 1d , —S(═O)—R 1d , —S(═O) 2 —R 1d , —N(R 19 )—R 1d , —C(═O)NR 19b R 1d , NR 19b C(═O)—R 1d , —NR 19b S(═O) 2 —R 1d , and —S(═O) 2 NR 19b —R 1d ,
R 1d , at each occurrence, is independently selected from H, C 1 -C 6 alkyl; and phenyl substituted with 0-3 R 1f ;
R 1f , at each occurrence, is independently selected from H, Cl, F, Br, NO 2 , CF 3 , —OCF 3 , methyl, ethyl, methoxy, and ethoxy;
R 5 is methyl substituted with 0-1 R 5b ;
ethyl substituted with 0-1 R 5b ;
propyl substituted with 0-1 R 5b ; or
butyl substituted with 0-1 R 5b ;
R 5a is H;
R 5b , at each occurrence, is independently selected from:
H, methyl, ethyl, and NR 15 R 16 ;
R 11 , at each occurrence, is independently selected from H, NR 18 R 19 , CF 3 ;
C 1 -C 4 alkyl substituted with 0-1 R 11a ;
phenyl substituted with 0-3 R 11b ;
C 3 -C 6 carbocycle substituted with 0-3 R 11b ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R 11a , at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, NR 15 R 16 , CF 3 ;
phenyl substituted with 0-3 R 11b ;
C 3 -C 6 carbocycle substituted with 0-3 R 11b ; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R 11b , at each occurrence, is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, methoxy, and ethoxy;
W is a bond, —CH 2 —, or —CH(CH 3 )—;
X is a bond;
phenyl substituted with 0-1 R Xb ;
C 3 -C 6 cycloalkyl substituted with 0-3 R Xb ; 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 selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, and isoxazolyl;
Y is a bond, —V—, —CH 2 —V—, or —V—CH 2 —;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 19 )—, —C(═O)NH—, or —NHC(═O)—;
Z is H;
C 1 -C 6 alkyl substituted with 0-2 R 12 ;
C 2 -C 6 alkenyl substituted with 0-2 R 12 ;
C 2 -C 6 alkynyl substituted with 0-2 R 12 ;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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 12 is phenyl substituted with 0-4 R 12b ;
C 3 -C 6 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, NR 15 R 16 , CF 3 , OCF 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 H, methyl, methoxy, Cl, F, Br, and CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, methyl, ethyl, propyl, and butyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, or butyl;
R 16 , at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
(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 —, morpholino)CH 2 —, (N-piperidinyl)CH 2 —, phenyl-CH 2 CH 2 —, (phenyl) 2 CHCH 2 —, (2-F-phenyl)CH 2 CH 2 —, (3-F-phenyl)CH 2 CH 2 —, (4-F-phenyl)CH 2 CH 2 —, (2-Cl-phenyl)CH 2 CH 2 —, (3-Cl-phenyl)CH 2 CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, (2,3-diF-phenyl)CH 2 CH 2 —, (2,4-diF-phenyl)CH 2 CH 2 —, (2,5-diF-phenyl)CH 2 CH 2 —, (2,6-diF-phenyl)CH 2 CH 2 —, (3,4-diF-phenyl)CH 2 CH 2 —, (3,5-diF-phenyl)CH 2 CH 2 —, (2,3-diCl-phenyl)CH 2 CH 2 —, (2,4-diCl-phenyl)CH 2 CH 2 —, (2,5-diCl-phenyl)CH 2 CH 2 —, (2,6-diCl-phenyl)CH 2 CH 2 —, (3,4-diCl-phenyl)CH 2 CH 2 —, (3,5-diCl-phenyl)CH 2 CH 2 —, (3-F-4-Cl-phenyl)CH 2 CH 2 —, (3-F-5-Cl-phenyl)CH 2 CH 2 —, (3-Cl-4-F-phenyl)CH 2 CH 2 —, (2-MeO-phenyl)CH 2 CH 2 —, (3-MeO-phenyl)CH 2 CH 2 —, (4-MeO-phenyl)CH 2 CH 2 —, (2-Me-phenyl)CH 2 CH 2 —, (3-Me-phenyl)CH 2 CH 2 —, (4-Me-phenyl)CH 2 CH 2 —, (2-MeS-phenyl)CH 2 CH 2 —, (3-MeS-phenyl)CH 2 CH 2 —, (4-MeS-phenyl)CH 2 CH 2 —, (2-CF 3 O-phenyl)CH 2 CH 2 —, (3-CF 3 O-phenyl)CH 2 CH 2 —, (4-CF 3 O-phenyl)CH 2 CH 2 —, (furanyl)CH 2 CH 2 —, (thienyl)CH 2 CH 2 —, (pyridyl)CH 2 CH 2 —, (2-Me-pyridyl)CH 2 CH 2 —, (3-Me-pyridyl)CH 2 CH 2 —, (4-Me-pyridyl)CH 2 CH 2 —, (imidazolyl)CH 2 CH 2 —, (oxazolyl)CH 2 CH 2 —, (isoxazolyl)CH 2 CH 2 —, (benzimidazolyl)CH 2 CH 2 —,(cyclopropyl)CH 2 CH 2 —, (cyclobutyl)CH 2 CH 2 —, (cyclopentyl)CH 2 CH 2 —, (cyclohexyl)CH 2 CH 2 —, (morpholino)CH 2 CH 2 —, or (N-piperidinyl)CH 2 CH 2 —;
R 11 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 4-F-phenyl, 4-Cl-phenyl, 4-CH 3 -phenyl, 4-CF 3 -phenyl, 4-CH 3 O-phenyl, 4-CF 3 O-phenyl, 3-F-phenyl, 3-Cl-phenyl, 3-CH 3 -phenyl, 3-CF 3 -phenyl, 3-CH 3 O-phenyl, 3-CF 3 O-phenyl, 2-F-phenyl, 2-Cl-phenyl, 2-CH 3 -phenyl, 2-CF 3 -phenyl, 2-CH 3 O-phenyl, 2-CF 3 O-phenyl, (4-F-phenyl)methyl-, (4-Cl-phenyl)methyl-,
(4-CH 3 -phenyl)methyl-, (4-CF 3 -phenyl)methyl-, (4-CH 3 O-phenyl)methyl-, (4-CF 3 O-phenyl)methyl-, (3-F-phenyl)methyl-, (3-Cl-phenyl)methyl-, (3-CH 3 -phenyl)methyl-, (3-CF 3 -phenyl)methyl-, (3-CH 3 O-phenyl)methyl-, (3-CF 3 O-phenyl)methyl-, (2-F-phenyl)methyl-, (2-Cl-phenyl)methyl-, (2-CH 3 -phenyl)methyl-, (2-CF 3 -phenyl)methyl-, (2-CH 3 O-phenyl)methyl-, (2-CF 3 O-phenyl)methyl-, 2-pyridyl-, 3-pyridyl-, 4-pyridyl-, 1-piperidinyl, 1-homopiperidinyl, and 1-morpholino; and
R 13 , at each occurrence, is independently selected from H, F, Cl, and methoxy.
9 . A compound of claim 7 wherein:
Q is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , phenyl-, 2-F-phenyl-, 2-Cl-phenyl-, 2-Br-phenyl-, 2-NO 2 -phenyl-, 2-CH 3 -phenyl-, 2-CH 3 CH 2 -phenyl-, 2-CH 3 O-phenyl-, 2-CF 3 -phenyl-, 2-CF 3 O-phenyl-, 2-CH 3 CONH-phenyl, or 3,5-dimethyl-isoxazol-4-yl-;
R 5 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 )CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 )CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH(CH 2 CH 3 ) 2 ,
W is a bond, —CH 2 —, or —CH(CH 3 )—;
X is a bond;
Y is a bond, —CH 2 —V—, —V—, or —V—CH 2 —;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, —NH—, —N(CH 3 )—, —C(═O)NH—, or —NHC(═O)—,
Z is H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —C(CH 3 ) 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 )CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 )CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH(CH 2 CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —C(CH 3 ) 2 CH 2 CH 3 ,
—CH(CH 3 )CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 )CH 2 CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 )CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 )CH 2 CH 3 , —CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH(CH 2 CH 3 ) 2 ,
—CH 2 CH 2 C(CH 3 ) 3 , —CH(CH 2 CH 3 )CH 2 CH 2 CH 3 , —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CH 2 CF 3 ,
cyclopropyl-, (cyclopropyl)CH 2 —, (cyclopropyl)CH 2 CH 2 —, cyclobutyl-, (cyclobutyl)CH 2 —, (cyclobutyl)CH 2 CH 2 —, cyclopentyl-, (cyclopentyl)CH 2 —, (cyclopentyl)CH 2 CH 2 —, cyclohexyl-, (cyclohexyl)CH 2 —, (cyclohexyl)CH 2 CH 2 —, 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, 2,5-diF-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-Cl-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, morpholino, N-piperidinyl, 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-diCl-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 —, morpholino)CH 2 —, (N-piperidinyl)CH 2 —, phenyl-CH 2 CH 2 —, (phenyl) 2 CHCH 2 —, (2-F-phenyl)CH 2 CH 2 —, (3-F-phenyl)CH 2 CH 2 —, (4-F-phenyl)CH 2 CH 2 —, (2-Cl-phenyl)CH 2 CH 2 —, (3-Cl-phenyl)CH 2 CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, (2,3-diF-phenyl)CH 2 CH 2 —, (2,4-diF-phenyl)CH 2 CH 2 —, (2,5-diF-phenyl)CH 2 CH 2 —, (2,6-diF-phenyl)CH 2 CH 2 —, (3,4-diF-phenyl)CH 2 CH 2 —, (3,5-diF-phenyl)CH 2 CH 2 —, (2,3-diCl-phenyl)CH 2 CH 2 —, (2,4-diCl-phenyl)CH 2 CH 2 —, (2,5-diCl-phenyl)CH 2 CH 2 —, (2,6-diCl-phenyl)CH 2 CH 2 —, (3,4-diCl-phenyl)CH 2 CH 2 —, (3,5-diCl-phenyl)CH 2 CH 2 —, (3-F-4-Cl-phenyl)CH 2 CH 2 —, (3-F-5-Cl-phenyl)CH 2 CH 2 —, (3-Cl-4-F-phenyl)CH 2 CH 2 —, (2-MeO-phenyl)CH 2 CH 2 —, (3-MeO-phenyl)CH 2 CH 2 —, (4-MeO-phenyl.)CH 2 CH 2 —, (2-Me-phenyl)CH 2 CH 2 —, (3-Me-phenyl)CH 2 CH 2 —, (4-Me-phenyl)CH 2 CH 2 —, (2-MeS-phenyl)CH 2 CH 2 —, (3-MeS-phenyl)CH 2 CH 2 —, (4-MeS-phenyl)CH 2 CH 2 —, (2-CF 3 O-phenyl)CH 2 CH 2 —, (3-CF 3 O-phenyl)CH 2 CH 2 —, (4-CF 3 O-phenyl)CH 2 CH 2 —, (furanyl)CH 2 CH 2 —, (thienyl)CH 2 CH 2 —, (pyridyl)CH 2 CH 2 —, (2-Me-pyridyl)CH 2 CH 2 —, (3-Me-pyridyl)CH 2 CH 2 —, (4-Me-pyridyl)CH 2 CH 2 —, (imidazolyl)CH 2 CH 2 —, (oxazolyl)CH 2 CH 2 —, (isoxazolyl)CH 2 CH 2 —, (benzimidazolyl)CH 2 CH 2 —, (cyclopropyl)CH 2 CH 2 —, (cyclobutyl)CH 2 CH 2 —, (cyclopentyl)CH 2 CH 2 —, (cyclohexyl)CH 2 CH 2 —, (morpholino)CH 2 CH 2 —, or (N-piperidinyl)CH 2 CH 2 —;
R 11 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 4-F-phenyl, 4-Cl-phenyl, 4-CH 3 -phenyl, 4-CF 3 -phenyl, 4-CH 3 O-phenyl, 4-CF 3 O-phenyl, 3-F-phenyl, 3-Cl-phenyl, 3-CH 3 -phenyl, 3-CF 3 -phenyl, 3-CH 3 O-phenyl, 3-CF 3 O-phenyl, 2-F-phenyl, 2-Cl-phenyl, 2-CH 3 -phenyl, 2-CF 3 -phenyl, 2-CH 3 O-phenyl, 2-CF 3 O-phenyl, (4-F-phenyl)methyl-, (4-Cl-phenyl)methyl-,
(4-CH 3 -phenyl) methyl-, (4CF 3 -phenyl) methyl-, (4-CH 3 O-phenyl)methyl-, (4-CF 3 O-phenyl)methyl-, (3-F-phenyl)methyl-, (3-Cl-phenyl)methyl-, (3-CH 3 -phenyl)methyl-, (3-CF 3 -phenyl)methyl-, (3-CH 3 O-phenyl)methyl-, (3-CF 3 O-phenyl)methyl-, (2-F-phenyl)methyl-, (2-Cl-phenyl)methyl-, (2-CH 3 -phenyl)methyl-, (2-CF 3 -phenyl)methyl-, (2-CH 3 O-phenyl)methyl-, (2-CF 3 O-phenyl)methyl-, 2-pyridyl-, 3-pyridyl-, 4-pyridyl-, 1-piperidinyl, 1-homopiperidinyl, and 1-morpholino; and
R 13 , at each occurrence, is independently selected from H, F, Cl, and methoxy.
10 . A compound, according to claim 1 , of Formula (Ic);
or a pharmaceutically acceptable salt form or prodrug thereof.
11 . A compound, according to claim 1 , of Formula (Id);
or a pharmaceutically acceptable salt form or prodrug thereof.
12 . A compound, according to claim 1 , of Formula (Ia):
or a pharmaceutically acceptable salt or prodrug thereof.
13 . A compound of claim 1 wherein R 5 is OR 14 .
14 . A compound of claim 1 wherein R 5 is C 1 -C 4 alkoxy substituted with 0-3 R 5b .
15 . A compound selected from:
2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-propionamide; 2-(3-bromo-5-chloro-thiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(naphthalene-1-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(5-dimethylamino naphthalene-1-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(naphthalene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2-acetamido-4-methylthiazole-5-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(thiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(quinoline-8-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2,5-dichlorophenyl sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(mesitylene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3-nitrophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-bromophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-fluorophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-chlorophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-acetamidophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-nitrophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-methoxyphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-tert-butylphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(p-toluene-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(benzyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(beta-styrene-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-((2-methoxycarbonyl)phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2-nitro-4-(trifluoromethyl)phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3-(trifluoromethyl)phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2,5-dimethoxyphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2-methylphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3,4-dichlorophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-(trifluoromethoxy)phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3,4-dimethoxyphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2-bromophenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3,5-bis(trifluoromethyl)phenyl-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-ethylphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-isopropylphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2,5-dichlorothiophene-3-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(5-chlorothiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2-(trifluoromethyl)phenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3-methylphenyl-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(2,3-dichlorothiophene-5-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-bromo-5-chlorothiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(5-[(benzoylamino)methyl]-thiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(4-phenylsulfonylthiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(5-(phenylsulfonyl)thiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-[2-(1-methyl-(5-trifluoromethyl)pyrazole)thiophene-5-sulfonylamino]-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(5-(2-pyridyl)thiophene-2-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-4-methyl-pentanoic acid [5-(4-fluoro-phenyl)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-amide; N-[1-(3′-Chloro-4′-fluoro-biphenyl-3-ylmethyl)-2-oxo-azepan-3-yl]-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-propionamide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-N-[5-(4-fluoro-phenyl)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-propionamide; 2-(2-fluoro-benzenesulfonylamino)-N-[5-(4-fluoro-phenyl)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-propionamide; N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2-(2-trifluoromethyl-benzenesulfonylamino)-propionamide; 2-(2-fluoro-benzenesulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 4-methyl-2-(2-trifluoromethyl-benzenesulfonylamino)-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 4-methyl-2-(propane-1-sulfonylamino)-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 4-methyl-2-(propane-1-sulfonylamino)-pentanoic acid (1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-N-[1-methyl-2-oxo-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-propionamide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-4-methyl-pentanoic acid (7-chloro-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 4-methyl-2-(propane-1-sulfonylamino)-pentanoic acid [5-(4-chloro-phenyl)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-amide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-4-methyl-pentanoic acid (1-methyl-2-oxo-5-pyridin-2-yl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide; 2-[(3,5-dimethyl-isoxazole-4-sulfonyl)-methyl-amino]-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-propionamide; 3-dimethylamino-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-propionamide; N-[1-methyl-2-oxo-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-2-(propane-1-sulfonylamino)-propionamide; N-(7-chloro-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-propionamide; 2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-4-methyl-pentanoic acid [5-(4-chloro-phenyl)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-amide; and 2-methanesulfonylamino-N-[1-methyl-2-oxo-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-propionamide.
16 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
17 . A method for the treatment of neurological disorders comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1 .
18 . A method for the treatment of neurological disorders associated with Aβ amyloid production comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1 .
19 . 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 .
20 . A method for the treatment of Alzheimer's Disease associated with Aβ amyloid production comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1 .
21 . A method for inhibiting γ-secretase activity comprising administering to a host in need of such inhibition a therapeutically effective amount of a compound of claim 1 that inhibits γ-secretase activity.Join the waitlist — get patent alerts
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