Substituted heterocycle fused gamma-carbolines
First Claim
1. A compound of the formula (I):
-
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein;
b is a single bond;
X is —
CHR10—
or —
C(═
O)—
;
R1 is selected from H, C(═
O)R2, C(═
O)OR2, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-7 cycloalkyl, C1-6 alkyl substituted with Z, C2-6 alkenyl substituted with Z, C2-6 alkynyl substituted with Z, C3-6 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;
C1-3 alkyl substituted with Y, C2-3 alkenyl substituted with Y, C2-3 alkynyl substituted with Y, C1-6 alkyl substituted with 0-2 R2, C2-6 alkenyl substituted with 0-2 R2, C2-6 alkynyl substituted with 0-2 R2, aryl substituted with 0-2 R2, 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 R2;
Y is selected from C3-6 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;
C3-6 cycloalkyl substituted with —
(C1-3 alkyl)-Z, aryl substituted with —
(C1-3 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 —
(C1-3 alkyl)-Z;
Z is selected from H, —
CH(OH)R2, —
C(ethylenedioxy)R2, —
OR2, —
SR2, —
NR2R3, —
C(O)R2, —
C(O)NR2R3, —
NR3C(O)R2, —
C(O)OR2, —
OC(O)R2, —
CH(═
NR4)NR2R3, —
NHC(═
NR4)NR2R3, —
S(O)R2, —
S(O)2R2, —
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from halo, C1-3 haloalkyl, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, aryl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R3, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkoxy;
alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R4)—
;
R4, at each occurrence, is independently selected from H and C1-4 alkyl;
R5 is H or C1-4 alkyl;
R6a and R6b, at each occurrence, are independently selected from H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, and aryl substituted with 0-3 R44;
R7 and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R8 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH, C1-6 alkyl substituted with 0-1 R10B, C2-6 alkenyl substituted with 0-1 R10B, C2-6 alkynyl substituted with 0-1 R10B, and C1-6 alkoxy;
R10B is selected from C1-4 alkoxy, C3-6 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, phenyl substituted with 0-3 R33, 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 R44;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl, alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14);
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H and C1-4 alkyl;
R15, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
R16, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-3 haloalkyl-oxy-, and C1-3 alkyloxy-;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, SO2R45, NR46R47, and C1-4 alkyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, ═
O;
C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, SOR45, SR45, NR46SO2R45, NR46COR45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-4 alkyl;
R47, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
SO2(C1-4 alkyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
k is 1 or 2;
m is 0, 1, or 2;
n is 0, 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;
provided that when R6 or R6a is NH2, then X is not —
CH(R10); and
provided that when n=0, then R6 or R6a is not NH2 or —
OH.
3 Assignments
0 Petitions
Accused Products
Abstract
The present invention is directed to certain novel compounds represented by structural Formula (I)
or pharmaceutically acceptable salt forms thereof, wherein R1, R5, R6a, R6b, R7, R8, R9, 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.
-
Citations
23 Claims
-
1. A compound of the formula (I):
-
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein; b is a single bond;
X is —
CHR10—
or —
C(═
O)—
;
R1 is selected from H, C(═
O)R2,C(═
O)OR2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-7 cycloalkyl, C1-6 alkyl substituted with Z, C2-6 alkenyl substituted with Z, C2-6 alkynyl substituted with Z, C3-6 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;
C1-3 alkyl substituted with Y, C2-3 alkenyl substituted with Y, C2-3 alkynyl substituted with Y, C1-6 alkyl substituted with 0-2 R2, C2-6 alkenyl substituted with 0-2 R2, C2-6 alkynyl substituted with 0-2 R2, aryl substituted with 0-2 R2, 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 R2;
Y is selected from C3-6 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;
C3-6 cycloalkyl substituted with —
(C1-3 alkyl)-Z,aryl substituted with —
(C1-3 alkyl)-Z, and5-6 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 —
(C1-3 alkyl)-Z;
Z is selected from H, —
CH(OH)R2,—
C(ethylenedioxy)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O)NR2R3,—
NR3C(O)R2,—
C(O)OR2,—
OC(O)R2,—
CH(═
NR4)NR2R3,—
NHC(═
NR4)NR2R3,—
S(O)R2,—
S(O)2R2,—
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from halo, C1-3 haloalkyl, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, aryl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R3, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkoxy;
alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R4)—
;
R4, at each occurrence, is independently selected from H and C1-4 alkyl;
R5 is H or C1-4 alkyl;
R6a and R6b, at each occurrence, are independently selected from H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, andaryl substituted with 0-3 R44;
R7 and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R8 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH,C1-6 alkyl substituted with 0-1 R10B, C2-6 alkenyl substituted with 0-1 R10B, C2-6 alkynyl substituted with 0-1 R10B, and C1-6 alkoxy;
R10B is selected from C1-4 alkoxy, C3-6 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, phenyl substituted with 0-3 R33, 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 R44;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl, alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14);
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H and C1-4 alkyl;
R15, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
R16, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-3 haloalkyl-oxy-, and C1-3 alkyloxy-;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, SO2R45, NR46R47, and C1-4 alkyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, ═
O;
C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, SOR45, SR45, NR46SO2R45, NR46COR45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-4 alkyl;
R47, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
SO2(C1-4 alkyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
k is 1 or 2;
m is 0, 1, or 2;
n is 0, 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;
provided that when R6 or R6a is NH2, then X is not —
CH(R10); and
provided that when n=0, then R6 or R6a is not NH2 or —
OH.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)
X is —
CHR10—
or —
C(═
O)—
;
R1 is selected from H, C(═
O)R2,C(═
O)OR2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-7 cycloalkyl, C1-6 alkyl substituted with 0-2 R2, C2-6 alkenyl substituted with 0-2 R2, C2-6 alkynyl substituted with 0-2 R2, aryl substituted with 0-2 R2, 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 R2;
R2, at each occurrence, is independently selected from F, Cl, CH2F, CHF2, CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is selected from H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, andaryl substituted with 0-3 R44;
R6b is H;
R7 and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R8 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH,C1-6 alkyl substituted with 0-1 R10B, C2-6 alkenyl substituted with 0-1 R10B, C2-6 alkynyl substituted with 0-1 R10B, and C1-6 alkoxy;
R10B is selected from C1-4 alkoxy, C3-6 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, phenyl substituted with 0-3 R33, 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 R44;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H and C1-4 alkyl;
R15, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
R16, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, —
C1-4 haloalkyl, C1-3 haloalkyl-oxy-, and C1-3 alkyloxy-;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, SO2R45, NR46R47, and C1-4 alkyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN;
C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-4 alkyl;
R47, at each occurrence, is independently selected from H and C1-4 alkyl;
k is 1 or 2;
m is 0, 1, or 2; and
n is 0, 1, 2, or 3.
-
-
3. A compound of claim 2 wherein:
-
X is —
CHR10—
;
R1 is selected from H, C(═
O)R2,C(═
O)OR2,C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-2 R2, C2-4 alkenyl substituted with 0-2 R2, and C2-4 alkynyl substituted with 0-2 R2;
R2, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is selected independently from H, —
OH, —
NR46R47, —
CF3, C1-3 alkyl, and C1-3 alkoxy;
R6b is H;
R7 and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47,C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, and NR14S(O)2R12;
R8 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2,C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH,C1-6 alkyl substituted with 0-1 R10B, C2-6 alkenyl substituted with 0-1 R10B, C2-6 alkynyl substituted with 0-1 R10B, and C1-6 alkoxy;
R10B is selected from C1-4 alkoxy, C3-6 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, phenyl substituted with 0-3 R33, 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 R44;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2, C1-6 alkyl,C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, and NR14S(O)2R12;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R15, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
R16, at each occurrence, is independently selected from H, OH, F, Cl, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, SO2R45, NR46R47, and C1-4 alkyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-4 alkyl;
R47, at each occurrence, is independently selected from H and C1-4 alkyl;
k is 1 or 2;
m is 0 or 1; and
n is 0, 1 or 2.
-
-
4. A compound of claim 2 wherein:
-
X is —
CH2—
;
R1 is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-4 cycloalkyl, C1-3 alkyl substituted with 0-1 R2, C2-3 alkenyl substituted with 0-1 R2, and C2-3 alkynyl substituted with 0-1 R2;
R2, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R42;
C3-6 carbocyclic group substituted with 0-3 R41, 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 R41;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is H, methyl, ethyl, methoxy, —
OH, or —
CF3;
R6b is H;
R7 and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47,C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
R8 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2,C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2,C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R16, at each occurrence, is independently selected from H, OH, F, Cl, CN, NO2, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, methyl, ethyl, and propyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 alkyl;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C1-3 haloalkyl, C3-6 cycloalkyl, and C1-3 alkyl;
R43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R45 is methyl, ethyl, propyl, or butyl;
R46, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R47, at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 0, 1 or 2.
-
-
5. A compound of claim 2 wherein:
-
X is —
CH2—
;
R1 is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-4 cycloalkyl, C1-3 alkyl substituted with 0-1 R2, C2-3 alkenyl substituted with 0-1 R2, and C2-3 alkynyl substituted with 0-1 R2;
R2, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R42;
C3-6 carbocyclic group substituted with 0-3 R41, 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 R41;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is H, methyl, ethyl, methoxy, —
OH, or —
CF3;
R6b is H;
R7 and R9, at each occurrence, are independently selected from H, F, Cl, —
CH3, —
OCH3, —
CF3, —
OCF3, —
CN, and —
NO2,R8 is selected from H, F, Cl, Br, —
CF3, —
OCF3, —
OH, —
CN, —
NO2,C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 0-2 R11, C2-4 alkenyl substituted with 0-2 R11, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2,C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
R12, at each occurrence, is independently selected from C1-4 alkyl substituted with 0-1 R12a, C2-4 alkenyl substituted with 0-1 R12a, C2-4 alkynyl substituted with 0-1 R12a, C3-6 cycloalkyl substituted with 0-3 R33, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R12a, at each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
alternatively, R12 and R13 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 R16;
R14, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R16, at each occurrence, is independently selected from H, OH, F, Cl, CN, NO2, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, methyl, ethyl, and propyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, —
C(═
O)H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy-, C1-4 alkylthio-, C1-4 alkyl-C(═
O)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
O)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-6 alkyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy; and
C2-6 alkenyl substituted with OH, methoxy, ethoxy, propoxy, or butoxy;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 alkyl;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C1-3 haloalkyl, C3-6 cycloalkyl, and C1-3 alkyl;
R43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R45 is methyl, ethyl, propyl, or butyl;
R46, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R47, at each occurrence, is independently selected from from H, methyl, ethyl, propyl, and butyl;
k is 1;
m is 1; and
n is 0, 1 or 2.
-
-
6. A compound of claim 2 wherein:
-
X is —
CH2—
;
R1 is selected from H, C1-5 alkyl substituted with 0-1 R2, C2-5 alkenyl substituted with 0-1 R2, and C2-3 alkynyl substituted with 0-1 R2;
R2 is C3-6 cycloalkyl;
R5 is H, methyl, ethyl, or propyl;
R6a is H, methyl, or ethyl;
R6b is H;
R7 and R9, at each occurrence, are independently selected from H, F, Cl, —
CH3, —
OCH3, —
CF3, —
OCF3, —
CN, and —
NO2,R8 is selected from methyl substituted with R11;
ethenyl substituted with R11;
OR12, SR12, NR12R13, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R11 is selected from phenyl-substituted with 0-5 fluoro;
2-(H3CCH2C(═
O))-phenyl-substituted with R33;
2-(H3CC(═
O))-phenyl-substituted with R33;
2-(HC(═
O))-phenyl-substituted with R33;
2-(H3CCH(OH))-phenyl-substituted with R33;
2-(H3CCH2CH(OH))-phenyl-substituted with R33;
2-(HOCH2)-phenyl-substituted with R33;
2-(HOCH2CH2)-phenyl-substituted with R33;
2-(H3COCH2)-phenyl-substituted with R33;
2-(H3COCH2CH2)-phenyl-substituted with R33;
2-(H3CCH(OMe))-phenyl-substituted with R33;
2-(H3COC(═
O))-phenyl-substituted with R33;
2-(HOCH2CH═
CH)-phenyl-substituted with R33;
2-((MeOC═
O)CH═
CH)-phenyl-substituted with R33;
2-(methyl)-phenyl-substituted with R33;
2-(ethyl)-phenyl-substituted with R33;
2-(i-propyl)-phenyl-substituted with R33;
2-(F3C)-phenyl-substituted with R33;
2-(NC)-phenyl-substituted with R33;
2-(H3CO)-phenyl-substituted with R33;
2-(fluoro)-phenyl-substituted with R33;
2-(chloro)-phenyl-substituted with R33;
3-(NC)-phenyl-substituted with R33;
3-(H3CO)-phenyl-substituted with R33;
3-(fluoro)-phenyl-substituted with R33;
3-(chloro)-phenyl-substituted with R33;
4-(NC)-phenyl-substituted with R33;
4-(fluoro)-phenyl-substituted with R33;
4-(chloro)-phenyl-substituted with R33;
4-(H3CS)-phenyl-substituted with R33;
4-(H3CO)-phenyl-substituted with R33;
4-(ethoxy)-phenyl-substituted with R33;
4-(i-propoxy)-phenyl-substituted with R33;
4-(i-butoxy)-phenyl-substituted with R33;
4-(H3CCH2CH2C(═
O))-phenyl-substituted with R33;
4-((H3C)2CHC(═
O))-phenyl-substituted with R33;
4-(H3CCH2(═
O))-phenyl-substituted with R33;
4-(H3CC(═
O))-phenyl-substituted with R33;
4-(H3CCH2CH2CH(OH))-phenyl-substituted with R33;
4-((H3C)2CHCH(OH))-phenyl-substituted with R33;
4-(H3CCH2CH(OH))-phenyl-substituted with R33;
4-(H3CCH(OH))-phenyl-substituted with R33;
4-(cyclopropyloxy)-phenyl-substituted with R33;
4-(cyclobutyloxy)-phenyl-substituted with R33; and
4-(cyclopentyloxy)-phenyl-substituted with R33;
R12 is selected from phenyl-substituted with 0-5 fluoro;
2-(H3CCH2C(═
O))-phenyl-substituted with R33;
2-(H3CC(═
O))-phenyl-substituted with R33;
2-(HC(═
O))-phenyl-substituted with R33;
2-(H3CCH(OH))-phenyl-substituted with R33;
2-(H3CCH2CH(OH))-phenyl-substituted with R33;
2-(HOCH2)-phenyl-substituted with R33;
2-(HOCH2CH2)-phenyl-substituted with R33;
2-(H3COCH2)-phenyl-substituted with R33;
2-(H3COCH2CH2)-phenyl-substituted with R33;
2-(H3CCH(OMe))-phenyl-substituted with R33;
2-(H3COC(═
O))-phenyl-substituted with R33;
2-(HOCH2CH═
CH)-phenyl-substituted with R33;
2-((MeOC═
O)CH═
CH)-phenyl-substituted with R33;
2-(methyl)-phenyl-substituted with R33;
2-(ethyl)-phenyl-substituted with R33;
2-(i-propyl)-phenyl-substituted with R33;
2-(F3C)-phenyl-substituted with R33;
2-(NC)-phenyl-substituted with R33;
2-(H3CO)-phenyl-substituted with R33;
2-(fluoro)-phenyl-substituted with R33;
2-(chloro)-phenyl-substituted with R33;
3-(NC)-phenyl-substituted with R33;
3-(H3CO)-phenyl-substituted with R33;
3-(fluoro)-phenyl-substituted with R33;
3-(chloro)-phenyl-substituted with R33;
4-(NC)-phenyl-substituted with R33;
4-(fluoro)-phenyl-substituted with R33;
4-(chloro)-phenyl-substituted with R33;
4-(H3CS)-phenyl-substituted with R33;
4-(H3CO)-phenyl-substituted with R33;
4-(ethoxy)-phenyl-substituted with R33;
4-(i-propoxy)-phenyl-substituted with R33;
4-(i-butoxy)-phenyl-substituted with R33;
4-(H3CCH2CH2C(═
O))-phenyl-substituted with R33;
4-((H3C)2CHC(═
O))-phenyl-substituted with R33;
4-(H3CCH2C(═
O))-phenyl-substituted with R33;
4-(H3CC(═
O))-phenyl-substituted with R33;
4-(H3CCH2CH2CH(OH))-phenyl-substituted with R33;
4-((H3C)2CHCH(OH))-phenyl-substituted with R33;
4-(H3CCH2CH(OH))-phenyl-substituted with R33;
4-(H3CCH(OH))-phenyl-substituted with R33;
4-(cyclopropyloxy)-phenyl-substituted with R33;
4-(cyclobutyloxy)-phenyl-substituted with R33; and
4-(cyclopentyloxy)-phenyl-substituted with R33;
R13 is H, methyl, or ethyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring selected from pyrrolyl, pyrrolidinyl, imidazolyl, piperidinyl, piperizinyl, methylpiperizinyl, and morpholinyl;
alternatively, R12 and R13 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 R16;
R15 is H, methyl, ethyl, propyl, or butyl;
R16, at each occurrence, is independently selected from H, OH, F, Cl, CN, NO2, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, and trifluoromethoxy;
R33, at each occurrence, is independently selected from H, F, Cl, —
CH3, —
OCH3, —
CF3, —
OCF3, —
CN, and —
NO2;
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 —
CH2—
, —
CH(OH)—
, or —
C(═
O)—
;
R1 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, 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-CO2—
, propyl-CO2—
, t-butyl-CO2—
, 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═
CH2, —
CH2—
CH═
CH2, —
CH═
CH—
CH3, —
CH≡
CH, —
CH≡
C—
CH3, and —
CH2—
C≡
CH;
R7, R8, and R9, 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)—
,methylCO2—
, ethylCO2—
, propylylCO2—
, isopropylCO2—
, butylCO2—
, phenylCO2—
,dimethylamino-S(═
O)—
, diethylamino-S(═
O)—
, dipropylamino-S(═
O)—
, di-isopropylamino-S(═
O)—
, dibutylamino-S(═
O)—
, diphenylamino-S(═
O)—
,dimethylamino-SO2—
, diethylamino-SO2—
, dipropylamino-SO2—
, di-isopropylamino-SO2—
, dibutylamino-SO2—
, diphenylamino-SO2—
,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-trimethyphenyl, 2,4,6-tritrifluoromethylphenyl, 2,4,6-trimethoxyphenyl, 2,4,6-tritrifluoromethoxyphenyl, 2-chloro-4-CF3-phenyl, 2-fluoro-3-chloro-phenyl, 2-chloro-4-CF3-phenyl, 2-chloro-4-methoxy-phenyl, 2-methoxy-4-isopropyl-phenyl, 2-CF3-4-methoxy-phenyl, 2-methyl-4-methoxy-5-fluoro-phenyl, 2-methyl-4-methoxy-phenyl, 2-chloro-4-CF3O-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-NO2-phenyl, 2-NO2-phenyl, 2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl, 2-Cl-6-F-phenyl, 2-Cl-4-(CHF2)O-phenyl, 2,4-diMeO-6-F-phenyl, 2-CF3-6-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-CF3-4-EtO-phenyl, 2-CF3-4-iPrO-phenyl, 2-CF3-4-Cl-phenyl, 2-CF3-4-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-CH2(OH)-4-MeO-phenyl, 2-CH2(OMe)-4-MeO-phenyl, 2-CH(OH)Et-4-MeO-phenyl, 2-C(═
O)Et-4-MeO-phenyl, (Z)-2-CH═
CHCO2Me-4-MeO-phenyl, 2-CH2CH2CO2Me-4-MeO-phenyl, (Z)-2-CH═
CHCH2(OH)-4-MeO-phenyl, (E)-2-CH═
CHCO2Me-4-MeO-phenyl, (E)-2-CH═
CHCH2(OH)-4-MeO-phenyl, 2-CH2CH2OMe-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—
, —
CH2CH═
CH2, phenyl-CH═
CH—
, (2-Me-4-MeO-phenyl)-CH═
CH—
, cyclohexyl, cyclopentyl, cyclohexylmethyl, —
CH2CH2CO2Et, —
(CH2)3CO2Et, —
(CH2)4CO2Et, benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl, 3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl, 2-OH-benzyl, 2-CO2Me-3-MeO-phenyl, 2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF3-4-CN-phenyl, 3-CHO-phenyl, 3-CH2(OH)-phenyl, 3-CH2(OMe)-phenyl, 3-CH2(NMe2)-phenyl, 3-CN-4-F-phenyl, 3-CONH2-4-F-phenyl, 2-CH2(NH2)-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—
, —
NMe2, 1-pyrrolidinyl, and —
N(tosylate)2,provided that two of R7, R8, and R9, are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
m is 1; and
n is 0, 1 or 2.
-
-
8. A compound of claim 7 of Formula (V)
wherein: -
b is a single bond, wherein the bridge hydrogens are in a cis position;
R1 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═
CH2, —
CH2—
CH═
CH2, —
CH═
CH—
CH3, —
C≡
CH, —
C≡
C—
CH3, and —
CH2—
C≡
CH;
R7 and R9, at each occurrence, are independently selected from hydrogen, fluoro, methyl, trifluoromethyl, and methoxy;
R8 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)—
,methylCO2—
, ethylCO2—
, propylCO2—
, isopropylCO2—
, butylCO2—
, phenylCO2—
,dimethylamino-S(═
O)—
, diethylamino-S(═
O)—
, dipropylamino-S(═
O)—
, di-isopropylamino-S(═
O)—
, dibutylamino-S(═
O)—
, diphenylamino-S(═
O)—
,dimethylamino-SO2—
, diethylamino-SO2—
, dipropylamino-SO2—
, di-isopropylamino-SO2—
, dibutylamino-SO2—
, diphenylamino-SO2—
,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-trimethyphenyl, 2,4,6-tritrifluoromethylphenyl, 2,4,6-trimethoxyphenyl, 2,4,6-tritrifluoromethoxyphenyl, 2-chloro-4-CF3-phenyl, 2-fluoro-3-chloro-phenyl, 2-chloro-4-CF3-phenyl, 2-chloro-4-methoxy-phenyl, 2-methoxy-4-isopropyl-phenyl, 2-CF3-4-methoxy-phenyl, 2-methyl-4-methoxy-5-fluoro-phenyl, 2-methyl-4-methoxy-phenyl, 2-chloro-4-CF3O-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-NO2-phenyl, 2-NO2-phenyl, 2-Cl-3-Me-phenyl, 2-Me-4-EtO-phenyl, 2-Me-4-F-phenyl, 2-Cl-6-F-phenyl, 2-Cl-4-(CHF2)O-phenyl, 2,4-diMeO-6-F-phenyl, 2-CF3-6-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-CF3-4-EtO-phenyl, 2-CF3-4-iPrO-phenyl, 2-CF3-4-Cl-phenyl, 2-CF3-4-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-CH2(OH)-4-MeO-phenyl, 2-CH2(OMe)-4-MeO-phenyl, 2-CH(OH)Et-4-MeO-phenyl, 2-C(═
O)Et-4-MeO-phenyl, (Z)-2-CH═
CHCO2Me-4-MeO-phenyl, 2-CH2CH2CO2Me-4-MeO-phenyl, (Z)-2-CH═
CHCH2(OH)-4-MeO-phenyl, (E)-2-CH═
CHCO2Me-4-MeO-phenyl, (E)-2-CH═
CHCH2(OH)-4-MeO-phenyl, 2-CH2CH2OMe-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—
, —
CH2CH═
CH2, phenyl-CH═
CH—
, (2-Me-4-MeO-phenyl)-CH═
CH—
, cyclohexyl, cyclopentyl, cyclohexylmethyl, —
CH2CH2CO2Et, —
(CH2)3CO2Et, —
(CH2)4CO2Et, benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl, 3-MeO-benzyl, 3-OH-benzyl, 2-MeO-benzyl, 2-OH-benzyl, 2-CO2Me-3-MeO-phenyl, 2-Me-4-CN-phenyl, 2-Me-3-CN-phenyl, 2-CF3-4-CN-phenyl, 3-CHO-phenyl, 3-CH2(OH)-phenyl, 3-CH2(OMe)-phenyl, 3-CH2(NMe2)-phenyl, 3-CN-4-F-phenyl, 3-CONH2-4-F-phenyl, 2-CH2(NH2)-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—
, —
NMe2, 1-pyrrolidinyl, and —
N(tosylate)2; and
is 0, 1 or 2.
-
-
9. A compound of claim 1 wherein:
-
X is —
CHR10—
or —
C(═
O)—
;
R1 is selected from C1-6 alkyl substituted with Z, C2-6 alkenyl substituted with Z, C2-6 alkynyl substituted with Z, C3-6 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;
C1-6 alkyl substituted with 0-2 R2, C2-6 alkenyl substituted with 0-2 R2, C2-6 alkynyl substituted with 0-2 R2, aryl substituted with 0-2 R2, 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 R2;
Z is selected from H, —
CH(OH)R2,—
C(ethylenedioxy)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O) NR2R3,—
NR3C(O)R2,—
C(O)OR2,—
OC(O)R2,—
CH(═
NR4)NR2R3,—
NHC(═
NR4)NR2R3,—
S(O)R2,—
S(O)2R2,—
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, aryl substituted withi 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R3, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkoxy;
alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R4)—
;
R4, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is selected from H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, andaryl substituted with 0-3 R44;
R6b is H;
R7, R8, and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
CN, —
NO2, —
NR46R47,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, (C1-4 haloalkyl)oxy, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH,C1-6 alkyl substituted with 0-1 R10B, C2-6 alkenyl substituted with 0-1 R10B, C2-6 alkynyl substituted with 0-1 R10B, and C1-6 alkoxy;
R10B is selected from C1-4 alkoxy, C3-6 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, phenyl substituted with 0-3 R33, 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 R44;
R11 is selected from H, halo, —
CF3, —
CN, —
NO2,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, OC(O)OR12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)NR12R13, S(O)2NR12R13, NR14S(O)R12, and NR14S(O)2R12;
R12, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
R14, at each occurrence, is independently selected from H and C1-4 alkyl;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, SO2R45, NR46R47, methyl, ethyl, and propyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, SO2R45, NR46R47, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-5 cycloalkyl, C1-3 haloalkyl, C1-3 haloalkyl-oxy-, C1-3 alkyloxy-, C1-3 alkylthio-, C1-3 alkyl-C(═
O)—
, and C1-3 alkyl-C(═
O)NH—
;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, ═
O,C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, SR45, NR46R47, OR48, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-4 alkyl;
R47, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
SO2(C1-4 alkyl), —
SO2(phenyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
R48, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
k is 1 or 2;
m is 0, 1, or 2; and
n is 0, 1 or 2.
-
-
10. A compound of claim 9 wherein:
-
X is —
CHR10—
or —
C(═
O)—
;
R1 is selected from C2-5 alkyl substituted with Z, C2-5 alkenyl substituted with Z, C2-5 alkynyl substituted with Z, C3-6 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;
C1-5 alkyl substituted with 0-2 R2, C2-5 alkenyl substituted with 0-2 R2, and C2-5 alkynyl substituted with 0-2 R2;
Z is selected from H, —
CH(OH)R2,—
C(ethylenedioxy)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O)NR2R3,—
NR3C(O)R2,—
C(O)OR2,—
OC(O)R2,—
CH(═
NR4)NR2R3,—
NHC(═
NR4)NR2R3,—
S(O)R2,—
S(O)2R2,—
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, aryl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R3, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkoxy;
alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R4)—
;
R4, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R5 is H, methyl, or ethyl;
R6a is selected from H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, and C3-6 cycloalkyl;
R6b is H;
R7, R8, and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
OCH3, —
CN, —
NO2, —
NR46R47,C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, (C1-4 haloalkyl)oxy, C1-4 alkyl substituted with 0-2 R11, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)2NR12R13, NR14S(O)2R12, NR14S(O)R12, NR14S(O)2R12, NR12C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R10 is selected from H, —
OH, C1-6 alkyl, C1-4 alkoxy, and C1-2 alkyl substituted with 0-1 R10B;
R10B is C3-6 cycloalkyl or phenyl substituted with 0-3 R33;
R11 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
OCH3, —
CN, —
NO2, —
NR46R47,C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, (C1-4 haloalkyl)oxy, C3-10 carbocyclic group substituted with 0-3 R33, aryl substituted with 0-5 R33, 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 R31;
OR12, SR12, NR12R13, C(O)H, C(O)R12, C(O)NR12R13, NR14C(O)R12, C(O)OR12, OC(O)R12, CH(═
NR14)NR12R13, NHC(═
NR14)NR12R13, S(O)R12, S(O)2R12, S(O)2NR12R13, and NR14S(O)2R12;
R12, at each occurrence, is independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, 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 R31;
R13, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
alternatively, R12 and R13 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R14)—
;
R14, at each occurrence, is independently selected from H and C1-4 alkyl;
R31, at each occurrence, is independently selected from H, OH, halo, CF3, methyl, and ethyl;
R33, at each occurrence, is independently selected from H, OH, halo, CN, NO2, CF3, methyl, and ethyl;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, ═
O,C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, SR45, NR46R47, OR48, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is C3-6 cycloalkyl or aryl substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, C1-4 alkyl, and C1-4 alkoxy;
R45 is C1-4 alkyl;
R46, at each occurrence, is independently selected from H and C1-3 alkyl;
R47, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
SO2(C1-4 alkyl), —
SO2(phenyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
R48, at each occurrence, is independently selected from H, C1-4 alkyl, —
C(═
O)NH(C1-4 alkyl), —
C(═
O)O(C1-4 alkyl), —
C(═
O)(C1-4 alkyl), and —
C(═
O)H;
k is 1 or 2;
m is 0, 1, 2; and
n is 0, 1 or 2.
-
-
11. A compound of claim 9 wherein:
-
X is —
CH2—
;
R1 is selected from C2-4 alkyl substituted with Z, C2-4 alkenyl substituted with Z, C2-4 alkynyl substituted with Z, C3-6 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;
C2-4 alkyl substituted with 0-2 R2, and C2-4 alkenyl substituted with 0-2 R2;
Z is selected from H, —
CH(OH)R2,—
C(ethylenedioxy)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O)NR2R3,—
NR3C(O)R2,—
C(O)OR2,—
S(O)R2,—
S(O)2R2,—
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from phenyl substituted with 0-5 R42;
C3-10 carbocyclic group substituted with 0-3 R41, 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 R41;
R3, at each occurrence, is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkoxy;
alternatively, R2 and R3 join to form a 5- or 6-membered ring optionally substituted with —
O—
or —
N(R4)—
;
R4, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R5 is H;
R6a is selected from H, —
OH, —
CF3, methyl, ethyl, propyl, butyl, methoxy, and, ethoxy;
R6b is H;
R7, R8, and R9, at each occurrence, are independently selected from H, halo, —
CF3, —
OCF3, —
OH, —
OCH3, —
CN, —
NO2,C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, (C1-3 haloalkyl)oxy, and C1-4 alkyl substituted with 0-2 R11;
R11 is selected from H, halo, —
CF3, —
OCF3, —
OH, —
OCH3, —
CN, —
NO2,C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and (C1-3 haloalkyl)oxy;
R33, at each occurrence, is independently selected from H, OH, halo, CF3, and methyl;
R41, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, NR46R47, NO2, CN, ═
O,C2-8 alkenyl, C2-8 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R42, 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 R44;
R42, at each occurrence, is independently selected from H, CF3, halo, OH, CO2H, SO2R45, SR45, NR46R47, OR48, NO2, CN, CH(═
NH)NH2, NHC(═
NH)NH2,C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl substituted with 0-1 R43, aryl substituted with 0-3 R44, 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 R44;
R43 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or pyridyl, each substituted with 0-3 R44;
R44, at each occurrence, is independently selected from H, halo, —
OH, NR46R47, CO2H, SO2R45, —
CF3, —
OCF3, —
CN, —
NO2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, and butoxy;
R45 is methyl, ethyl, propyl, or butyl;
R46, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R47, 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), —
SO2(methyl), —
SO2(ethyl), —
SO2(phenyl), —
C(═
O)O(methyl),—
C(═
O)O(ethyl), —
C(═
O)(methyl), —
C(═
O)(ethyl), and —
C(═
O)H;
R48, 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 0, 1 or 2.
-
-
12. A compound of claim 9 wherein:
-
X is —
CH2—
;
R1 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 R2, propyl substituted with R2, butyl substituted with R2, propenyl substituted with R2, and butenyl substituted with R2;
Z is selected from H, —
CH(OH)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O)NR2R3,—
NR3C(O)R2,—
C(O)OR2,—
S(O)R2,—
S(O)2R2,—
S(O)2NR2R3, and —
NR3S(O)2R2;
R2, at each occurrence, is independently selected from phenyl substituted with 0-3 R42;
naphthyl substituted with 0-3 R42;
cyclopropyl substituted with 0-3 R41;
cyclobutyl substituted with 0-3 R41;
cyclopentyl substituted with 0-3 R41;
cyclohexyl substituted with 0-3 R41;
pyridyl substituted with 0-3 R41;
indolyl substituted with 0-3 R41;
indolinyl substituted with 0-3 R41;
benzimidazolyl substituted with 0-3 R41;
benzotriazolyl substituted with 0-3 R41;
benzothienyl substituted with 0-3 R41;
benzofuranyl substituted with 0-3 R41;
phthalimid-1-yl substituted with 0-3 R41;
inden-2-yl substituted with 0-3 R41;
2,3-dihydro-1H-inden-2-yl substituted with 0-3 R41;
indazolyl substituted with 0-3 R41;
tetrahydroquinolinyl substituted with 0-3 R41; and
tetrahydro-isoquinolinyl substituted with 0-3 R41;
R3, at each occurrence, is independently selected from H, methyl, and ethyl;
R5 is H;
R6a is selected from H, —
OH, methyl, and methoxy;
R6b is H;
R7, R8, and R9, at each occurrence, are independently selected from H, F, Cl, methyl, ethyl, methoxy, —
CF3, and —
OCF3;
R41, at each occurrence, is independently selected from H, F, Cl, Br, OH, CF3, NO2, CN, ═
O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R42, at each occurrence, is independently selected from H, F, Cl, Br, OH, CF3, SO2R45, SR45, NR46R47, OR48, NO2, CN, ═
O, methyl, ethyl, propyl, butyl, methoxy, and ethoxy;
R45 is methyl, ethyl, propyl, or butyl;
R46, at each occurrence, is independently selected from H, methyl, ethyl, propyl, and butyl;
R47, 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), —
SO2(methyl), —
SO2(ethyl), —
SO2(phenyl), —
C(═
O)O(methyl),—
C(═
O)O(ethyl), —
C(═
O)(methyl), —
C(═
O)(ethyl), and —
C(═
O)H;
R48, 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 0, 1 or 2.
-
-
13. A compound of claim 9 of Formula (I-a)
wherein: -
b is a single bond;
X is —
CH2—
, CH(OH)—
, or —
C(═
O)—R1 is selected from —
(CH2)3C(═
O)(4-fluoro-phenyl),—
(CH2)3C(═
O)(4-bromo-phenyl),—
(CH2)3C(═
O)(4-methyl-phenyl),—
(CH2)3C(═
O)(4-methoxy-phenyl),—
(CH2)3C(═
O)(4-(3,4-dichloro-phenyl)phenyl),—
(CH2)3C(═
O)(3-methyl-4-fluoro-phenyl),—
(CH2)3C(═
O)(2,3-dimethoxy-phenyl),—
(CH2)3C(═
O)(phenyl),—
(CH2)3C(═
O)(4-chloro-phenyl),—
(CH2)3C(═
O)(3-methyl-phenyl),—
(CH2)3C(═
O)(4-t-butyl-phenyl),—
(CH2)3C(═
O)(3,4-difluoro-phenyl),—
(CH2)3C(═
O)(2-methoxy-5-fluoro-phenyl),—
(CH2)3C(═
O)(4-fluoro-1-naphthyl),—
(CH2)3C(═
O)(benzyl),—
(CH2)3C(═
O)(4-pyridyl),—
(CH2)3C(═
O)(3-pyridyl),—
(CH2)3CH(OH)(4-fluoro-phenyl),—
(CH2)3CH(OH)(4-pyridyl),—
(CH2)3CH(OH)(2,3-dimethoxy-phenyl),—
(CH2)3S(3-fluoro-phenyl),—
(CH2)3S(4-fluoro-phenyl),—
(CH2)3S(═
O)(4-fluoro-phenyl),—
(CH2)3SO2(3-fluoro-phenyl),—
(CH2)3SO2(4-fluoro-phenyl),—
(CH2)3O(4-fluoro-phenyl),—
(CH2)3O(phenyl),—
(CH2)3O(3-pyridyl),—
(CH2)3O(4-pyridyl),—
(CH2)3O(2-NH2-phenyl),—
(CH2)3O(2-NH2-5-F-phenyl),—
(CH2)3O(2-NH2-4-F-phenyl),—
(CH2)3O(2-NH2-3-F-phenyl),—
(CH2)3O(2-NH2-4-Cl-phenyl),—
(CH2)3O(2-NH2-4-OH-phenyl),—
(CH2)3O(2-NH2-4-Br-phenyl),—
(CH2)3O(2-NHC(═
O)Me-4-F-phenyl),—
(CH2)3O(2-NHC(═
O)Me-phenyl),—
(CH2)3NH(4-fluoro-phenyl),—
(CH2)3N(methyl)(4-fluoro-phenyl),—
(CH2)3CO2(ethyl),—
(CH2)3C(═
O)N(methyl)(methoxy),—
(CH2)3C(═
O)NH(4-fluoro-phenyl),—
(CH2)2NHC(═
O)(phenyl),—
(CH2)2NMeC(═
O)(phenyl),—
(CH2)2NHC(═
O)(2-fluoro-phenyl),—
(CH2)2NMeC(═
O)(2-fluoro-phenyl),—
(CH2)2NHC(═
O)(4-fluoro-phenyl),—
(CH2)2NMeC(═
O)(4-fluoro-phenyl),—
(CH2)2NHC(═
O)(2,4-difluoro-phenyl),—
(CH2)2NMeC(═
O)(2,4-difluoro-phenyl),—
(CH2)3(3-indolyl),—
(CH2)3(1-methyl-3-indolyl),—
(CH2)3(1-indolyl),—
(CH2)3(1-indolinyl),—
(CH2)3(1-benzimidazolyl),—
(CH2)3(1H-1,2,3-benzotriazol-1-yl),—
(CH2)3(1H-1,2,3-benzotriazol-2-yl),—
(CH2)2(1H-1,2,3-benzotriazol-1-yl),—
(CH2)2(1H-1,2,3-benzotriazol-2-yl),—
(CH2)3(3,4 dihydro-1(2H)-quinolinyl),—
(CH2)2C(═
O)(4-fluoro-phenyl),—
(CH2)2C(═
O)NH(4-fluoro-phenyl),—
CH2CH2(3-indolyl),—
CH2CH2(1-phthalimidyl),—
(CH2)4C(═
O)N(methyl)(methoxy),—
(CH2)4CO2(ethyl),—
(CH2)4C(═
O)(phenyl),—
(CH2)4(cyclohexyl),—
(CH2)3CH(phenyl)2,—
CH2CH2CH═
C(phenyl)2,—
CH2CH2CH═
CMe(4-F-phenyl),—
(CH2)3CH(4-fluoro-phenyl)2,—
CH2CH2CH═
C(4-fluoro-phenyl)2,—
(CH2)2(2,3-dihydro-1H-inden-2-yl),—
(CH2)3C(═
O)(2-NH2-phenyl),—
(CH2)3C(═
O)(2-NH2-5-F-phenyl),—
(CH2)3C(═
O)(2-NH2-4-F-phenyl),—
(CH2)3C(═
O)(2-NH2-3-F-phenyl),—
(CH2)3C(═
O)(2-NH2-4-Cl-phenyl),—
(CH2)3C(═
O)(2-NH2-4-OH-phenyl),—
(CH2)3C(═
O)(2-NH2-4-Br-phenyl),—
(CH2)3(1H-indazol-3-yl),—
(CH2)3(5-F-1H-indazol-3-yl),—
(CH2)3(7-F-1H-indazol-3-yl),—
(CH2)3(6-Cl-1H-indazol-3-yl),—
(CH2)3(6-Br-1H-indazol-3-yl),—
(CH2)3C(═
O)(2-NHMe-phenyl),—
(CH2)3(1-benzothien-3-yl),—
(CH2)3(6-F-1H-indol-1-yl),—
(CH2)3(5-F-1H-indol-1-yl),—
(CH2)3(6-F-2,3-dihydro-1H-indol-1-yl),—
(CH2)3(5-F-2,3-dihydro-1H-indol-1-yl),—
(CH2)3(6-F-1H-indol-3-yl),—
(CH2)3(5-F-1H-indol-3-yl),—
(CH2)3(5-F-1H-indol-3-yl),—
(CH2)3(9H-purin-9-yl),—
(CH2)3(7H-purin-7-yl),—
(CH2)3(6-F-1H-indazol-3-yl),—
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)Me-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)Me-phenyl),—
(CH2)3C(═
O)(2-NHCO2Et-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)NHEt-4-F-phenyl),—
(CH2)3C(═
O)(2-NHCHO-4-F-phenyl),—
(CH2)3C(═
O)(2-OH-4-F-phenyl),—
(CH2)3C(═
O)(2-MeS-4-F-phenyl),—
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl),—
(CH2)2C(Me)CO2Me,—
(CH2)2C(Me)CH(OH)(4-F-phenyl)2,—
(CH2)2C(Me)CH(OH)(4-Cl-phenyl)2,—
(CH2)2C(Me)C(═
O)(4-F-phenyl),—
(CH2)2C(Me)C(═
O)(2-MeO-4-F-phenyl),—
(CH2)2C(Me)C(═
O)(3-Me-4-F-phenyl),—
(CH2)2C(Me)C(═
O)(2-Me-phenyl),—
(CH2)2C(Me)C(═
O)phenyl,R7, R8, and R9, 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 R7, R8, and R9, are independently selected from hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, nitro, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy;
k is 1 or 2;
m is 1 or 2; and
n is 0, 1 or 2.
-
-
14. A compound of claim 13 of Formula (V-a)
wherein: -
b is a single bond, wherein the bridge hydrogens are in a cis position;
R1 is selected from —
(CH2)3C(═
O)(4-fluoro-phenyl),—
(CH2)3C(═
O)(4-bromo-phenyl),—
(CH2)3C(═
O)(4-methyl-phenyl),—
(CH2)3C(═
O)(4-methoxy-phenyl),—
(CH2)3C(═
O)(4-(3,4-dichloro-phenyl)phenyl),—
(CH2)3C(═
O)(3-methyl-4-fluoro-phenyl),—
(CH2)3C(═
O)(2,3-dimethoxy-phenyl),—
(CH2)3C(═
O)(phenyl),—
(CH2)3C(═
O)(4-chloro-phenyl),—
(CH2)3C(═
O)(3-methyl-phenyl),—
(CH2)3C(═
O)(4-t-butyl-phenyl),—
(CH2)3C(═
O)(3,4-difluoro-phenyl),—
(CH2)3C(═
O)(2-methoxy-5-fluoro-phenyl),—
(CH2)3C(═
O)(4-fluoro-1-naphthyl),—
(CH2)3C(═
O)(benzyl),—
(CH2)3C(═
O)(4-pyridyl),—
(CH2)3C(═
O)(3-pyridyl),—
(CH2)3CH(OH)(4-fluoro-phenyl),—
(CH2)3CH(OH)(4-pyridyl),—
(CH2)3CH(OH)(2,3-dimethoxy-phenyl),—
(CH2)3S(3-fluoro-phenyl),—
(CH2)3S(4-fluoro-phenyl),—
(CH2)3S(═
O)(4-fluoro-phenyl),—
(CH2)3SO2(3-fluoro-phenyl),—
(CH2)3SO2(4-fluoro-phenyl),—
(CH2)3O(4-fluoro-phenyl),—
(CH2)3O(phenyl),—
(CH2)3NH(4-fluoro-phenyl),—
(CH2)3N(methyl)(4-fluoro-phenyl),—
(CH2)3CO2(ethyl),—
(CH2)3C(═
O)N(methyl)(methoxy),—
(CH2)3C(═
O)NH(4-fluoro-phenyl),—
(CH2)2NHC(═
O)(phenyl),—
(CH2)2NMeC(═
O)(phenyl),—
(CH2)2NHC(═
O)(2-fluoro-phenyl),—
(CH2)2NMeC(═
O)(2-fluoro-phenyl),—
(CH2)2NHC(═
O)(4-fluoro-phenyl),—
(CH2)2NMeC(═
O)(4-fluoro-phenyl),—
(CH2)2NHC(═
O)(2,4-difluoro-phenyl),—
(CH2)2NMeC(═
O)(2,4-difluoro-phenyl),—
(CH2)3(3-indolyl),—
(CH2)3(1-methyl-3-indolyl),—
(CH2)3(1-indolyl),—
(CH2)3(1-indolinyl),—
(CH2)3(1-benzimidazolyl),—
(CH2)3(1H-1,2,3-benzotriazol-1-yl),—
(CH2)3(1H-1,2,3-benzotriazol-2-yl),—
(CH2)2(1H-1,2,3-benzotriazol-1-yl),—
(CH2)2(1H-1,2,3-benzotriazol-2-yl),—
(CH2)3(3,4 dihydro-1(2H)-quinolinyl),—
(CH2)2C(═
O)(4-fluoro-phenyl),—
(CH2)2C(═
O)NH(4-fluoro-phenyl),—
CH2CH2(3-indolyl),—
CH2CH2(1-phthalimidyl),—
(CH2)4C(═
O)N(methyl)(methoxy),—
(CH2)4CO2(ethyl),—
(CH2)4C(═
O)(phenyl),—
(CH2)4(cyclohexyl),—
(CH2)3CH(phenyl)2,—
CH2CH2CH═
C(phenyl)2,—
CH2CH2CH═
CMe(4-F-phenyl),—
(CH2)3CH(4-fluoro-phenyl)2,—
CH2CH2CH═
C(4-fluoro-phenyl)2,—
(CH2)2(2,3-dihydro-1H-inden-2-yl),—
(CH2)3C(═
O)(2-NH2-phenyl),—
(CH2)3C(═
O)(2-NH2-5-F-phenyl),—
(CH2)3C(═
O)(2-NH2-4-F-phenyl),—
(CH2)3C(═
O)(2-NH2-3-F-phenyl),—
(CH2)3C(═
O)(2-NH2-4-Cl-phenyl),—
(CH2)3C(═
O)(2-NH2-4-OH-phenyl),—
(CH2)3C(═
O)(2-NH2-4-Br-phenyl),—
(CH2)3(1H-indazol-3-yl),—
(CH2)3(5-F-1H-indazol-3-yl),—
(CH2)3(7-F-1H-indazol-3-yl),—
(CH2)3(6-Cl-1H-indazol-3-yl),—
(CH2)3(6-Br-1H-indazol-3-yl),—
(CH2)3C(═
O)(2-NHMe-phenyl),—
(CH2)3(1-benzothien-3-yl),—
(CH2)3(6-F-1H-indol-1-yl),—
(CH2)3(5-F-1H-indol-1-yl),—
(CH2)3(6-F-2,3-dihydro-1H-indol-1-yl),—
(CH2)3(5-F-2,3-dihydro-1H-indol-1-yl),—
(CH2)3(6-F-1H-indol-3-yl),—
(CH2)3(5-F-1H-indol-3-yl),—
(CH2)3(5-F-1H-indol-3-yl),—
(CH2)3(9H-purin-9-yl),—
(CH2)3(7H-purin-7-yl),—
(CH2)3(6-F-1H-indazol-3-yl),—
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)Me-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)Me-4-F-phenyl),—
(CH2)3C(═
O)(2-NHCO2Et-4-F-phenyl),—
(CH2)3C(═
O)(2-NHC(═
O)NHEt-4-F-phenyl),—
(CH2)3C(═
O)(2-NHCHO-4-F-phenyl),—
(CH2)3C(═
O)(2-OH-4-F-phenyl),—
(CH2)3C(═
O)(2-MeS-4-F-phenyl),—
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl),—
(CH2)2C(Me)CO2Me,—
(CH2)2C(Me)CH(OH)(4-F-phenyl)2,—
(CH2)2C(Me)CH(OH)(4-Cl-phenyl)2,—
(CH2)2C(Me)C(═
O)(4-F-phenyl),—
(CH2)2C(Me)C(═
O)(2-MeO-4-F-phenyl),—
(CH2)2C(Me)C(═
O)(3-Me-4-F-phenyl),—
(CH2)2C(Me)C(═
O)(2-Me-phenyl),—
(CH2)2C(Me)C(═
O)phenyl,R7, R8, and R9, 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, methylC(═
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 R7, R8, and R9, are independently selected from hydrogen, fluoro, chloro, methyl, trifluoromethyl, methoxy, and trifluoromethoxy;
m is 1 or 2; and
n is 0, 1 or 2.
-
-
15. A compound of claim 1 selected from the group consisting of
(± - )-cis-9-(cyclopropylcarbonyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-9-isobutyryl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (±
)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(3,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(2,3-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(5-isopropyl-2-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(3-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
tert-butyl (±
)-cis-2-(2,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(±
)-cis-2-(2-chlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(2,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(3,4-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(2,3-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(4-isopropyl-2-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(3-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
(±
)-cis-2-(2,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (±
)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl (±
)-cis-2-bromo-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl (±
)-cis-2-(2,3-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl (±
)-cis-2-(3,4-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
tert-butyl (±
)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
(±
)-cis-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(±
)-cis-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(±
)-cis-2-[2-chloro-4-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
4((±
)-cis-2-(2-chlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±
)-cis-2-(2,4-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±
)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]qionolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±
)-cis-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-9(6aH)-yl)-1-(4-fluorophenyl)-1-butanone;
(6aS,10aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido [4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(4-chloro-2-fluorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-phenyl-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-phenyl-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3,4-dimethoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3,5-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-isopropyl-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(5-fluoro-4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(4-methoxy-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
tert-butyl (6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate;
(6aS,10aR)-2-(3-chloro-2-methylphenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]-2-yl]-5-methoxybenzaldehyde;
(6aS,10aR)-2-(2,6-dichlorophenyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
N-[4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenyl]-N-methylamine;
4-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-3-(trifluoromethyl)phenylamine;
1-(2-[(6aS,10aR)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indol-2-yl]-5-methoxyphenyl)ethanol;
tert-butyl (±
)-cis-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
tert-butyl (8aS,12aR)-2-bromo-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
(8aS,12aR)-2-(2,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,3-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,4-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,5-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,6-dichlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(4-chlorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(±
)-cis-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,6-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2,3-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3,4-difluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(3-fluorophenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2-chloro-4-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-chloro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-(4-methoxy-2-methylphenyl)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[2,4-bis(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
(8aS,12aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indole;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-(trifluoromethyl)aniline;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-N-methyl-3-(trifluoromethyl)aniline;
2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]benzaldehyde;
{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]phenyl}methanol;
2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxybenzaldehyde;
{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}methanol;
4-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-3-methylbenzonitrile;
1-{2-[(8aS,12aR)-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-2-yl]-5-methoxyphenyl}ethanol;
tert-butyl (7aS,11aR)-2-bromo-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate;
(7aS,11aR)-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,5-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(4-chlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,6-difluorophenyl)-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3,4-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(3-fluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2-chloro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2-fluoro-4-methoxyphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(4-methoxy-2-methylphenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)phenol;
(7aS,11aR)-2-[2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-isopropoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[2,4-bis(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-(trifluoromethyl)aniline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-N-methyl-3-(trifluoromethyl)aniline;
4-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-3-methylbenzonitrile;
2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]benzaldehyde;
{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]phenyl}methanol;
2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxybenzaldehyde;
{2-[(7aS,11aR)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-2-yl]-5-methoxyphenyl}methanol;
(8aS,12aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;
(7aS,11aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(8aS,12aR)-2-[3-chloro-2-methylphenyl]-4,5,6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3b]indole;
(7aS,11aR)-2-[3-chloro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[5-fluoro-2-methylphenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(±
)-cis-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(±
)-cis-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,3-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-(2,4-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-(2,4-dichlorophenyl)-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(cyclobutylmethyl)-2-(2,3-dichlorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-ethyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-propyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-butyl-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(4-pentenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-10-(3-methyl-2-butenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(2-fluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(2,2-difluoroethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-(cyclobutylmethyl)-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-aminophenyl)-1-butanone;
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-aminophenyl)-1-butanone;
(±
)-cis-3-(5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)propyl 4-fluorophenyl ether;
4-((±
)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(4-pyridinyl)-1-butanone;
(±
)-cis-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(7aS,11aR)-10-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline;
(±
)-cis-4-(4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((8aS,12aR)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((8aR,12aS)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(4-fluorophenyl)-1-butanone;
4-((±
)-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-11(8aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone;
4-((±
)-cis-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone4-((7aS,11aR)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone; and
4-((7aR,11aS)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10(7aH)-yl)-1-(2-amino-4-fluorophenyl)-1-butanone.
- )-cis-9-(cyclopropylcarbonyl)-4,5,6a,7,8,9,10,10a-octahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole;
-
16. A compound of claim 1 selected from the group consisting of
4-[(± - )-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′
,5′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(4-fluorophenyl)-1-butanone;
4-[(±
)-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′
,5′
;
4,5]pyrrolo[3,2,1-ij]quinolin-10-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;
4-[(±
)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b;
3,2,1-hi]indol-11-yl]-1-(4-fluorophenyl)-1-butanone;
4-[(±
)-4,5,6,7,9,10,11,12,13,13a-decahydro-11H-diazepino[4,5-b;
3,2,1-hi]indol-11-yl]-1-(2-amino-4-fluorophenyl)-1-butanone;
tert-butyl (±
)-cis-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate;
tert-butyl (±
)-cis-2-bromo-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline-11-carboxylate; and
(±
)-cis-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[3′
,4′
;
4,5]pyrrolo[3,2,1-ij]quinoline.
- )-5,6,8,9,10,11,12,12a-octahydro-4H,7aH-azepino[4′
-
17. A compound of claim 1 selected from the group consisting of
tert-butyl (± - )-cis-2-bromo-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
tert-butyl (±
)-cis-2-(2,4-dichlorophenyl)-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
(±
)-cis-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aS, 12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aR, 12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4(5H)-one;
(8aS, 12aR)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol; and
(8aR, 12aS)-2-(2,4-dichlorophenyl)-6,7,8a,9,10,11,12,12a-decahydroazepino[3,2,1-hi]pyrido[4,3-b]indol-4-ol.
- )-cis-2-bromo-4-oxo-4,5,6,7,9,10,12,12a-octahydroazepino[3,2,1-hi]pyrido[4,3-b]indole-11(8aH)-carboxylate;
-
18. 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, 15, 16, or 17, or a pharmaceutically acceptable salt thereof.
-
19. A method for treating a human suffering from a disorder associated with 5HT2C receptor modulation selected from obesity, anorexia, bulemia, depression, 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.
-
20. 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, 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.
-
21. 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.
-
22. 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.
-
23. A method for treating depression 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.
Specification