USRE39680EExpiredUtilityPatentIndex 97
Substituted heterocycle fused gamma-carbolines
Assignee: BRISTOL MYERS SQUIBB PHARMA COPriority: Jun 15, 1999Filed: Feb 16, 2006Granted: Jun 5, 2007
Est. expiryJun 15, 2019(expired)· nominal 20-yr term from priority
Inventors:ROBICHAUD ALBERT JLEE TAEKYUDENG WEIMITCHELL IAN SYANG MICHAEL GUANGHAYDAR SIMONCHEN WENTINGMCCLUNG CHRISTOPHER DCALVELLO EMILE J BZAWROTNY DAVID MRAJAGOPALAN PARTHASARATHL
A61P 43/00A61P 3/04A61P 25/00A61P 25/18A61P 25/24A61P 25/06A61P 25/22A61P 25/20C07D 491/06A61P 15/00C07D 471/06A61P 1/00C07D 223/32C07D 495/06C07D 221/18
97
PatentIndex Score
142
Cited by
42
References
21
Claims
Abstract
The present invention is directed to certain novel compounds represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R 1 , R 5 , R 6a , R 6b , R 7 , R 8 , R 9 , X, b, k, m, and n, and the dashed lines are described herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain disorders. The compounds of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including obesity, anxiety, depression, psychosis, schizophrenia, sleep disorders, sexual disorders, migraine, conditions associated with cephalic pain, social phobias, and gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility.
Claims
exact text as granted — not AI-modified1. A compound of the formula (I)
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein:
b is a single bond;
X is —NR 10A —;
R 1 is selected from
H,
C(═O)R 2 ,
C(═O)OR 2 ,
C 1-8 alkyl,
C 2-8 alkenyl,
C 2-8 alkynyl,
C 3-7 cycloalkyl,
C 1-6 alkyl substituted with Z,
C 2-6 alkenyl substituted with Z,
C 2-6 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-3 alkyl substituted with Y,
C 2-3 alkenyl substituted with Y,
C 2-3 alkynyl substituted with Y,
C 1-6 alkyl substituted with 0-2 R 2 ,
C 2-6 alkenyl substituted with 0-2 R 2 ,
C 2-6 alkynyl substituted with 0-2 R 2 ,
aryl substituted with 0-2 R 2 , and
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0-2 R 2 ;
Y is selected from
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 3-6 cycloalkyl substituted with —(C 1-3 alkyl)-Z,
aryl substituted with —(C 1-3 alkyl)-Z, and
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with —(C 1-3 alkyl)-Z;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—OC(O) R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from halo,
C 1-3 haloalkyl,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0-5 R 42 ;
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 3 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 5 is H or C 1-4 alkyl;
R 6a and R 6b , at each occurrence, are independently selected from
H, —OH, —NR 46 R 47 , —CF 3 , C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, and
aryl substituted with 0-3 R 44 ;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 2-4 alkenyl substituted with 0-2 R 11 ,
C 2-4 alkynyl substituted with 0-1 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10A is selected from H,
C 1-6 alkyl substituted with 0-1 R 10B ,
C 2-6 alkenyl substituted with 0-1 R 10B ,
C 2-6 alkynyl substituted with 0-1 R 10 , and
C 16 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
phenyl substituted with 0-3 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0-1 R 12a ,
C 2-4 alkenyl substituted with 0-1 R 12a ,
C 2-4 alkynyl substituted with 0-1 R 12a ,
C 3-6 cycloalkyl substituted with 0-3 R 33 ,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0-3 R 16 ;
R 14 , at each occurrence, is independently selected from H 12 and C 1-4 alkyl;
R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl,
C 1-3 haloalkyl-oxy-, and C 1-3 alkyloxy-;
R 31 , at each occurrence, is independently selected from H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-,
C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—,
C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, —CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O;
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SOR 45 , SR 45 , NR 46 SO 2 R 45 , NR 46 COR 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from
H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 ,
C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from
H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from
H,
C 1-4 alkyl, —C(═O)NH(C 1-4 alkyl), —SO 2 (C 1-4 alkyl),
—C(═O)O(C 1-4 alkyl), —C(═O) (C 1-4 alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, or 2; and
n is 1, 2, or 3;
provided when m is 0 or 1 then k is 1 or 2;
provided when m is 2 then k is 1.
2. A compound of claim 1 wherein:
X is —NR 10A ;
R 1 is selected from
H,
C(═O)R 2 ,
C(═O)OR 2 ,
C 1-8 alkyl,
C 2-8 alkenyl,
C 2-8 alkynyl,
C 3-7 cycloalkyl,
C 1-6 alkyl substituted with 0-2 R 2 ,
C 2-6 alkenyl substituted with 0-2 R 2 ,
C 2-6 alkynyl substituted with 0-2 R 2 , aryl substituted with 0-2 R 2 , and
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0-2 R 2 ;
R 2 , at each occurrence, is independently selected from
F, Cl, CH 2 F, CHF 2 , CF 3 ,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 42 ;
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and
aryl substituted with 0-3 R 44 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 S(O)NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 2-4 alkenyl substituted with 0-2 R 11 ,
C 2-4 alkynyl substituted with 0-1 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10A is selected from H,
C 1-6 alkyl substituted with 0-1 R 10B ,
C 2-6 alkenyl substituted with 0-1 R 10B ,
C 2-6 alkynyl substituted with 0-1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
phenyl substituted with 0-3 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0-1 R 12a ,
C 2-4 alkenyl substituted with 0-1 R 12a ,
C 2-4 alkynyl substituted with 0-1 R 12a ,
C 3-6 cycloalkyl substituted with 0-3 R 33 ,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0-3 R 16 ;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl,
C 1-3 haloalkyl-oxy-, and C 1-3 alkyloxy-;
R 31 , at each occurrence, is independently selected from H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-,
C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—,
C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, —CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN;
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 ,
—OCF 3 , —CN, —NO 2 , C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H, and C 1-4 alkyl;
k is 1 or 2;
m is 0, 1, or 2; and
n is 1, 2, or 3.
3. A compound of claim 2 wherein:
X is —NR 10A ;
R 1 is selected from
H,
C(═O)R 2 ,
C(═O)OR 2 ,
C 1-6 alkyl,
C 2-6 alkenyl,
C 2-6 alkynyl,
C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-2 R 2 ,
C 2-4 alkenyl substituted with 0-2 R 2 , and
C 2-4 alkynyl substituted with 0-2 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 42 ;
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected independently from
H, —OH, —NR 46 R 47 , —CF 3 , C 1-3 alkyl, and C 1-3 alkoxy;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 16 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , and NR 14 S(O) 2 R 12 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 2-4 alkenyl substituted with 0-2 R 11 ,
C 2-4 alkynyl substituted with 0-1 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10A is selected from H,
C 1-4 alkyl substituted with 0-1 R 10B ,
C 2-4 alkenyl substituted with 0-1 R 10B ,
C 2-4 alkynyl substituted with 0-1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
phenyl substituted with 0-3 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 , C 1-6 alkyl,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O)NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0-1 R 12a ,
C 2-4 alkenyl substituted with 0-1 R 12a ,
C 2-4 alkynyl substituted with 0-1 R 12a ,
C 3-6 cycloalkyl substituted with 0-3 R 33 ,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12a , at each occurrence, is independently selected from
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S, wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0-3 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl and butyl;
R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
R 16 , at each occurrence, is independently selected from
H, OH, F, Cl, CN, NO 2 , CF 3 , SO 2 R 45 ; NR 46 R 47 , —C(═O)H,
methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and
trifluoromethoxy;
R 31 , at each occurrence, is independently selected from H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , and C 1-4 alkyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-,
C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—,
C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, —CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF3, —OCF 3 , —CN, —NO 2 ,
C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H, and C 1-4 alkyl;
k is 1 or 2;
m is 0 or 1; and
n is 1 or 2.
4. A compound of claim 2 wherein:
X is —NH—;
R 1 is selected from
H,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-4 cycloalkyl,
C 1-3 alkyl substituted with 0-1 R 2 ,
C 2-3 alkenyl substituted with 0-1 R 2 , and
C 2-3 alkynyl substituted with 0-1 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 42 ;
C 3-6 carbocyclic group substituted with 0-3 R 41 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is H, methyl, ethyl, methoxy, —OH, or —CF 3 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 , aryl substituted with 0-5 R 33 , and 5-6 membered heterocyclic ring system containing 1, 2 or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 8 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 2-4 alkenyl substituted with 0-2 R 11 ,
C 2-4 alkynyl substituted with 0-1 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 3- 10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0-1 R 12a ,
C 2-4 alkenyl substituted with 0-1 R 12a ,
C 2-4 alkynyl substituted with 0-1 R 12a ,
C 3-6 cycloalkyl substituted with 0-3 R 33 ,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12a , at each occurrence, is independently selected from phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of one N, two N, three N, one N one O, and one N one S; wherein said bicyclic heterocyclic ring system is unsaturated or partially saturated, wherein said bicyclic heterocyclic ring system is substituted with 0-2 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl and butyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 16 , at each occurrence, is independently selected from H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-,
C 1-4 alkyloxy-,
C 1-4 alkylthio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C(═O)NH—,
C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy,
propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, —CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, and C 1-3 alkyl;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 3-6 cycloalkyl, and C 1-3 alkyl;
R 43 is cycloalkyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 ,
methyl, ethyl, propyl, butyl, methoxy, ethoxy,
propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 1 or 2.
5. A compound of claim 2 wherein:
X is —NH—;
R 1 is selected from
H,
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-4 cycloalkyl,
C 1-3 alkyl substituted with 0-1 R 2 ,
C 2-3 alkenyl substituted with 0-1 R 2 , and
C 2-3 alkynyl substituted with 0-1 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 42 ;
C 3-6 carbocyclic group substituted with 0-3 R 41 ; and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is H, methyl, ethyl, methoxy, —OH, or —CF 3 ;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, F, C 1, -CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ,
R 8 is selected from
H, F, Cl, Br, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl,
C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 2-4 alkenyl substituted with 0-2 R 11 ,
C 2-4 alkynyl substituted with 0-1 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 ,
NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ; R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-4 haloalkyl)oxy,
C 3-10 cycloalkyl substituted with 0-2 R 33 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl substituted with 0-1 R 12a ,
C 2-4 alkenyl substituted with 0-1 R 12a ,
C 2-4 alkynyl substituted with 0-1 R 12a ,
C 3-6 cycloalkyl substituted with 0-3 R 33 ,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 12a , at each occurrence, is independently selected from phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S; wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl; wherein said bicyclic heterocyclic ring system is substituted with 0-1 R 16 ;
R 14 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 15 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 16 , at each occurrence, is independently selected from H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 31 , at each occurrence, is independently selected from H, OH, halo, CF 3 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 , —C(═O)H,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
C 3-6 cycloalkyl, C 1-4 haloalkyl, C 1-4 haloalkyl-oxy-,
C 1-4 alkyloxy-,
C 1-4 alkythio-, C 1-4 alkyl-C(═O)—, C 1-4 alkyl-C (═O)NH—,
C 1-4 alkyl-OC(═O)—,
C 1-4 alkyl-C(═O)O—, C 3-6 cycloalkyl-oxy-, C 3-6 cycloalkylmethyl-oxy-;
C 1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C 2-6 alkenyl substituted with OH, methoxy, ethoxy propoxy, or butoxy;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN,
C 2-4 alkenyl, C 2-4 alkynyl, C 13 alkoxy, C 1-3 haloalkyl, and C 1-3 alkyl;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 3-6 cycloalkyl, and C 1-3 alkyl;
R 43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 ,
methyl, ethyl, propyl, butyl, methoxy, ethoxy,
propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 1 or 2.
6. A compound of claim 2 wherein:
X is —NH—;
R 1 is selected from H,
C 1-5 alkyl substituted with 0-1 R 2 ,
C 2-5 alkenyl substituted with 0-1 R 2 , and
C 2-3 alkynyl substituted with 0-1 R 2 ;
R 2 is C 3-6 cycloalkyl;
R 5 is H, methyl, ethyl, or propyl;
R 6a is H, methyl, or ethyl;
R 6b is H;
R 7 and R 9 , at each occurrence, are independently selected from
H, F, Cl, —CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ,
R 8 is selected from
methyl substituted with R 11 ;
ethenyl substituted with R 11 ;
OR 12 e SR 12 , NR 12 R — 3, NR 12 C(O)R 15 , NR 12 C(O) OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 11 is selected from
phenyl-substituted with 0-5 fluoro;
2-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
2-(H 3 CC(═O))-phenyl-substituted with R 33 ;
2-(HC(═O))-phenyl-substituted with R 33 ;
2-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
2-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
2-(HOCH 2 )-phenyl-substituted with R 33 ;
2-(HOCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 CCH(OMe))-phenyl-substituted with R 33 ;
2-(H 3 COC(═O)-phenyl-substituted with R 33 ;
2-(HOCH 2 CH═CH)-phenyl-substituted with R 33 ;
2-((MeOC═O)CH═CH)-phenyl-substituted with R 33 ;
2-(methyl)-phenyl-substituted with R 33 ;
2-(ethyl)-phenyl-substituted with R 33 ;
2-(i-propyl)-phenyl-substituted with R 33 ;
2-(F 3 C)-phenyl-substituted with R 33 ;
2-(NC)-phenyl-substituted with R 33 ;
2-(H 3 CO)-phenyl-substituted with R 33 ;
2-(fluoro)-phenyl-substituted with R 33 ;
2-(chloro)-phenyl-substituted with R 33 ;
3-(NC)-phenyl-substituted with R 33 ;
3-(H 3 CO)-phenyl-substituted with R 33 ;
3-(fluoro)-phenyl-substituted with R 33 ;
3-(chloro)-phenyl-substituted with R 33 ;
4-(NC)-phenyl-substituted with R 33 ;
4-(fluoro)-phenyl-substituted with R 33 ;
4-(chloro)-phenyl-substituted with R 33 ;
4-(H 3 CS)-phenyl-substituted with R 33 ;
4-(H 3 CO)-phenyl-substituted with R 33 ;
4-(ethoxy)-phenyl-substituted with R 33 ;
4-(i-propoxy)-phenyl-substituted with R 33 ;
4-(i-butoxy)-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 C(═O))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
4-(H 3 CC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 CH(OH))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHCH (OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH((OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
4-(cyclopropyloxy)-phenyl substituted with R 33 ;
4-(cyclobutyloxy)-phenyl-substituted with R 33 ; and
4-(cyclopentyloxy)-phenyl-substituted with R 33 ;
R 12 is selected from
phenyl-substituted with 0-5 fluoro;
2-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
2-(H 3 CC(═O))-phenyl substituted with R 33 ;
2-(HC(═O))-phenyl substituted with R 33 ;
2-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
2-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
2-(HOCH 2 )-phenyl-substituted with R 33 ;
2-(HOCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 )-phenyl-substituted with R 33 ;
2-(H 3 COCH 2 CH 2 )-phenyl-substituted with R 33 ;
2-(H 3 CCH(OMe))-phenyl-substituted with R 33 ;
2-(H 3 COC(═O))-phenyl-substituted with R 33 ;
2-(HOCH 2 CH═CH)-phenyl-substituted with R 33 ;
2-((MeOC═O)CH═CH)-phenyl-substituted with R 33 ;
2-(methyl)-phenyl-substituted with R 33 ;
2-(ethyl)-phenyl-substituted with R 33 ;
2-(i-propyl)-phenyl-substituted with R 33 ;
2-(F 3 C)-phenyl-substituted with R 33 ;
2-(NC)-phenyl-substituted with R 33 ;
2-(H 3 CO)-phenyl-substituted with R 33 ;
2-(fluoro)-phenyl-substituted with R 33 ;
2-(chloro)-phenyl-substituted with R 33 ;
3-(NC)-phenyl-substituted with R 33 ;
3-(H 3 CO)-phenyl-substituted with R 33 ;
3-(fluoro)-phenyl-substituted with R 33 ;
3-(chloro)-phenyl-substituted with R 33 ;
4-(NC)-phenyl-substituted with R 33 ;
4-(fluoro)-phenyl-substituted with R 33 ;
4-(chloro)-phenyl-substituted with R 33 ;
4-(H 3 CS)-phenyl-substituted with R 33 ;
4-(H 3 CO)-phenyl-substituted with R 33 ;
4-(ethoxy)-phenyl-substituted with R 33 ;
4-(i-propoxy)-phenyl-substituted with R 33 ;
4-(i-butoxy)-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 C(═O))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 C(═O))-phenyl-substituted with R 33 ;
4-(H 3 CC(═O))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH 2 CH(OH))-phenyl-substituted with R 33 ;
4-((H 3 C) 2 CHCH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH 2 CH(OH))-phenyl-substituted with R 33 ;
4-(H 3 CCH(OH))-phenyl-substituted with R 33 ;
4-(cyclopropyloxy)-phenyl-substituted with R 33 ;
4-(cyclobutyloxy)-phenyl-substituted with R 33 ; and
4-(cyclopentyloxy)-phenyl-substituted with R 33 ;
R 13 is H, methyl, or ethyl;
alternatively, R 12 and R 13 join to form a 5- or 6- membered ring selected from pyrrolyl, pyrrolidinyl, imidazolyl, piperidinyl, piperizinyl, methylpiperizinyl, and morpholinyl;
alternatively, R 12 and R 13 when attached to N may be combined to form a 9- or 10-membered bicyclic heterocyclic ring system containing from 1-3 heteroatoms selected from the group consisting of N, O, and S; wherein said bicyclic heterocyclic ring system is selected from indolyl, indolinyl, indazolyl, benzimidazolyl, benzimidazolinyl, benztriazolyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, and dioxobenzthiazolyl; wherein said bicyclic heterocyclic ring system is substituted with 0-1 R 16 ;
R 15 is H, methyl, ethyl, propyl, or butyl;
R 16 , at each occurrence, is independently selected from H, OH, F, Cl, CN, NO 2 , methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R 33 , at each occurrence, is independently selected from H, F, Cl, —CH 3 , —OCH 3 , —CF 3 , —OCF 3 , —CN, and —NO 2 ;
k is 1;
m is 1; and
n is 1 or 2.
7. A compound of claim 2 of Formula (I-a)
wherein:
b is a single bond;
X is —NR 10A —;
R 1 is selected from
hydrogen, methyl, ethyl, n-propyl, n-butyl, s-butyl,
t-butyl, n-pentyl, n-hexyl, 2-propyl, 2-butyl, 2-pentyl,
2-hexyl, 2-methylpropyl, 2-methylbutyl, 2-methylpentyl,
2-ethylbutyl, 3-methylpentyl, 3-methylbutyl,
4-methylpentyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl,
2-propenyl, 2-methyl-2-propenyl, trans-2-butenyl,
3-methyl-butenyl, 3-butenyl, trans-2pentyl,
cis-2-pentenyl, 4-pentenyl, 4-methyl, 3-pentenyl,
3,3-dichloro-2-propenyl, trans-3-phenyl-2-propenyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl,
cyclohexylmethyl,
benzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl,
2,5-dimethylbenzyl, 2,4-dimethylbenzyl, 3,5-dimethylbenzyl,
2,4,6-trimethyl-benzyl, 3-methoxy-benzyl, 3,5-dimethoxy-benzyl, pentafluorobenzyl, 2-phenylethyl, 1-phenyl-2-propyl, 4-phenylbutyl, 4-phenylbenzyl, 2-phenylbenzyl,
(2,3-dimethoxy-phenyl)C(═O)—, (2,5-dimethoxy-phenyl)C(═O)—, (3,4-dimethoxy-phenyl)C(═O)—,
(3,5-dimethoxy-phenyl)C(═O)—, cyclopropyl-C(═O)—,
isopropyl-C(═O)—, ethyl-CO 2 —, propyl-CO 2 —, t-butyl-CO 2 —,
2,6-dimethoxy-benzyl, 2,4-dimethoxy-benzyl,
2,4,6-trimethoxy-benzyl, 2,3-dimethoxy-benzyl,
2,4,5-trimethoxy-benzyl, 2,3,4-trimethoxy-benzyl,
3,4-dimethoxy-benzyl, 3,4,5-trimethoxy-benzyl, (4-fluoro-phenyl)ethyl,
—CH═CH 2 , —CH 2 —CH═CH 2 , —CH═CH—CH 3 , —C≡—CH, —C≡C—CH 3 , and
—CH 2 —C≡—CH;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl,
propyl, isopropyl, butyl, t-butyl, nitro,
trifluoromethyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, phenyl,
methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—,
butylC(═O)—, phenylC(═O)—,
methylCO 2 -, ethylCO 2 -, propylCO 2 -, isopropylCO 2 -,
butylCO 2 -, phenylCO 2 -,
dimethylamino-S(═O)—, diethylamino-S(═O)—,
dipropylamino-S(═O)—, di-isopropylamino-S(═O)—,
dibutylamino-S(═O)—, diphenylamino-S(═O)—,
dimethylamino-SO 2 -, diethylamino-SO 2 -, dipropylamino-SO 2 -, di-isopropylamino-SO 2 -, dibutylamino-SO 2 -,
diphenylamino-SO 2 -,
dimethylamino-C(═O)—, diethylamino-C(═O)—,
dipropylamino-C(═O)—, di-isopropylamino-C(═O)—,
dibutylamino-C(═O)—, diphenylamino-C(═O)—,
2-chlorophenyl, 2-fluorophenyl, 2-bromophenyl, 2-cyanophenyl, 2-methylphenyl, 2-trifluoromethylphenyl,
2-methoxyphenyl, 2-trifluoromethoxyphenyl,
3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl,
3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl,
3-propylphenyl, 3-isopropylphenyl, 3-butylphenyl,
3-trifluoromethylphenyl, 3-methoxyphenyl,
3-isopropoxyphenyl, 3-trifluoromethoxyphenyl,
3-thiomethoxyphenyl,
4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl,
4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl,
4-propylphenyl, 4-isopropylphenyl, 4-butylphenyl,
4-trifluoromethylphenyl, 4-methoxyphenyl,
4-isopropoxyphenyl, 4-trifluoromethoxyphenyl,
4-thiomethoxyphenyl,
2,3-dichlorophenyl, 2,3-difluorophenyl, 2,3-dimethylphenyl,
2,3-ditrifluoromethylphenyl, 2,3-dimethoxyphenyl,
2,3-ditrifluoromethoxyphenyl,
2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dimethylphenyl,
2,4-ditrifluoromethylphenyl, 2,4-dimethoxyphenyl,
2,4-ditrifluoromethoxyphenyl,
2,5-dichlorophenyl, 2,5-difluorophenyl, 2,5-dimethylphenyl,
2,5-ditrifluoromethylphenyl, 2,5-dimethoxyphenyl,
2,5-ditrifluoromethoxyphenyl,
2,6-dichlorophenyl, 2,6-difluorophenyl, 2,6-dimethylphenyl,
2,6-ditrifluoromethylphenyl, 2,6-dimethoxyphenyl,
2,6-ditrifluoromethoxyphenyl,
3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl,
3,4-ditrifluoromethylphenyl, 3,4-dimethoxyphenyl,
3,4-ditrifluoromethoxyphenyl,
2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl,
2,4,6-trimethylphenyl, 2,4,6-trifluoromethylphenyl,
2,4,6-trimethoxyphenyl, 2,4,6-trifluoromethoxyphenyl,
2-chloro-4-CF 3 -phenyl, 2-fluoro-3-chloro-phenyl,
2-chloro-4-CF 3 -phenyl, 2-chloro-4-methoxy-phenyl,
2-methoxy-4-isopropyl-phenyl, 2-CF 3 -4-methoxy-phenyl,
2-methyl-4-methoxy-5-fluoro-phenyl,
2-methyl-4-methoxy-phenyl, 2-chloro-4-CF 3 O-phenyl,
2,4,5-trimethyl-phenyl, 2-methyl-4-chloro-phenyl,
methyl-C(═O)NH—, ethyl-C(═O)NH—, propyl-C(═O)NH—,
isopropyl-C(═O)NH—, butyl-C(═O)NH—, phenyl-C(═O)NH—,
4-acetylphenyl, 3-acetamidophenyl, 4-pyridyl, 2-furanyl,
2-thiophenyl, 2-naphthyl,
2-Me-5-F-phenyl, 2-F-5-Me-phenyl, 2-MeO-5-F-phenyl,
2-Me-3-Cl-phenyl, 3-NO 2 -phenyl, 2-NO 2 -phenyl,
2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl,
2-Cl-6-F-phenyl, 2-Cl-4-(CHF 2 )O-phenyl,
2,4-diMeO-6-F-phenyl, 2-CF 3 -6-F-phenyl,
2-MeS-phenyl, 2,6-diCl-4-MeO-phenyl,
2,3,4-triF-phenyl, 2,6-diF-4-Cl-phenyl,
2,3,4,6-tetraF-phenyl, 2,3,4,5,6-pentaF-phenyl,
2-CF 3 -4-EtO-phenyl, 2-CF 3 -4-iPrO-phenyl,
2-CF 3 -4-Cl-phenyl, 2-CF 3 -4-F-phenyl, 2-Cl-4-EtO-phenyl,
2-C-4-iPrO-phenyl, 2-Et-4-MeO-phenyl,
2-CHO-4-MeO-phenyl, 2-CH(OH)Me-4-MeO-phenyl,
2-CH(OMe)Me-4-MeO-phenyl, 2-C(═O)Me-4-MeO-phenyl,
2-CH 2 (OH)-4-MeO-phenyl, 2-CH 2 (OMe)-4-MeO-phenyl,
2-CH(OH)Et-4-MeO-phenyl, 2-C(═O)Et-4-MeO-phenyl,
(Z)-2-CH═CHCO 2 Me-4-MeO-phenyl,
2-CH 2 CH 2 CO 2 Me-4-MeO-phenyl,
(Z)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
(E)-2-CH═CHCO 2 Me-4-MeO-phenyl,
(E)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
2-CH 2 CH 2 OMe-4-MeO-phenyl,
2-F-4-MeO-phenyl, 2-Cl-4-F-phenyl,
(2-Cl-phenyl)-CH═CH—, (3-Cl-phenyl)-CH═CH—,
(2,6-diF-phenyl)-CH═CH—, —CH 2 CH═CH 2 ,
phenyl-CH═CH—, (2-Me-4-MeO-phenyl)-CH═CH—,
cyclohexyl, cyclopentyl, cyclohexylmethyl,
—CH 2 CH 2 CO 2 Et, —(CH 2 ) 3 Et, —(CH 2 ) 4 CO 2 Et,
benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl,
3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl,
2-OH-benzyl, 2-CO 2 Me-3-MeO-phenyl,
2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF 3 -4-CN-phenyl,
3-CHO-phenyl, 3-CH 2 (OH)-phenyl, 3-CH 2 (OMe)-phenyl,
3-CH 2 (NMe 2 )-phenyl, 3-CN-4-F-phenyl,
3-CONH 2 -4-F-phenyl, 2-CH 2 (NH 2 )-4-MeO-phenyl-,
phenyl-NH—, (4-F-phenyl)-NH—, (2,4-diCl-phenyl)-NH—,
phenyl-C(═O)NH—, benzyl-NH—, (2-Me-4-MeO-phenyl)-NH—,
(2-F-4-MeO-phenyl)-NH—, (2-Me-4-F-phenyl)-NH—,
phenyl-S—, —NMe 2 , 1-pyrrolidinyl, and
—N(tosylate) 2 ,
provided that two of R 7 , R 8 , and R 9 , are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
R 10A is selected from hydrogen, methyl, ethyl, benzyl, and 4-fluorobenzyl;
m is 1; and
n is 1 or 2.
8. A compound of claim 7 of Formula (IV)
wherein
b is a single bond, wherein the bridge hydrogens are in a cis position;
R 1 is selected from
hydrogen, methyl, ethyl, n-propyl, n-butyl, s-butyl,
t-butyl, n-pentyl, n-hexyl, 2-propyl, 2-butyl, 2-pentyl,
2-hexyl, 2-methylpropyl, 2-methylbutyl, 2-methylpentyl,
2-ethylbutyl, 3-methylpentyl, 3-methylbutyl,
4-methylpentyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 2-propenyl, 2-methyl-2-propenyl,
trans-2-butenyl, 3-methyl-butenyl, 3-butenyl,
trans-2-pentenyl, cis-2-pentenyl, 4-pentenyl,
4-methyl-3-pentenyl, 3,3-dichloro-2-propenyl,
trans-3-phenyl-2-propenyl, cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl, cyclopropylmethyl,
cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl,
—CH═CH 2 , —CH 2 —CH═CH 2 , —CH═CH—CH 3 , —C≡CH, —C≡C—CH 3 ,
and —CH 2 —C≡CH;
R 7 and R 9 , at each occurrence, are independently selected from hydrogen, fluoro, methyl, trifluoromethyl, and methoxy;
R 8 is selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl,
propyl, isopropyl, butyl, t-butyl, nitro,
trifluoromethyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, phenyl,
methylC(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—,
butylC(═O)—, phenylC(═O)—,
methylCO 2 —, ethylCO 2 —, propylCO 2 —, isopropylCO 2 —,
butylCO 2 —, phenylCO 2 —,
dimethylamino-S(═O)—, diethylamino-S(═O)—,
dipropylamino-S(═O)—, di-isopropylamino-S(═O)—,
dibutylamino-S(═O)—, diphenylamino-S(═O)—,
dimethylamino-SO 2 —, diethylamino-SO 2 —, dipropylamino-SO 2 —, di-isopropylamino-SO 2 —, dibutylamino-SO 2 —,
diphenylamino-SO 2 —,
dimethylamino-C(═O)—, diethylamino-C(═O)—,
dipropylamino-C(═O)—, di-isopropylamino-C(═O)—,
dibutylamino-C(═O)—, diphenylamino-C(═O)—,
2-chlorophenyl, 2-fluorophenyl, 2-bromophenyl, 2-cyanophenyl, 2-methylphenyl, 2-trifluoromethylphenyl,
2-methoxyphenyl, 2-trifluoromethoxyphenyl,
3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl,
3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl,
3-propylphenyl, 3-isopropylphenyl, 3-butylphenyl,
3-trifluoromethylphenyl, 3-methoxyphenyl,
3-isopropoxyphenyl, 3-trifluoromethoxyphenyl,
3-thiomethoxyphenyl,
4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl,
4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl,
4-propylphenyl, 4-isopropylphenyl, 4-butylphenyl,
4-trifluoromethylphenyl, 4-methoxyphenyl,
4-isopropoxyphenyl, 4-trifluoromethoxyphenyl,
4-thiomethoxyphenyl,
2,3-dichlorophenyl, 2,3-difluorophenyl, 2,3-dimethylphenyl,
2,3-ditrifluoromethylphenyl, 2,3-dimethoxyphenyl,
2,3-ditrifluoromethoxyphenyl,
2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dimethylphenyl,
2,4-ditrifluoromethylphenyl, 2,4-dimethoxyphenyl,
2,4-ditrifluoromethoxyphenyl,
2,5-dichlorophenyl, 2,5-difluorophenyl, 2,5-dimethylphenyl,
2,5-ditrifluoromethylphenyl, 2,5-dimethoxyphenyl,
2,5-ditrifluoromethoxyphenyl,
2,6-dichlorophenyl, 2,6-difluorophenyl, 2,6-dimethylphenyl, 2,6-ditrifluoromethylphenyl, 2,6-dimethoxyphenyl,
2,6-ditrifluoromethoxyphenyl,
3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl,
3,4-ditrifluoromethylphenyl, 3,4-dimethoxyphenyl,
3,4-ditrifluoromethoxyphenyl,
2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl,
2,4,6-trimethylphenyl, 2,4,6-trifluoromethylphenyl,
2,4,6-trimethoxyphenyl, 2,4,6-trifluoromethoxyphenyl,
2-chloro-4-CF 3 -phenyl, 2-fluoro-3-chloro-phenyl,
2-chloro-4-CF 3 -phenyl, 2-chloro-4-methoxy-phenyl,
2-methoxy-4-isopropyl-phenyl, 2-CF 3 -4-methoxy-phenyl,
2-methyl-4-methoxy-5-fluoro-phenyl,
2-methyl-4-methoxy-phenyl, 2-chloro-4-CF 3 O-phenyl,
2,4,5-trimethyl-phenyl, 2-methyl-4-chloro-phenyl,
methyl-C(═O)NH—, ethyl-C(═O)NH—, propyl-C(═O)NH—,
isopropyl-C(═O)NH—, butyl-C(═O)NH—, phenyl-C(═O)NH—,
4-acetylphenyl, 3-acetamidophenyl, 4-pyridyl, 2-furanyl,
2-thiophenyl, 2-naphthyl;
2-Me-5-F-phenyl, 2-F-5-Me-phenyl, 2-MeO-5-F-phenyl,
2-Me-3-Cl-phenyl, 3-NO 2 -phenyl, 2-NO 2 -phenyl,
2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl,
2-Cl-6-F-phenyl, 2-Cl-4-(CHF 2 )O-phenyl,
2,4-diMeO-6-F-phenyl, 2-CF 3 -6-F-phenyl,
2-MeS-phenyl, 2,6-diCl-4-MeO-phenyl,
2,3,4-triF-phenyl, 2,6-diF-4-Cl-phenyl,
2,3,4,6-tetraF-phenyl, 2,3,4,5,6-pentaF-phenyl,
2-CF 3 -4-EtO-phenyl, 2-CF 3 -4-iPrO-phenyl,
2-CF 3 -4-Cl-phenyl, 2-CF 3 -4-F-phenyl, 2-Cl-4-EtO-phenyl,
2-Cl-4-iPrO-phenyl, 2-Et-4-MeO-phenyl,
2-CHO-4-MeO-phenyl, 2-CH(OH)Me-4-MeO-phenyl,
2-CH(OMe)Me-4-MeO-phenyl, 2-C(═O)Me-4-MeO-phenyl,
2-CH 2 (OH)-4-MeO-phenyl, 2-CH 2 (OMe)-4-MeO-phenyl,
2-CH(OH)Et-4-MeO-phenyl, 2-C(═O)Et-4-MeO-phenyl,
(Z)-2-CH═CHCO 2 Me-4-MeO-phenyl,
2-CH 2 CH 2 CO 2 Me-4-MeO-phenyl,
(Z)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
(E)-2-CH═CHC 2 Me-4-MeO-phenyl,
(E)-2-CH═CHCH 2 (OH)-4-MeO-phenyl,
2-CH 2 CH 2 OMe-4-MeO-phenyl,
2-F-4-MeO-phenyl, 2-Cl-4-F-phenyl,
(2-Cl-phenyl)-CH═CH—, (3-Cl-phenyl)-CH═CH—,
(2,6-diF-phenyl)-CH═CH—, —CH 2 CH═CH 2 ,
phenyl-CH═CH—, (2-Me-4-MeO-phenyl)-CH═CH—,
cyclohexyl, cyclopentyl, cyclohexylmethyl,
—CH 2 CH 2 CO 2 Et, —(CH 2 ) 3 CO 2 Et, —(CH 2 ) 4 CO 2 Et,
benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl,
3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl,
2-OH-benzyl, 2-CO 2 Me-3-MeO-phenyl,
2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF 3 -4-CN-phenyl,
3-CHO-phenyl, 3-CH 2 (OH)-phenyl, 3-CH 2 (OMe)-phenyl,
3-CH 2 (NMe 2 )-phenyl, 3-CN-4-F-phenyl,
3-CONH 2 -4-F-phenyl, 2-CH 2 (NH 2 )-4-MeO-phenyl-,
phenyl-NH—, (4-F-phenyl)-NH—, (2,4-diCl-phenyl)-NH—,
phenyl-C(═O)NH—, benzyl-NH—, (2-Me-4-MeO-phenyl)-NH—,
(2-F-4-MeO-phenyl)-NH—, (2-Me-4-F-phenyl)-NH—,
phenyl-S—, —NMe 2 , 1-pyrrolidinyl, and
—N(tosylate) 2 ;
R 10A is selected from hydrogen, methyl, ethyl, 4-fluorobenzyl and benzyl; and
n is 1 or 2.
9. A compound of claim 1 wherein:
X is —NR 10A —;
R 1 is selected from
C 1-6 alkyl substituted with Z,
C 2-6 alkenyl substituted with Z,
C 2-6 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-6 alkyl substituted with 0-2 R 2 ,
C 2-6 alkenyl substituted with 0-2 R 2 ,
C 2-6 alkynyl substituted with 0-2 R 2 ,
aryl substituted with 0-2 R 2 , and
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with 0-2 R 2 ,
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—OC(O)R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ,
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0-5 R 42 ,
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 3 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H, methyl, ethyl, propyl, or butyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, and
aryl substituted with 0-3 R 44 ;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —CN, —NO 2 , —NR 46 R 47 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy, (C 1-4 haloalkyl)oxy,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O) NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 ) NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O) R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O)NHR 15 ;
R 10A is selected from H,
C 1-6 alkyl substituted with 0-1 R 10B ,
C 2-6 alkenyl substituted with 0-1 R 10B ,
C 2-6 alkynyl substituted with 0-1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
phenyl substituted with 0-3 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —CN, —NO 2 ,
C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 haloalkyl, C 1-8 alkoxy C 3-10 cycloalkyl,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O) NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , OC(O)OR 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 ) NR 12 R 13 , S(O)R12, S(O) 2 R 12 , S(O)NR 12 R 13 , S(O) 2 NR 12 R 13 , NR 14 S(O)R 15 , and NR 14 S(O) 2 R 12 ,
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 31 , at each occurrence, is independently selected from
H, OH, halo, CF 3 , SO 2 R 45 , NR 46 R 47 , methyl, ethyl, and propyl;
R 33 , at each occurrence, is independently selected from
H, OH, halo, CN, NO 2 , CF 3 , SO 2 R 45 , NR 46 R 47 ,
C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 3-5 cycloalkyl, C 1-3 haloalkyl, C 1-3 haloalkyl-oxy-, C 1-3 alkyloxy-, C 1-3 alkylthio-, C 1-3 alkyl-C(═O)—, and C 1-3 alkyl-C(═O)NH—;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 ,
C 1-4 alkyl, and C 1-4 alkoxy;
R 45 is C 1-4 alkyl;
R 46 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 47 , at each occurrence, is independently selected from H,
C 1-4 alkyl, —C(═O)NH(C 1-4 alkyl), —SO 2 (C 1-4 alkyl),
—SO 2 (phenyl), —C(═O)O(C 1-4 alkyl), —C(═O) (C 1-4 alkyl),
and —C(═O)H;
R 48 , at each occurrence, is independently selected from H,
C 1-4 alkyl, —C(═O)NH(C 1-4 alkyl), —C(═O)O(C 1-4 alkyl),
—C(═O)(C 1-4 alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, or 2; and
n is 1 or 2.
10. A compound of claim 9 wherein:
X is —NR 10A —;
R 1 is selected from
C 2-5 alkyl substituted with Z,
C 2-5 alkenyl substituted with Z,
C 2-5 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group consisting of N, O, and S, said heterocyclic ring system substituted with Z;
C 1-5 alkyl substituted with 0-2 R 2 ,
C 2-5 alkenyl substituted with 0-2 R 2 , and
C 2-5 alkynyl substituted with 0-2 R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3,
—NR 3 C(O)R 2 ,
—C(O) OR 2 ,
—OC(O)R 2 ,
—CH(═NR 4 )NR 2 R 3 ,
—NHC(═NR 4 )NR 2 R 3 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
aryl substituted with 0-5 R 42 ;
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 3 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H, methyl, or ethyl;
R 6a is selected from
H, —OH, —NR 46 R 47 , —CF 3 ,
C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, and C 3-6 cycloalkyl;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy, (C 1-4 haloalkyl)oxy,
C 1-4 alkyl substituted with 0-2 R 11 ,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O) NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13 , S(O)R 12 , S(O) 2 R 12 , S(O) 2 NR 12 R 13 , NR 14 S(O) 2 R 12 , NR 14 S(O)R 12 , NR 14 S(O) 2 R 12 , NR 12 C(O)R 15 , NR 12 C(O)OR 15 , NR 12 S(O) 2 R 15 , and NR 12 C(O) NHR 15 ,
R 10A is selected from H,
C 1-6 alkyl substituted with 0-1 R 10B ,
C 2-6 alkenyl substituted with 0-1 R 10B ,
C 2-6 alkynyl substituted with 0-1 R 10B , and
C 1-6 alkoxy;
R 10B is selected from
C 1-4 alkoxy,
C 3-6 cycloalkyl,
C 3-6 carbocyclic group substituted with 0-3 R 33 ,
phenyl substituted with 0-3 R 33 , and
5-6 membered heterocyclic ring system containing 1, 2, or 3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R 44 ;
R 11 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 , —NR 46 R 47 ,
C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, C 1-6 alkoxy (C 1-4 haloalkyl)oxy,
C 3-10 carbocyclic group substituted with 0-3 R 33 ,
aryl substituted with 0-5 R 33 ,
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
OR 12 , SR 12 , NR 12 R 13 , C(O)H, C(O)R 12 , C(O) NR 12 R 13 , NR 14 C(O)R 12 , C(O)OR 12 , OC(O)R 12 , CH(═NR 14 )NR 12 R 13 , NHC(═NR 14 )NR 12 R 13.S(O)R12 , S(O) 2 R 12 , S(O) 2 NR 12 R 13 , and NR 14 S (O) 2 R 12 ;
R 12 , at each occurrence, is independently selected from
C 1-4 alkyl,
C 2-4 alkenyl,
C 2-4 alkynyl,
C 3-6 cycloalkyl,
phenyl substituted with 0-5 R 33 ;
C 3-10 carbocyclic group substituted with 0-3 R 33 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 31 ;
R 13 , at each occurrence, is independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl;
alternatively, R 12 and R 13 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 14 )—;
R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;
R 31 , at each occurrence is independently selected from H, OH, halo, CF 3 , methyl, and ethyl;
R 33 , at each occurrence, is independently selected from H, OH, halo, CN, NO 2 , CF 3 , methyl, and ethyl;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O,
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is C 3-6 cycloalkyl or aryl substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H, halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —CF 3 , —OCF 3 , —CN, —NO 2 , C 1-4 alkyl and C 1-4 alkoxy;
R 45 is C 1-4 alkyl
R 46 , at each occurrence, is independently selected from H and C 1-3 alkyl;
R 47 , at each occurrence, is independently selected from H,
C 1-4 alkyl, —C(═O)NH(C 1-4 alkyl), —SO 2 (C 1-4 alkyl),
—SO 2 (phenyl), —C(═O)O(C 1-4 alkyl), —C(═O) (C 1-4 alkyl),
and —C(═O)H;
R 48 , at each occurrence, is independently selected from H,
C 1-4 alkyl, —C(═O)NH(C 1-4 alkyl), —C(═O)O(C 1-4 alkyl),
—C(═O)(C 1-4 alkyl), and —C(═O)H;
k is 1 or 2;
m is 0, 1, 2; and
n is 1 or 2.
11. A compound of claim 9 wherein:
X is —NR 10A —;
R 1 is selected from
C 2-4 alkyl substituted with Z,
C 2-4 alkenyl substituted with Z,
C 2-4 alkynyl substituted with Z,
C 3-6 cycloalkyl substituted with Z,
aryl substituted with Z,
5-6 membered heterocyclic ring system containing at least one heteroatom selected from the group containing of N, O, and S, said heterocyclic ring system substituted with Z;
C 2-4 alkyl substituted with 0-2 R 2 ; and
C 2-4 alkenyl substituted with 0-2 R 2 ;
Z is selected from H,
—CH(OH)R 2 ,
—C(ethylenedioxy)R 2 ,
—OR 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R;
R 2 , at each occurrence, is independently selected from phenyl substituted with 0-5 R 42 ,
C 3-10 carbocyclic group substituted with 0-3 R 41 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 41 ;
R 3 , at each occurrence, is independently selected from
H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 alkoxy;
alternatively, R 2 and R 3 join to form a 5- or 6-membered ring optionally substituted with —O— or —N(R 4 )—;
R 4 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 5 is H;
R 6a is selected from H, —OH, —CF 3 , methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, (C 1-3 haloalkyl) oxy, and
C 1-4 alkyl substituted with 0-2 R 11 ;
R 10A is selected from H, C 1-6 alkyl, C 1-4 alkoxy and C 1-2 alkyl substituted with 0-1 R 10B ;
R 10B is C 3-6 cycloalkyl or phenyl substituted with 0-3 R 33 ;
R 11 is selected from
H, halo, —CF 3 , —OCF 3 , —OH, —OCH 3 , —CN, —NO 2 ,
C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, and (C 1-3 haloalkyl)oxy;
R 33 , at each occurrence, is independently selected from H, OH, halo, CF 3 , and methyl;
R 41 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CF 2 H, SO 2 R 45 , NR 46 R 47 , NO 2 , CN, ═O.
C 2-8 alkenyl, C 2-8 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 42 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 42 , at each occurrence, is independently selected from
H, CF 3 , halo, OH, CO 2 H, SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 , CN, CH(═NH)NH 2 , NHC(═NH)NH 2 ,
C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl,
C 1-4 alkyl substituted with 0-1 R 43 ,
aryl substituted with 0-3 R 44 , and
5-10 membered heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R 44 ;
R 43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R 44 ;
R 44 , at each occurrence, is independently selected from H,
halo, —OH, NR 46 R 47 , CO 2 H, SO 2 R 45 , —SF 3 , —OCF 3 , —CN, —NO 2 ,
methyl, ethyl, propyl, butyl, methoxy, ethoxy,
propoxy, and butoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, n-butyl,
i-butyl, —C(═O)NH(methyl), —C(═O)NH(ethyl),
—SO 2 (methyl), —SO 2 (ethyl), —SO 2 (phenyl),
—C(═O)O(methyl), —C(═O)O(ethyl), —C(═O) (methyl),
—C(═O)(ethyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, —C(═O)NH (methyl), —C(═O)NH(ethyl), —C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl), —C(═O) (ethyl), and —C(═O)H;
k is 1;
m is 0, 1, or 2; and
n is 1 or 2.
12. A compound of claim 9 wherein:
X is —NH—;
R 1 is selected from
ethyl substituted with Z,
propyl substituted with Z,
butyl substituted with Z,
propenyl substituted with Z,
butenyl substituted with Z,
ethyl substituted with R 2 ,
propyl substituted with R 2 ,
butyl substituted with R 2 ,
propenyl substituted with R 2 and
butenyl substituted with R 2 ;
Z is selected from H,
—HC(OH)R 2 ,
—SR 2 ,
—NR 2 R 3 ,
—C(O)R 2 ,
—C(O)NR 2 R 3 ,
—NR 3 C(O)R 2 ,
—C(O)OR 2 ,
—S(O)R 2 ,
—S(O) 2 R 2 ,
—S(O) 2 NR 2 R 3 , and —NR 3 S(O) 2 R 2 ;
R 2 , at each occurrence, is independently selected from
phenyl substituted with 0-3 R 42 ;
naphthyl substituted with 0-3 R 42 ;
cyclopropyl substituted with 0-3 R 41 ;
cyclobutyl substituted with 0-3 R 41 ;
cyclopentyl substituted with 0-3 R 41 ;
cyclohexyl substituted with 0-3 R 41 ;
pyridyl substituted with 0-3 R 41 ;
indolyl substituted with 0-3 R 41 ;
indolinyl substituted with 0-3 R 41 ;
benzimidazolyl substituted with 0-3 R 41 ;
benzotriazolyl substituted with 0-3 R 41 ;
benzothienyl substituted with 0-3 R 41 ;
benzofuranyl substituted with 0-3 R 41 ;
phthalimid-1-yl substituted with 0-3 R 41 ;
inden-2-yl substituted with 0-3 R 41 ;
2,3-dihydro-1H-inden-2-yl substituted with 0-3 R 41 ;
indazolyl substituted with 0-3 R 41 ;
tetrahydroquinolinyl substituted with 0-3 R 41 ; and
tetrahydro-isoquinolinyl substituted with 0-3 R 41 ;
R 3 , at each occurrence, is independently selected from H, methyl, and ethyl;
R 5 is H;
R 6a is selected from H, —OH, methyl, and methoxy;
R 6b is H;
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from H, F, Cl, methyl, ethyl, methoxy, —CF 3 , and —OCF 3 ;
R 41 , at each occurrence, is independently selected from
H, F, Cl, Br, OH, CF 3 , NO 2 , CN, ═O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R 42 , at each occurrence, is independently selected from
H, F, Cl, Br, OH, CF 3 , SO 2 R 45 , SR 45 , NR 46 R 47 , OR 48 , NO 2 ,
CN, ═O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R 45 is methyl, ethyl, propyl, or butyl;
R 46 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R 47 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, n-butyl,
i-butyl, —C(═O)NH(methyl), —C(═O)NH(ethyl),
—SO 2 (methyl), —SO2(ethyl), —SO2(phenyl),
—C(═O)O(methyl), —C(═O)O(ethyl), —C(═O) (methyl),
—C(═O)(ethyl), and —C(═O)H;
R 48 , at each occurrence, is independently selected from
H, methyl, ethyl, n-propyl, i-propyl, —C(═O)NH (methyl), —C(═O)NH(ethyl), —C(═O)O(methyl), —C(═O)O(ethyl), —C(═O)(methyl), —C(═O) (ethyl), and —C(═O)H;
k is 1;
m is 0, 1, or 2; and
n is 1 or 2.
13. A compound of claim 9 of Formula (I-a)
wherein:
b is a single bond;
X is —NR 10A —;
R 1 is selected from
—(CH 2 ) 3 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-bromo-phenyl),
—(CH 2 ) 3 C(═O)(4-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-methoxy-phenyl),
—(CH 2 ) 3 C(═O)(4-(3,4-dichloro-phenyl)phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-4-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 C(═O)(phenyl),
—(CH 2 )3C(═O)(4-chloro-phenyl),
—(CH 2 ) 3 C(═O)(3-methyl-phenyl),
—(CH 2 ) 3 C(═O)(4-t-butyl-phenyl),
—(CH 2 ) 3 C(═O)(3,4-difluoro-phenyl),
—(CH 2 ) 3 C(═O)(2-methoxy-5-fluoro-phenyl),
—(CH 2 ) 3 C(═O)(4-fluoro-1-naphthyl),
—(CH 2 ) 3 C(═O)(benzyl),
—(CH 2 ) 3 C(═O)(4-pyridyl),
—(CH 2 ) 3 C(═O)(3-pyridyl),
—(CH 2 ) 3 CH(OH(4-fluoro-phenyl),
—(CH 2 ) 3 CH(OH)(4-pyridyl),
—(CH 2 ) 3 CH(OH)(2,3-dimethoxy-phenyl),
—(CH 2 ) 3 S(3-fluoro-phenyl),
—(CH 2 ) 3 S(4-fluoro-phenyl),
—(CH 2 ) 3 S(═O)(4-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (3-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (4-fluoro-phenyl),
—(CH 2 ) 3 O(4-fluoro-phenyl),
—(CH 2 ) 3 O(phenyl),
—(CH 2 ) 3 O(3-pyridyl),
—(CH 2 ) 3 O(4-pyridyl),
—(CH 2 ) 3 O(2-NH 2 -phenyl),
—(CH 2 ) 3 O(2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-OH-phenyl),
—(CH 2 ) 3 O(2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 O(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 O(2-NHC(═O)Me-phenyl),
—(CH 2 ) 3 NH(4-fluoro-phenyl),
—(CH 2 ) 3 N (methyl)(4-fluoro-phenyl),
—(CH 2 ) 3 CO 2 (ethyl),
—(CH 2 ) 3 C(═O)N(methyl)(methoxy),
—(CH 2 ) 3 C(═O)NH(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(phenyl),
—(CH 2 2 NMeC(═O)(phenyl),
—(CH 2 ) 2 NHC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O)(2,4-difluoro-phenyl),
—(CH 2 ) 2 NMeC(═O)(2,4-difluoro-phenyl),
—(CH 2 3 (3-indolyl),
—(CH 2 ) 3 (1-methyl-3-indolyl),
—(CH 2 ) 3 (1-indolyl),
—(CH 2 ) 3 (1-indolinyl),
—(CH 2 ) 3 (1-benzimidazolyl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 3 (3,4 dihydro-1(2H)-quinolinyl),
—(CH 2 ) 2 C(═O)(4-fluoro-phenyl),
—(CH 2 ) 2 C(═O)NH(4-fluoro-phenyl),
—CH 2 CH 2 (3-indolyl),
—CH 2 CH 2 (1-phthalimidyl),
—(CH 2 ) 4 C(═O)N(methyl)(methoxy),
—(CH 2 ) 4 CO 2 (ethyl),
—(CH 2 ) 4 C(═O)(phenyl),
—(CH 2 ) 4 (cyclohexyl),
—(CH 2 ) 3 CH(phenyl) 2 ,
—CH 2 CH 2 CH═C(phenyl) 2 ,
—CH 2 CH 2 CH═CMe(4-F-phenyl),
—(CH 2 ) 3 CH(4-fluoro-phenyl) 2 ,
—CH 2 CH 2 CH═C(4-fluoro-phenyl) 2 ,
—(CH 2 ) 2 (2,3-dihydro-1H-inden-2-yl),
—(CH 2 ) 3 C(═O)(2-NH 2 -phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-OH-phenyl),
—(CH 2 ) 3 C(═O)(2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 (1H-indazol-3-yl),
—(CH 2 ) 3 (5-F-1H-indazol-3-yl),
—(CH 2 ) 3 (7-F-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Cl-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Br-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHMe-phenyl),
—(CH 2 ) 3 (1-benzothien-3-yl),
—(CH 2 ) 3 (6-F-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (9H-purin-9-yl),
—(CH 2 ) 3 (7H-purin-7-yl),
—(CH 2 ) 3 (6-F-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)Me-phenyl),
—(CH 2 ) 3 C(═O)(2-NHCO 2 Et-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHC(═O)NHEt-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHCHO-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-OH-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-MeS-4-F-phenyl),
—(CH 2 ) 3 C(═O)(2-NHSO 2 Me-4-F-phenyl),
—(C 2 ) 2 C(Me)CO 2 Me,
—(CH 2 ) 2 C(Me)CH(OH)(4-F-phenyl) 2 ,
—(CH 2 ) 2 C(Me)CH(OH)(4-Cl-phenyl) 2 ,
—(CH 2 ) 2 C(Me)C(═O)(4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-MeO-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(3-Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O)(2-Me-phenyl),
—(CH 2 ) 2 C(Me) C(═O)phenyl,
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from
hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl,
propyl, isopropyl, butyl, t-butyl, nitro,
trifluoromethyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, phenyl, benzyl,
HC(═O)—, methylC(═O)—, ethylC(═O)—, propylC(═O)—,
isopropylC(═O)—, n-butylC(═O)—, isobutylC (═O)—,
secbutylC(═O)—, tertbutylC(═O)—, phenylC (═O)—,
methylC(═O)NH—, ethylC(═O)NH—, propylC (═O)NH—,
isopropylC(═O)NH—, n-butylC(═O)NH—, isobutylC(═O)NH—,
secbutylC(═O)NH—, tertbutylC(═O)NH—, phenylC(═O)NH—,
methylamino-, ethylamino-, propylamino-, isopropylamino-,
n-butylamino-, isobutylamino-, secbutylamino-,
tertbutylamino-, phenylamino-,
provided that two of substituents R 7 , R 8 , and R 9 , are
independently selected from hydrogen, fluoro, chloro,
bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl,
nitro, trifluoromethyl, methoxy, ethoxy,
isopropoxy, and trifluoromethoxy;
R 10A is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, benzyl, 2-chlorobenzyl, 2-fluorobenzyl, 2-bromobenzyl, 2-methylbenzyl, 2-trifluoromethylbenzyl, 2-methoxybenzyl, 2-trifluoromethoxybenzyl, 3-chlorobenzyl, 3-fluorobenzyl, 3-bromobenzyl, 3-methylbenzyl, 3-trifluoromethylbenzyl, 3-methoxybenzyl, 3-trifluoromethoxybenzyl, 4-chlorobenzyl, 4-fluorobenzyl, 4-bromobenzyl, 4-methylbenzyl, 4-trifluoromethylbenzyl, 4-methoxybenzyl, and 4-trifluoromethoxybenzyl;
k is 1 or 2;
m is 1 or 2; and
n is 1 or 2.
14. A compound of claim 13 of Formula (IV-a)
wherein:
b is a single bond, wherein the bridge hydrogens are in a cis position;
R 1 is selected from
—(CH 2 ) 3 C(═O) (4-fluoro-phenyl),
—(CH 2 ) 3 C(═O) (4-bromo-phenyl),
—(CH 2 )3C(═O) (4-methyl-phenyl),
—(CH 2 ) 3 C(═O) (4-methoxy-phenyl),
—(CH 2 ) 3 C(═O)(4-(3,4-dichloro-phenyl)phenyl),
—(CH 2 ) 3 C(═O) (3-methyl-4-fluoro-phenyl),
—(CH 2 ) 3 C(═O) (2,3-dimethoxy-phenyl),
—(CH 2 ) 3 C(═O) (phenyl),
—(CH 2 ) 3 C(═O) (4-chloro-phenyl),
—(CH 2 ) 3 C(═O) (3-methyl-phenyl),
—(CH 2 ) 3 C(═O) (4t-butyl-phenyl),
—(CH 2 ) 3 C(═O) (3,4-difluoro-phenyl),
—(CH 2 ) 3 C(═O) (2-methoxy-5-fluoro-phenyl),
—(CH 2 ) 3 C(═O) (4-fluoro-1-naphthyl),
—(CH 2 ) 3 C(═O) (benzyl),
—(CH 2 ) 3 C(═O) (4-pyridyl),
—(CH 2 ) 3 C(═O) (3-pyridyl),
—(CH 2 ) 3 CH(OH) (4-fluoro-phenyl),
—(CH 2 ) 3 CH(OH) (4-pyridyl),
—(CH 2 ) 3 CH(OH) (2,3-dimethoxy-phenyl),
—(CH 2 ) 3 S(3-fluoro-phenyl),
—(CH 2 ) 3 S(4-fluoro-phenyl),
—(CH 2 ) 3 S(═O) (4-fluoro-phenyl),
—(CH 2 ) 3 SO 2 (3-fluoro-phenyl),
—(CH 2 ) 3 SO 2 ) (4-fluoro-phenyl),
—(CH 2 ) 3 O(4-fluoro-phenyl),
—(CH 2 ) 3 O(phenyl),
—(CH 2 ) 3 NH(4-fluoro-phenyl),
—(CH 2 ) 3 N(methyl) (4-fluoro-phenyl),
—(CH 2 ) 3 CO 2 (ethyl),
—(CH 2 ) 3 C(═O)N(methyl) (methoxy),
—(CH 2 ) 3 C(═O)NH(4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O) (phenyl),
—(CH 2 ) 2 NMeC(═O) (phenyl),
—(CH 2 ) 2 NHC(═O) (2-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O) (2-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O) (4-fluoro-phenyl),
—(CH 2 ) 2 NMeC(═O) (4-fluoro-phenyl),
—(CH 2 ) 2 NHC(═O) (2,4-difluoro-phenyl),
—(CH 2 ) 2 NMeC(═O) (2,4-difluoro-phenyl),
—(CH 2 ) 3 (3-indolyl)
—(CH 2 )3(1-methyl-3-indolyl),
—(CH 2 ) 3 (1-indolyl),
—(CH 2 ) 3 (1-indolinyl),
—(CH 2 ) 3 (1-benzimidazolyl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-1-yl),
—(CH 2 ) 3 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-1-yl)
—(CH 2 ) 2 (1H-1,2,3-benzotriazol-2-yl),
—(CH 2 ) 3 (3,4 dihydro-1(2H)-quinolinyl),
—(CH 2 ) 2 C(═O) (4-fluoro-phenyl),
—(CH 2 ) 2 C(═O)NH(4-fluoro-phenyl),
—CH 2 CH 2 (3-indolyl),
—CH 2 CH 2 (1-phthalimidyl),
—(CH 2 ) 4 C(═O)N(methyl)(methoxy),
—(CH 2 ) 4 CO 2 (ethyl),
—(CH 2 ) 4 C(═O) (phenyl),
—(CH 2 ) 4 (cyclohexyl),
—(CH 2 ) 3 CH(phenyl) 2 ,
—CH 2 CH 2 CH═C(phenyl) 2 ,
—CH 2 CH 2 CH═CMe(4-F-phenyl),
—(CH 2 ) 3 CH(4-fluoro-phenyl) 2 ,
—CH 2 CH 2 CH═C(4-fluoro-phenyl) 2 ,
—(CH 2 ) 2 (2,3-dihydro-1H-inden-2-yl),
—(CH 2 ) 3 C(═O) (2-NH 2 -phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -5-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -3-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -4-Cl-phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -4-OH-phenyl),
—(CH 2 ) 3 C(═O) (2-NH 2 -4-Br-phenyl),
—(CH 2 ) 3 (1H-indazol-3-yl),
—(CH 2 ) 3 (5-F-1H-indazol-3-yl),
—(CH 2 ) 3 (7-F-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Cl-1H-indazol-3-yl),
—(CH 2 ) 3 (6-Br-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O) (2-NHMe-phenyl),
—(CH 2 ) 3 (1-benzothien-3-yl),
—(CH 2 ) 3 (6-F-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (5-F-2,3-dihydro-1H-indol-1-yl),
—(CH 2 ) 3 (6-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (5-F-1H-indol-3-yl),
—(CH 2 ) 3 (9H-purin-9-yl),
—(CH 2 ) 3 (7H-purin-7-yl),
—(CH 2 ) 3 (6-F-1H-indazol-3-yl),
—(CH 2 ) 3 C(═O) (2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHC(═O)Me-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHCO 2 Et-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHC(═O)NHEt-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHCHO-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-OH-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-MeS-4-F-phenyl),
—(CH 2 ) 3 C(═O) (2-NHSO 2 Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)CO 2 Me,
—(CH 2 ) 2 C(Me)CH(OH) (4-F-phenyl) 2
—(CH 2 ) 2 C(Me)CH(OH) (4-Cl-phenyl) 2 ,
—(CH 2 ) 2 C(Me)C(═O) (4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O) (2-MeO-4-F-phenyl)
—(CH 2 ) 2 C(Me)C(═O) (3-Me-4-F-phenyl),
—(CH 2 ) 2 C(Me)C(═O) (2-Me-phenyl),
—(CH 2 ) 2 C(Me)C(═O) phenyl,
R 7 , R 8 , and R 9 , at each occurrence, are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylCO(═O)—, ethylC(═O)—, propylC(═O)—, isopropylC(═O)—, methylC(═O) NH—, ethylC(═O)NH—, propylC(═O)NH—, isopropylC(═O)NH, methylamino-, ethylamino-, propylamino-, and isopropylamino-,
provided that two of substituents R 7 , R 8 , and R 9 , are independently selected from hydrogen, fluoro, chloro, methyl, trifluoromethyl, methoxy, and trifluoromethoxy;
R 10A is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, benzyl, 2-chlorobenzyl, 2-fluorobenzyl, 2-bromobenzyl, 2-methylbenzyl, 2-trifluoromethylbenzyl, 2-methoxybenzyl, 2-trifluoromethoxybenzyl, 3-chlorobenzyl, 3-fluorobenzyl, 3-bromobenzyl, 3-methylbenzyl, 3-trifluoromethylbenzyl, 3-methoxybenzyl, 3-trifluoromethoxybenzyl, 4-chlorobenzyl, 4-fluorobenzyl, 4-bromobenzyl, 4-methylbenzyl, 4-trifluoromethylbenzyl, 4-methoxybenzyl, and 4-trifluoromethoxybenzyl;
m is 1 or 2; and
n is 1 or 2.
15. A compound of selected from the group consisting of
4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′: 4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-pyridinyl)-1-butanone hydrochloride;
(6bR, 10aS)-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′, 4′: 4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′, 4′: 4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
(6bR, 10aS)-8-[3-(6-fluoro-1,2-benzisoxazol-3-yl) propyl]-3-methyl-2,3,6b, 7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline hydrochloride;
(6bR, 10aS)-8-[3-(1,2-benzisoxazol-3-yl)propyl]-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′, 4′: 4,5]pyrrolo[1,2,3-de]quinoxaline hydrochloride;
(6bR, 10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′, 4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-3-ethyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-3-propyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-3-is propyl-2,3,6b, 7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-3-butyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-3-benzyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((6bR, 10aS)-3-ethyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((6bR, 10aS)-3-isopropyl-2,3,6b9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8 (7H)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((6bR, 10aS)-3-benzyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
(6bR, 10aS)-8-[3:(4-fluorophenoxy)propyl]-3-methyl-2, 3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′, 4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-5-(2,4dichlorophenyl)-3-methyl-2,3,6b,7,8 9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline;
(6bR, 10aS)-5-(2,4-dichlorophenyl)-2,3,6b, 7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de] quinoxaline hydrochloride;
4-((6bR, 10aS)-5-bromo-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de] quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((6bR, 10aR)-5-methoxy-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de] quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone;
(8aS, 12aR)-2-(2,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12, 12a-decahydro[1,4]diazepino[3,2,1-hi]pyrido(4,3-b]indole hydrochloride;
(8aS, 12aR)-2-(4-methoxy-2-methylphenyl)-4,5,6,7,8a,9, 10,11,12,12a-decahydro[1,4]diazepino[3,2,1-hi]pyrido [4,3-b]indole hydrochloride;
(6bS, 11aS)-3-methyl-2,3,7,8,9,10,11,11a-octahydro-1H, 6bH-azepino[4′:5′, 4,5]pyrrolo[1,2,3-de]quinoxaline;
(4-(3-methyl-2,3,6b,7,8,10,11,11a-octahydro-1H,9H-azepino[4′,5′:4,5]pyrrolo[1,2,3-de]quinoxalin-9-yl)-1-(4-fluorophenyl)-1-butanone; and
(+/−)-1,1,3-Trimethyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline.
16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , or 15 , or a pharmaceutically acceptable salt thereof.
17. A method for treating a human suffering from a disorder associated with 5HT2C receptor modulation selected from obesity, anorexia, bulemia, depression, a anxiety, psychosis, schizophrenia, migraine, obsessive-compulsive disorder, and sexual disorders; comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , or 8 or a pharmaceutically acceptable salt thereof.
18. A method for treating a human suffering from a disorder associated with 5HT2A receptor modulation selected from depression, psychosis, schizophrenia, migraine, attention deficit disorder, attention deficit hyperactivity disorder, and obsessive-compulsive disorder; comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , 9 , 10 , 11 , 12 , 13 , or 14 ; or a pharmaceutically acceptable salt thereof.
19. A method for treating obesity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , or 8 , or a pharmaceutically acceptable salt thereof.
20. A method for treating schizophrenia comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , or 14 or a pharmaceutically acceptable salt thereof.
21. A method for treating depression comprising administering to a patient a need thereof a therapeutically effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , or 14 , or a pharmaceutically acceptable salt thereof.Cited by (0)
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