US2009111793A1PendingUtilityA1
Hydroxyalkanoylaminolactams and related structures as inhibitors of a beta protein production
Assignee: BRISTOL MYERS SQUIBB PHARMA COPriority: Sep 13, 1999Filed: Sep 9, 2008Published: Apr 30, 2009
Est. expirySep 13, 2019(expired)· nominal 20-yr term from priority
A61P 25/28C07D 223/10C07D 223/12A61P 25/00C07D 243/08C07D 243/24C07D 223/16C07D 243/26C07D 243/14C07D 401/04C07D 223/18
66
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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-modified1 . A process for preparing a compound of formula (I)
or a stereoisomer or pharmaceutically acceptable salt forms thereof,
wherein B is
the process comprising a scheme illustrated in synthetic steps (1),
wherein a carboxylic acid 4a can be coupled to an
appropriate dibenzo azepinone lactam intermediate as illustrated in scheme 2a,
wherein:
wherein according to Formula (I)
Q is Q 1 ,
—(C 1 -C 3 alkylene)-O-Q 1 ,
—(C 1 -C 3 alkylene)-S-Q 1 ,
—(C 1 -C 3 alkylene)-S(═O)-Q 1 ,
—(C 1 -C 3 alkylene)-S(═O) 2 -Q 1 , or
—(C 1 -C 3 alkylene)-N(R 20 )-Q 1 ;
Q 1 is C 1 -C 8 alkyl substituted with 0-3 R 1a ;
C 2 -C 8 alkenyl substituted with 0-3 R 1a ;
C 2 -C 8 alkynyl 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 ;
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, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, NR 15 R 16 , CF 3 ;
C 3 -C 10 carbocycle substituted with 0-3 R 1b ;
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, 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, C 1 -C 4 haloalkyl-S—, and (C 1 -C 6 alkyl)-O—C(═O)—;
R 2 is H, methyl, ethyl, propyl, or butyl;
R 3 is H;
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 ;
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 0-3R 5c ;
R 5a is H, C 1 -C 4 alkyl, or C 2 -C 4 alkenyl;
alternatively, R 5 and R 5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R 5c ; optionally the cycloalkyl ring formed by combining R 5 and R 5a may be benzo fused, wherein the benzo fused ring may be substituted with 0-3 R 5c ;
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, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, 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 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 10 carbocycle substituted with 0-3 R 5c ;
aryl 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, 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 or C 1 -C 6 alkyl;
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 9 cycloalkyl;
X is a bond;
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 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, 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 9 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 —, —C(═O)O—, or —OC(═O)—;
Z is H;
C 1 -C 8 alkyl substituted with 0-2 R 12 ;
C 2 -C 4 alkenyl substituted with 0-2 R 12 ;
C 2 -C 4 alkynyl substituted with 0-2 R 12 ;
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 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, and 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 H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 6 alkyl, and C 2 -C 6 alkoxyalkyl;
R 14a is H, phenyl, benzyl, or C 1 -C 6 alkyl;
R 15 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—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, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—C(═O)— and (C 1 -C 6 alkyl)-S(═O) 2 —;
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, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl,
aryl substituted by 0-4 R 17a , or
aryl-CH 2 — wherein said aryl is 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 , S(═O) 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 —;
alternatively, —NR 18 R 19 may be a heterocyclic ring selected from the group: piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; wherein said heterocyclic ring is substituted with 0-3 R 11b —;
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 selected from H and C 1 -C 6 alkyl;
R 20 is H, OH, C 1 -C 4 alkyl, phenyl, benzyl, or phenethyl;
R 21 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, and phenethyl; and
R 22 , at each occurrence, is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, and phenethyl.
2 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt forms thereof,
Q is Q 1 ,
(C 1 -C 3 alkyl) O-Q 1 ,
(C 1 -C 3 alkyl)-S-Q 1 ,
(C 1 -C 3 alkyl)-S(═O)-Q 1 ,
(C 1 -C 3 alkyl)-S(═O) 2 -Q 1 , or
(C 1 -C 3 alkyl)-N(R 20 )-Q 1 ;
Q 1 is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 2 -C 6 alkenyl substituted with 0-3 R 1a ;
C 2 -C 6 alkynyl 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,
C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, NR 15 R 16 , CF 3 ;
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, 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, C 1 -C 4 haloalkyl-S—, and (C 1 -C 6 alkyl)-O—C(═O)—;
R 2 is H, methyl, or ethyl;
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 0-3R 5c ;
R 5a is H, C 1 -C 4 alkyl, or C 2 -C 4 alkenyl;
alternatively, R 5 and R 5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R 5c ;
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, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—,
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—;
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 3 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, halo;
C 1 -C 4 alkyl substituted with 0-2 R 12 ;
C 2 -C 4 alkenyl substituted with 0-2 R 12 ;
C 2 -C 4 alkynyl substituted with 0-2 R 12 ;
C 6 -C 10 aryl substituted with 0-4 R 12b ;
C 3 -C 6 carbocycle substituted with 0-4 R 12b ; 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 0-3 R 12b ;
Ring B is:
R 12 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, and C 1 -C 4 haloalkyl-S—;
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 , 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 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—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, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—C(═O)— and (C 1 -C 6 alkyl)-S(═O) 2 —;
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 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 —;
alternatively, —NR 18 R 19 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; and
R 20 is H, OH, C 1 -C 4 alkyl, phenyl, benzyl, or phenethyl.
3 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Ring B is:
Q is Q 1 or (C 1 -C 3 alkyl)-O-Q 1 ;
Q 1 is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 2 -C 6 alkenyl substituted with 0-3 R 1a ;
C 2 -C 6 alkynyl 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,
C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, NR 15 R 16 , CF 3 ;
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, 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, C 1 -C 4 haloalkyl-S—, and (C 1 -C 6 alkyl)-O—C(═O)—;
R 2 is H, methyl, or ethyl;
R 5 is H, OR 14 ;
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 6 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 6 carbocycle 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 ;
R 5a is H, C 1 -C 4 alkyl, or C 2 -C 4 alkenyl;
alternatively, R 5 and R 5a may be combined to form a C 4 -C 7 cycloalkyl ring;
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, SCH 3 , S(═O)CH 3 , S(═O) 2 CH 3 , C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—,
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—;
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, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 R Xb ;
C 3 -C 6 cycloakyl 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 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, F, Cl, Br;
C 1 -C 4 alkyl substituted with 0-2 R 12 ;
C 2 -C 4 alkenyl substituted with 0-2 R 12 ;
C 2 -C 4 alkynyl substituted with 0-2 R 12 ;
C 6 -C 10 aryl substituted with 0-4 R 12b ;
C 3 -C 6 carbocycle substituted with 0-4 R 12b ; 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 0-3 R 12b ;
R 12 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, and C 1 -C 4 haloalkyl-S—;
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 , 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 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—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, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-O—C(═O)— and (C 1 -C 6 alkyl)-S(═O) 2 —;
alternatively, —NR 15 R 16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; and
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 1 -C 6 alkyl)-C(═O)— and (C 1 -C 6 alkyl)-S(═O) 2 —;
alternatively, —NR 18 R 19 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; and
R 19 , at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl.
4 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Ring B is:
Q is Q 1 ;
Q 1 is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 2 -C 6 alkenyl substituted with 0-3 R 1a ;
C 2 -C 6 alkynyl 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,
C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, NR 15 R 16 , CF 3 ;
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, 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, C 1 -C 4 haloalkyl-S—, and (C 1 -C 6 alkyl)-O—C(═O)—;
R 2 is H, methyl, or ethyl;
R 5 is H, OR 14 ;
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 5a is H, methyl, ethyl, propyl, butyl, or C 2 -C 4 alkenyl;
alternatively, R 5 and R 5a may be combined to form a C 4 -C 7 cycloalkyl ring;
R 5b , at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF 3 , OR 14 , Cl, F, Br, I, ═O, NR 15 R 16 ,
C 3 -C 7 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 7 carbocycle 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, 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;
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 5 -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 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, —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 —, or —N(R 19 )—;
Z is H, F, Cl, Br,
C 1 -C 4 alkyl substituted with 0-2 R 12 ;
C 2 -C 4 alkenyl substituted with 0-2 R 12 ;
C 2 -C 4 alkynyl substituted with 0-2 R 12 ;
C 6 -C 10 aryl substituted with 0-4 R 12b ;
C 1 -C 6 carbocycle substituted with 0-4 R 12b ; 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 0-3 R 12b ;
R 12 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, and C 1 -C 4 haloalkyl-S—;
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 , and CF 3 ;
R 14 , at each occurrence, is independently selected from H, phenyl, benzyl, C 1 -C 4 alkyl, and 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 C(═O)—, CH 3 OC(═O)—, CH 3 CH 2 S(═O) 2 — and CH 3 S(═O) 2 —;
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, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and
R 19 , at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, and butyl.
5 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Ring B is:
Q is Q 1 ,
Q 1 is C 1 -C 6 alkyl substituted with 0-3 R 1a ;
C 2 -C 6 alkenyl substituted with 0-3 R 1a ;
C 2 -C 6 alkynyl substituted with 0-3 R 1a ;
C 3 -C 6 cycloalkyl substituted with 0-3 R 1b ;
phenyl substituted with 0-3 R 1b ; 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 0-3 R 1b ;
R 1a , at each occurrence, is independently selected from
H, methyl, ethyl, propyl, butyl, OR 14 , Cl, F, Br, I, NR 15 R 16 , CF 3 ;
C 3 -C 6 carbocycle substituted with 0-3 R 1b ;
phenyl substituted with 0-3 R 1b ; 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 1b ;
R 1b , 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 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, (methyl)OC(═O)—, (ethyl)OC(═O)—, (propyl)OC(═O)—, and (butyl)OC(═O)—;
R 2 is H or methyl;
R 5 is H, OR 14 ;
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 5a is H, methyl, ethyl, propyl, or butyl;
alternatively, R 5 and R 5a may be combined to form a cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl ring;
R 5b , at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF 3 , OR 14 , Cl, F, ═O, NR 15 R 16 ,
C 3 -C 7 cycloalkyl substituted with 0-3 R 5c ;
C 3 -C 7 carbocycle 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 ; 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)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 a bond, —CH 2 —, or —CH(CH 3 )—;
X is a bond;
phenyl substituted with 0-1 R Xb ;
C 5 -C 6 cycloalkyl substituted with 0-1 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 substituted with 0-1 R Xb ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, and isoxazolyl;
R Xb , at each occurrence, is independently selected from H, OH, Cl, F, Br, 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;
Y is a bond, —V—, —V—CH 2 —, or —CH 2 V—;
V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O) 2 —, or —N(R 19 )—;
Z is H, F, Cl, Br,
C 1 -C 4 alkyl substituted with 0-2 R 12 ;
C 2 -C 4 alkenyl substituted with 0-2 R 12 ;
C 2 -C 4 alkynyl substituted with 0-2 R 12 ;
C 6 -C 10 aryl substituted with 0-4 R 12b ;
C 3 -C 6 carbocycle substituted with 0-4 R 12b ; 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 0-3 R 12b ;
R 12 at each occurrence, is independently selected from H, OH, Cl, F, Br, NR 15 R 16 , —C(═O)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;
phenyl substituted with 0-4 R 12b ;
C 3 -C 6 carbocycle substituted with 0-4 R 12b ; 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 0-3 R 12b ;
R 12b , at each occurrence, is independently selected from H, OH, Cl, F, Br, 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 H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR 15 R 16 , 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;
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, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and, phenethyl.
6 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Ring B is:
Q is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 ,
—CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 ,
—CH═CH 2 , —CH 2 CH═CH 2 , —CH 2 C(CH 3 )═CH 2 , —CH 2 CH═C(CH 3 ) 2 , —CH 2 CH 2 CH═CH 2 , —CH 2 CH 2 C(CH 3 )═CH 2 , —CH 2 CH 2 CH═C(CH 3 ) 2 , cis-CH 2 CH═CH(CH 3 ), cis-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(CH 3 ), trans-CH 2 CH 2 CH═CH(CH 3 );
—C≡CH, —CH 2 C≡CH, —CH 2 C≡C(CH 3 ),
cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclopropyl-CH 2 —, cyclobutyl-CH 2 —, cyclopentyl-CH 2 —, cyclohexyl-CH 2 —, cyclopropyl-CH 2 CH 2 —, cyclobutyl-CH 2 CH 2 —, cyclopentyl-CH 2 CH 2 —, cyclohexyl-CH 2 CH 2 —,
phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-, 4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-, 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-furanyl-CH 2 —, 3-furanyl-CH 2 —, 2-thienyl-CH 2 —, 3-thienyl-CH 2 —, 2-pyridyl-CH 2 —, 3-pyridyl-CH 2 —, 4-pyridyl-CH 2 —, 1-imidazolyl-CH 2 —, 2-oxazolyl-CH 2 —, 4-oxazolyl-CH 2 —, 5-oxazolyl-CH 2 —, 3-isoxazolyl-CH 2 —, 4-isoxazolyl-CH 2 —, 5-isoxazolyl-CH 2 —,
phenyl-CH 2 CH 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 —;
furanyl-CH 2 CH 2 —, thienyl-CH 2 CH 2 —, pyridyl-CH 2 CH 2 —, 1-imidazolyl-CH 2 CH 2 —, oxazolyl-CH 2 CH 2 —, isoxazolyl-CH 2 CH 2 —, 3,5-dimethylisoxazol-4-yl-CH 2 CH 2 —, phenyl-propyl-;
benzyl-CH(NH 2 )—, benzyl-CH(NHC(═O)—O-tBu)-, benzyloxy-CH 2 —, pyrrolidin-2-yl-, or 3-t-butoxycarbonylpyrrolidin-2-yl-;
R 2 is H or methyl;
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 1 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 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 ,
—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 ,
—CH═CH 2 , —CH 2 CH═CH 2 , —CH 2 CH 2 CH═CH 2 , —CH═CHCH 3 , cis-CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(C 6 H 5 ), —CH 2 CH═C(CH 3 ) 2 , cis-CH 2 CH═CHCH 2 CH 3 , trans-CH 2 CH═CHCH 2 CH 3 , cis-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CHCH 2 (C 6 H 5 ),
—C≡CH, —CH 2 C≡CH, —CH 2 C≡C(CH 3 ), —CH 2 C≡C(C 6 H 5 ), —CH 2 CH 2 C≡CH, —CH 2 CH 2 C≡C(CH 3 ), —CH 2 CH 2 C≡C(C 6 H 5 ), —CH 2 CH 2 CH 2 C≡CH, —CH 2 CH 2 CH 2 C≡C(CH 3 ), —CH 2 CH 2 CH 2 C≡C(C 6 H 5 ),
cyclopropyl-CH 2 —, cyclobutyl-CH 2 —, cyclopentyl-CH 2 —, cyclohexyl-CH 2 —, (2-CH 3 -cyclopropyl)CH 2 —, (3-CH 3 -cyclobutyl)CH 2 —, cyclopropyl-CH 2 CH 2 —, cyclobutyl-CH 2 CH 2 —, cyclopentyl-CH 2 CH 2 —, cyclohexyl-CH 2 CH 2 —, (2-CH 3 -cyclopropyl)CH 2 CH 2 —, (3-CH 3 -cyclobutyl)CH 2 CH 2 —,
phenyl-CH 2 —, (2-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 —, (3,5-diF-phenyl)CH 2 —, 2-furanyl-CH 2 —, 3-furanyl-CH 2 —, 2-thienyl-CH 2 —, 3-thienyl-CH 2 —, 2-pyridyl-CH 2 —, 3-pyridyl-CH 2 —, 4-pyridyl-CH 2 —, 1-imidazolyl-CH 2 —, 2-oxazolyl-CH 2 —, 4-oxazolyl-CH 2 —, 5-oxazolyl-CH 2 —, 3-isoxazolyl-CH 2 —, 4-isoxazolyl-CH 2 —, 5-isoxazolyl-CH 2 —,
phenyl-CH 2 CH 2 —, (2-F-phenyl)CH 2 CH 2 —, (3-F-phenyl)CH 2 CH 2 —, (4-F-phenyl)CH 2 CH 2 —, furanyl-CH 2 CH 2 —, thienyl-CH 2 CH 2 —, pyridyl-CH 2 CH 2 —, 1-imidazolyl-CH 2 CH 2 —, oxazolyl-CH 2 CH 2 —, isoxazolyl-CH 2 CH 2 —;
methoxy, ethoxy, propoxy, or butoxy;
R 5a is H;
alternatively, R 5 and R 5a may be combined to form cyclopentyl, cyclohexyl, or cycloheptyl;
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—, or —N(CH 3 )—;
Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
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-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-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-PhO-phenyl)CH 2 —, (3-PhO-phenyl)CH 2 —, (4-PhO-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-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 13 , at each occurrence, is independently selected from H, MeO, F, and Cl.
7 . The process according to claim 1 , for producing a compound of Formula (Ia)
or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Ring B is:
or a stereoisomer or pharmaceutically acceptable salt forms thereof,
wherein:
Q is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 ,
—CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 ,
—CH═CH 2 , —CH 2 CH═CH 2 , —CH 2 C(CH 3 )═CH 2 , —CH 2 CH═C(CH 3 ) 2 , —CH 2 CH 2 CH═CH 2 , —CH 2 CH 2 C(CH 3 )═CH 2 , —CH 2 CH 2 CH═C(CH 3 ) 2 , cis-CH 2 CH═CH(CH 3 ), cis-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(CH 3 ), trans-CH 2 CH 2 CH═CH(CH 3 );
—C≡CH, —CH 2 C≡CH, —CH 2 C≡C(CH 3 ),
cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclopropyl-CH 2 —, cyclobutyl-CH 2 —, cyclopentyl-CH 2 —, cyclohexyl-CH 2 —, cyclopropyl-CH 2 CH 2 —, cyclobutyl-CH 2 CH 2 —, cyclopentyl-CH 2 CH 2 —, cyclohexyl-CH 2 CH 2 —,
phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-, 4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-, 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-furanyl-CH 2 —, 3-furanyl-CH 2 —, 2-thienyl-CH 2 —, 3-thienyl-CH 2 —, 2-pyridyl-CH 2 —, 3-pyridyl-CH 2 —, 4-pyridyl-CH 2 —, 1-imidazolyl-CH 2 —, 2-oxazolyl-CH 2 —, 4-oxazolyl-CH 2 —, 5-oxazolyl-CH 2 —, 3-isoxazolyl-CH 2 —, 4-isoxazolyl-CH 2 —, 5-isoxazolyl-CH 2 —,
phenyl-CH 2 CH 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 —;
furanyl-CH 2 CH 2 —, thienyl-CH 2 CH 2 —, pyridyl-CH 2 CH 2 —, 1-imidazolyl-CH 2 CH 2 —, oxazolyl-CH 2 CH 2 —, isoxazolyl-CH 2 CH 2 —, 3,5-dimethylisoxazol-4-yl-CH 2 CH 2 —, phenyl-propyl-;
benzyl-CH(NH 2 )—, benzyl-CH(NHC(═O)—O-tBu)-, benzyloxy-CH 2 —, pyrrolidin-2-yl-, or 3-t-butoxycarbonylpyrrolidin-2-yl-;
R 2 is H or methyl;
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 ,
—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 ,
—CH═CH 2 , —CH 2 CH═CH 2 , —CH 2 CH 2 CH═CH 2 , —CH═CHCH 3 , cis-CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CH(C 6 H 5 ), —CH 2 CH═C(CH 3 ) 2 , cis-CH 2 CH═CHCH 2 CH 3 , trans-CH 2 CH═CHCH 2 CH 3 , cis-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH 2 CH═CH(CH 3 ), trans-CH 2 CH═CHCH 2 (C 6 H 5 ),
—C≡CH, —CH 2 C≡CH, —CH 2 C≡C(CH 3 ), —CH 2 C≡C(C 6 H 5 ), —CH 2 CH 2 C≡CH, —CH 2 CH 2 C≡C(CH 3 ), —CH 2 CH 2 C≡C(C 6 H 5 ), —CH 2 CH 2 CH 2 C≡CH, —CH 2 CH 2 CH 2 C≡C(CH 3 ), —CH 2 CH 2 CH 2 C≡C(C 6 H 5 ),
cyclopropyl-CH 2 —, cyclobutyl-CH 2 —, cyclopentyl-CH 2 —, cyclohexyl-CH 2 —, (2-CH 3 -cyclopropyl)CH 2 —, (3-CH 3 -cyclobutyl)CH 2 —, cyclopropyl-CH 2 CH 2 —, cyclobutyl-CH 2 CH 2 —, cyclopentyl-CH 2 CH 2 —, cyclohexyl-CH 2 CH 2 —, (2-CH 3 -cyclopropyl)CH 2 CH 2 —, (3-CH 3 -cyclobutyl)CH 2 CH 2 —,
phenyl-CH 2 —, (2-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 —, (3,5-diF-phenyl)CH 2 —, 2-furanyl-CH 2 —, 3-furanyl-CH 2 —, 2-thienyl-CH 2 —, 3-thienyl-CH 2 —, 2-pyridyl-CH 2 —, 3-pyridyl-CH 2 —, 4-pyridyl-CH 2 —, 1-imidazolyl-CH 2 —, 2-oxazolyl-CH 2 —, 4-oxazolyl-CH 2 —, 5-oxazolyl-CH 2 —, 3-isoxazolyl-CH 2 —, 4-isoxazolyl-CH 2 —, 5-isoxazolyl-CH 2 —,
phenyl-CH 2 CH 2 —, (2-F-phenyl)CH 2 CH 2 —, (3-F-phenyl)CH 2 CH 2 —, (4-F-phenyl)CH 2 CH 2 —, furanyl-CH 2 CH 2 —, thienyl-CH 2 CH 2 —, pyridyl-CH 2 CH 2 —, 1-imidazolyl-CH 2 CH 2 —, oxazolyl-CH 2 CH 2 —, isoxazolyl-CH 2 CH 2 —;
methoxy, ethoxy, propoxy, or butoxy;
R 5a is H;
alternatively, R 5 and R 5a may be combined to form cyclopentyl, cyclohexyl, or cycloheptyl;
W is a bond;
X is a bond;
Y is a bond;
Z is H, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
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, N-oxide-pyridinyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, 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-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-PhO-phenyl)CH 2 —, (3-PhO-phenyl)CH 2 —, (4-PhO-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-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, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 2-F-phenyl-, 3-F-phenyl, 4-F-phenyl, 4-Cl-phenyl, 4-CH 3 -phenyl, 4-MeO-phenyl-, 4-CF 3 -phenyl, (4-F-phenyl)CH 2 —, (4-Cl-phenyl)CH 2 —, (4-CH 3 -phenyl)CH 2 —, (4-CF 3 -phenyl)CH 2 —, (4-F-phenyl)CH 2 CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, (4-CH 3 -phenyl)CH 2 CH 2 —, (4-CF 3 -phenyl)CH 2 CH 2 —, pyridin-2-yl-, pyridin-3-yl-, 4-CF 3 -pyridin-2-yl-, 4-CH 3 -pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, and N,N-dibutylamino; and
R 13 , at each occurrence, is independently selected from H, MeO, F, and Cl.
8 . A process according to claim 1 , for preparing a compound of formula (Ie)
or a stereoisomer or a pharmaceutically acceptable salt form thereof, wherein
Q is n-butyl, n-pentyl, n-hexyl, 2-(furan-2-yl)-ethyl, and Z-Y—X—W— is methyl, Q is n-butyl when Z-Y—X—W is 2-diethylaminoethyl, 3-hydroxypropyl, n-butyl or benzyl.
9 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 1 and a pharmaceutically acceptable carrier.
10 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 2 and a pharmaceutically acceptable carrier.
11 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 3 and a pharmaceutically acceptable carrier.
12 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 4 and a pharmaceutically acceptable carrier.
13 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 5 and a pharmaceutically acceptable carrier.
14 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 6 and a pharmaceutically acceptable carrier.
15 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 7 and a pharmaceutically acceptable carrier.
16 . A method for preparing a pharmaceutical composition comprising combining a compound prepared according to the process of claim 8 and a pharmaceutically acceptable carrier.Join the waitlist — get patent alerts
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