Substituted heterocycle fused gamma-carbolines
First Claim
1. A compound of formula (I):
-
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein;
b is a single bond;
X is —
O—
, —
S—
, —
S(═
O)—
, or —
S(═
O)2—
;
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, 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 cycloakyl, 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 R42;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is selected from H;
H, —
OH, —
NR46R47, —
CF3, C1-4 alkyl, C1-4 alkoxy, C3-4 haloalkyl, and aryl substituted with O-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 —
OH, —
CN, —
NO2, C2-8 alkenyl, C2-8 alkynyl, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 1-2 R33, C2-4 alkenyl substituted with 0-2 R13, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted wit 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;
R11 is selected from —
CN, —
NO2, C2-8 alkenyl, C2-8 alkynyl, 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)NR12R13, SO(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;
R32, 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, C2-4 alkenyl, C2-6 alkynyl, C2-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy, C1-4 alkylthio-, C1-4 alkyl-C(═
)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
)—
, C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-4 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 C2-6 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 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.
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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
33 Claims
-
1. A compound of formula (I):
-
or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein; b is a single bond;
X is —
O—
, —
S—
, —
S(═
O)—
, or —
S(═
O)2—
;
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, 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 cycloakyl, 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 R42;
R5 is H, methyl, ethyl, propyl, or butyl;
R6a is selected from H;
H, —
OH, —
NR46R47, —
CF3,C1-4 alkyl, C1-4 alkoxy, C3-4 haloalkyl, and aryl substituted with O-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 —
OH, —
CN, —
NO2,C2-8 alkenyl, C2-8 alkynyl, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 1-2 R33, C2-4 alkenyl substituted with 0-2 R13, C2-4 alkynyl substituted with 0-1 R11, C3-10 carbocyclic group substituted wit 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;
R11 is selected from —
CN, —
NO2,C2-8 alkenyl, C2-8 alkynyl, 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)NR12R13, SO(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;
R32, 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, C2-4 alkenyl, C2-6 alkynyl, C2-6 cycloalkyl, C1-4 haloalkyl, C1-4 haloalkyl-oxy-, C1-4 alkyloxy, C1-4 alkylthio-, C1-4 alkyl-C(═
)—
, C1-4 alkyl-C(═
O)NH—
, C1-4 alkyl-OC(═
)—
,C1-4 alkyl-C(═
O)O—
, C3-6 cycloalkyl-oxy-, C3-6 cycloalkylmethyl-oxy-;
C1-4 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 C2-6 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 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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 21, 22, 24, 31, 32, 33)
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 —
OH, —
CN, —
NO2,C2-4 alkenyl, C2-4 alkynyl, (C1-4 haloalkyl)oxy, C3-10 cycloalkyl substituted with 0-2 R33, C1-4 alkyl substituted with 1-2 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, C(O)R15, NR12C(O)OR15, NR12S(O)2R15, and NR12C(O)NHR15;
R11 is selected from —
CN, —
NO2,C2-4 alkenyl, C2-4 alkynyl, 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, each occurrence, is independently selected from phenyl substituted with 0-5 R33;
C3-10 carbocyclic group substituted with 0-3 R33, and b 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 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, C3-4 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 butyoxy; 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, SO2H, 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 1 or 2.
-
-
8. A compound of claim 1 wherein:
-
X is —
O—
;
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-(HOCH2)-phenyl-substituted with R33;
2-(HOCH3CH2)-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;
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(═
))-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 form 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, and 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.
-
-
9. A compound of claim 2 of Formula
wherein: -
b is a single bond;
X is —
S—
or —
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, 2-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)—
,(3,5-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, —
C═
CH, —
C═
CH—
CH3, and —
CH2C═
—
CH;
R8 is selected from cyano, nitro, trifluoromethoxy, phenyl, methylC(═
)—
, ethylC(═
)—
, 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-ethylpropyl, 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-trifluoromethylphenyl, 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-trichlorohenyl, 2,4,6-trifluorophenyl, 2,4,6-trimethylphenyl, 2,4,6-trifluoromethylphenyl, 2,4,6-trimethoxyphenyl, 2,4,6-trifluoromethoxyphenyl, 2-chloro-4-CF3-phenyl, 2-fluoro-3-chloro-phenyl, 2-chloro-4-CF3-phenyl, 2-chloro-4-methoxy-phenyl, 2-methoxy-4-isopropyl-butyl, 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-4-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-tert-F-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-CHO(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—
, (2,4-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, R7 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;
m is 1; and
n is 1 or 2.
-
-
10. A compound of claim 9 of Formula (II)
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-methylphenyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-propyl, 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,—
CH═
CH2, —
CH2—
CH═
CH2, —
CH═
CH—
CH3, —
C≡
—
CH, —
C≡
—
C—
CH3, and —
CH2—
CH≡
CH;
R7 and R9, at each occurrence, are independently selected from hydrogen, fluoro, methyl, trifluoromethyl, and methoxy;
R8 is selected from cyano, nitro, trifluoromethoxy, phenyl, methylC(═
O)—
, ethylC(═
O)—
, propylC(═
O)—
, isopropylC(═
O)—
, butylC(═
O)—
, phenylC(═
)—
,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-trifluromethylphenyl, 2-methoxyphenyl, 2-trifluoromethoxyphenyl, 3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl, 3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl, 3-propylphenyl, 3-isopropylphenyl, 3-butylphenyl, 3-trifluoromethyl, 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-trifluoromethylphenyl, 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-trichlorohenyl, 2,4,6-trifluorophenyl, 2,4,6-trimethylphenyl, 2,4,6-trifluoromethylphenyl, 2,4,6-trimethoxyphenyl, 2,4,6-trifluoromethoxyphenyl, 2-chloro-4-CF3-phenyl, 2-fluoro-3-chloro-phenyl, 2-chloro-4-CF3-phenyl, 2-chloro-4-methoxy-phenyl, 2-methoxy-4-isopropyl-butyl, 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-4-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-tert-F-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-CHO(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—
, (2,4-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
n is 1 or 2.
-
-
11. A compound of claim 9 of Formula (III)
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-methylphenyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-propyl, 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—
CH≡
CH;
R7 and R9, at each occurrence, are independently selected from hydrogen, fluoro, methyl, trifluoromethyl, and methoxy; and
R8 is selected from cyano, nitro, trifluoromethoxy, phenyl, methylC(═
O)—
, ethylC(═
O)—
, propylC(═
O)—
, isopropylC(═
O)—
, butylC(═
O)—
, phenylC(═
)—
,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-trifluoromethoxyphenyl, 3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,4-ditrifluoromethylphenyl, 3,4-dimethoxyphenyl, 3,4-ditrifluoromethoxyphenyl, 2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl, 2,4,6-trimethylphenyl, 2,4,6-trifluoromethylphenyl, 2,4,6-trimethoxyphenyl, 2,4,6-trifluoromethoxyphenyl, 2-chloro-4-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-5F-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-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-5-Cl-phenyl, 2,3,4-tetraF-phenyl, 2,3,4,5,6-pentaF-phenyl, 2-CF3-4-EtO-phenyl, 2-CF3-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, 2C(═
O)Me-4-MeO-phenyl,2-CH2(OH)-4-O-phenyl, 2-CH3(OMe)-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-CH2C2OMe-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═
C—
,cyclohexyl, cyclopentyl, cyclohexylmethyl, 13 CH2CH2CO2Et, —
(CH2)3CO2Et, —
(CH2)4CO2Et,benzyl, 2-F-benzyl, 3-F-benzyl, 4-F-benzyl, 3-MeO-benyzl, 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—
, —
NM2, 1-pyrrolidinyl, and —
N(tosylate)2; and
n is 1 or 2.
-
-
21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claims 1-20 or a pharmaceutically acceptable salt thereof.
-
22. 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, addictive behavior, obsessive-compulsive disorder, and sexual disorders;
- comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claims 1-11 or a pharmaceutically acceptable salt thereof.
-
24. A method for treating obesity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claims 1-11, or a pharmaceutically acceptable salt thereof.
-
31. A compound of claim 1 selected from the compounds disclosed in Table 1A:
-
TABLE 1A Ex # R7 R8 R9 b R1 125 H H Br sgl —
CO2—
tBu126 H H 2,6-diF-phenyl sgl —
CO2—
tBu128 H 2,4-diCl-phenyl H sgl H 129 H phenyl H sgl H 130 H 4-F-phenyl H sgl H 131 H 4-Cl-phenyl H sgl H 132 H 2-Cl-phenyl H sgl H 133 H 2-MeO-phenyl H sgl H 134 H 2-Cl-4-CF3-phenyl H sgl H 135 H 2,4-diMe-phenyl H sgl H 136 H 2-Cl-4-MeO-phenyl H sgl H 137 H 4-iPr-phenyl H sgl H 138 H 4-Bu-phenyl H sgl H 139 H 2-Me-4-MeO-5-F-phenyl H sgl H 140 H 2-Me-4-MeO-phenyl H sgl H 141 H 2-Cl-4-CF3O-phenyl H sgl H 142 H 2,4,5-triMe-phenyl H sgl H 143 H 3-Cl-phenyl H sgl H 144 H 4-Me-phenyl H sgl H 145 H 2-Me-4-Cl-phenyl H sgl H 146 H 2,5-diCl-phenyl H sgl H 147 H 2-MeO-4-iPr-phenyl H sgl H 148 H 2,6-diCl-phenyl H sgl H 149 H 2,6-diF-phenyl H sgl H 150 H 2-CF3-4-MeO-phenyl H sgl H 151 H 2-CF3-phenyl H sgl H 152 H 4-pyridyl H sgl H 153 H 2-furanyl H sgl H 154 H 2-thiophenyl H sgl H 155 H 4-F-phenyl H sgl H 156 H 2,3-diCl-phenyl H sgl H 157 H 4-Et-phenyl H sgl H 158 H 2,4-diMeO-phenyl H sgl H 159 H 2-F-3-Cl-phenyl H sgl H 160 H 4-MeO-phenyl H sgl H 161 H 4-MeS-phenyl H sgl H 162 H 4-CN-phenyl H sgl H 163 H 3-CF3-phenyl H sgl H 164 H 2-MeO-phenyl H sgl H 165 H 2-naphthyl H sgl H 166 H 4-acetylphenyl H sgl H 167 H 3-acetamidophenyl H sgl H 168 H 2,4-diCl-phenyl H sgl Me 316 H 2,3-diMe-phenyl H sgl H 317 H 2-Me-5-F-phenyl H sgl H 318 H 2-F-5-Me-phenyl H sgl H 319 H 2-MeO-5-F-phenyl H sgl H 320 H 2-Me-3-Cl-phenyl H sgl H 321 H 3-NO2-phenyl H sgl H 322 H 2-NO2-phenyl H sgl H 323 H 2-Cl-3-Me-phenyl H sgl H 324 H 2-MeO-phenyl H sgl H 325 H 2,3-diCl-phenyl H sgl H 326 H 2-Cl-4-CF3-phenyl H sgl H 327 H 2-Me-4-EtO-phenyl H sgl H 328 H 2-Me-4-F-phenyl H sgl H 329 H 4-Bu-phenyl H sgl H 330 H 2-CF3-phenyl H sgl H 331 H 2-Cl-6-F-phenyl H sgl H 332 H 2-Cl-4-(CHF3)O-phenyl H sgl H 333 H 4-CF3-phenyl H sgl H 334 H 4-Me-phenyl H sgl H 335 H 4-CF3O-phenyl H sgl H 336 H 2,4-diMeO-6-F-phenyl H sgl H 337 H 2-Me-phenyl H sgl H 338 H 2-CF3-6-F-phenyl H sgl H 339 H 2-MeS-phenyl H sgl H 340 H 2,4,6-triF-phenyl H sgl H 341 H 2,4,6-triCl-phenyl H sgl H 342 H 2,6-diCl-4-MeO-phenyl H sgl H 343 H 2,3,4-triF-phenyl H sgl H 344 H 2,6-diF-4-Cl-phenyl H sgl H 345 H 2,3,4,6-tetraF-phenyl H sgl H 346 H 2,3,4,5,6-pentaF-phenyl H sgl H 347 H 2,6-diCF3-phenyl H sgl H 348 H 2-CF3O-phenyl H sgl H 349 H 2-CF3-4-EtO-phenyl H sgl H 350 H 2-CF3-4-iPrO-phenyl H sgl H 351 H 2-naphtyl H sgl H 352 H 2-CF3-4-Cl-phenyl H sgl H 353 H 2-CF3-4-F-phenyl H sgl H 354 H 2,4-diF-phenyl H sgl Me 380 H 2-Cl-4-EtO-phenyl H sgl H 381 H 2-Cl-4-iPrO-phenyl H sgl H 382 H 2-Et-4-MeO-phenyl H sgl H 383 H 2-CHO-4-MeO-phenyl H sgl H 384 H 2-CH(OH)Me-4-MeO-phenyl H sgl H 385 H 2-CH(OMe)Me-4-MeO-phenyl H sgl H 386 H 2-C(═
O)Me-4-MeO-phenylH sgl H 387 H 2-CH2(OH)Me-4-MeO-phenyl H sgl H 388 H 2-CH2(OMe)Me-4-MeO-phenyl H sgl H 389 H 2-CH(OH)Et-4-MeO-phenyl H sgl H 390 H 2-C(═
O)Et-4-MeO-phenylH sgl H 391 H (Z)-2-CH═
CHCO2Me-4-MeO-phenylH sgl H 392 H 2-CH2CH2CO2Me-4-MeO-phenyl H sgl H 393 H (Z)-2-CH═
CHCH2(OH)-4-MeO-phenylH sgl H 394 H (E)-2-CH═
CHCO2Me-4-MeO-phenylH sgl H 395 H (E)-2-CH═
CHCH2(OH)-4-MeO-phenylH sgl H 396 H 2-CH2CH2OMe-4-MeO-phenyl H sgl H 397 H 2-F-4-MeO-phenyl H sgl H 403 H 2-Cl-4-phenyl H sgl H 405 H (2-Cl-phenyl)-CH═
CH—H sgl H 406 H (3-Cl-phenyl)-CH═
CH—H sgl H 407 H (2,6-diF-phenyl)-CH═
CH—H sgl H 410 H cyclohexyl H sgl H 411 H cyclopentyl H sgl H 412 H cyclohexylmethyl H sgl H 413 H —
CH2CH2CO2EtH sgl H 414 H —
(CH2)3CO2EtH sgl H 415 H —
(CH2)4CO2EtH sgl H 416 H —
CH2CH═
CH2H sgl H 417 H Pr H sgl H 418 H benzyl H sgl H 419 H 2-F-benzyl H sgl H 420 H 3-F-benzyl H sgl H 421 H 4-F-benzyl H sgl H 422 H 3-MeO-benzyl H sgl H 423 H 3-OH-benzyl H sgl H 424 H 2-MeO-benzyl H sgl H 425 H 2-OH-benzyl H sgl H 426 H 2-CO2Me-3-MeO-phenyl H sgl H 427 H 2,6-diF-phenyl H sgl H 428 H phenyl-CH═
CH—H sgl H 429 H (2-Me-4-MeO-phenyl)-CH═
CH—H sgl H 430 H —
NMe2H sgl H 431 H 1-pyrrolidinyl H sgl H 432 H —
NTa2H sgl H 433 H MeO H sgl H 445 H 2-Me-4-MeO-phenyl Me sgl H 446 H 2-CF3-4-MeO-phenyl Me sgl H 458 Me 2-CF3-4-MeO-phenyl H sgl H 459 Me 2,4-diCl-phenyl H sgl H 460 H 3-CN-phenyl H sgl H 461 H 2-Me-4-CN-phenyl H sgl H 462 H 2-Me-3-CN-phenyl H sgl H 463 H 2-CN-phenyl H sgl H 464 H 2-CF3-4-CN-phenyl Me sgl H 465 H 3-CHO-phenyl Me sgl H 466 H 3-CH2(OH)-phenyl Me sgl H 467 H 3-CH2(OMe)-phenyl Me sgl H 468 H 3-CH2(NMe2)-phenyl Me sgl H 469 H 3-CN-4-F-phenyl Me sgl H 470 H 3-CONH2-4-F-phenyl Me sgl H 581 H phenyl-NH— H sgl H 583 H (4-F-phenyl)-NH— H sgl H 584 H (2,4-diCl-phenyl)-NH— H sgl H 585 H phenyl-C(═
O)NH—H sgl H 586 H benzyl-NH— H sgl H 587 H phenyl-S— H sgl H 589 H 2-CH2(NH2)4-MeO-phenyl- H sgl H 590 H 2-Me-4-MeO-phenyl- H sgl H 592 H (2-Me-4-MeO-phenyl)-NH— H sgl H 593 H (2-F-4-MeO-phenyl)-NH— H sgl H 595 H (2-Me-4-F-phenyl)-NH— H sgl H 596 H 2-CH(OH)Me-4-F-phenyl H sgl H or pharmaceutically acceptable salt forms thereof.
-
-
32. A compound of claim 1 selected from the compounds closed in Table 2A:
-
TABLE 2A Ex # n k m R7 R8 R9 b R1 479 2 2 1 H 2,4-diCl-phenyl H sgl H 480 2 2 1 H 2-Cl-4-MeO-phenyl H sgl H 481 2 2 1 H 2-Me-4-MeO-phenyl H sgl H 482 2 2 1 H Br H sgl H 497 1 1 1 H 2-Cl-phenyl H sgl H 498 1 1 1 H 3-Cl-phenyl H sgl H 499 1 1 1 H 3-F-phenyl H sgl H 500 1 1 1 H 4-Cl-phenyl H sgl H 501 1 1 1 H 4-F-phenyl H sgl H 502 1 1 1 H 2,3-diCl-phenyl H sgl H 503 1 1 1 H 2,4-diF-phenyl H sgl H 504 1 1 1 H 3,5-diCl-phenyl H sgl H 505 1 1 1 H 3,5-diF-phenyl H sgl H 506 1 1 1 H 3,4-diCl-phenyl H sgl H 507 1 1 1 H 3,4-diF-phenyl H sgl H 508 1 1 1 H 3-Cl-4-F-phenyl H sgl H 509 1 1 1 H 2-F-4-Cl-phenyl H sgl H or pharmaceutically acceptable salt forms thereof.
-
-
33. A compound of claim 1 selected from the compounds disclosed in Table 3A:
-
TABLE 3A Ex # n k m R7 R8 R9 b R1 173 1 1 1 H 2,4-diCl-phenyl H sgl H 174 1 1 1 H 2-Cl-4-MeO-phenyl H sgl H 436 1 1 1 H 2-Cl-phenyl H sgl H 497 1 1 1 H 2-Cl-phenyl H sgl H 498 1 1 1 H 3-Cl-phenyl H sgl H 499 1 1 1 H 3-F-phenyl H sgl H 500 1 1 1 H 4-Cl-phenyl H sgl H 501 1 1 1 H 4-F-phenyl H sgl H 502 1 1 1 H 2,3-diCl-phenyl H sgl H 503 1 1 1 H 2,3-diF-phenyl H sgl H 504 1 1 1 H 3,5-diCl-phenyl H sgl H 505 1 1 1 H 3,5-diF-phenyl H sgl H 506 1 1 1 H 3,4-diCl-phenyl H sgl H 507 1 1 1 H 3,4-diF-phenyl H sgl H 508 1 1 1 H 3-Cl-4-F-phenyl H sgl H 509 1 1 1 H 2-F-4-Cl-phenyl H sgl H 510 1 1 1 H 2-Cl-4-F-phenyl H sgl H 511 1 1 1 H 2,5-diCl-phenyl H sgl H 512 1 1 1 H 2,6-diCl-phenyl H sgl H 513 1 1 1 H 2-CF3-phenyl H sgl H 514 1 1 1 H 4-CF3-phenyl H sgl H 515 1 1 1 H 2,4-diCF3-phenyl H sgl H 516 1 1 1 H 2-Cl-4-CF3-phenyl H sgl H 517 1 1 1 H 2-MeO-phenyl H sgl H 518 1 1 1 H 2,4-diMeO-phenyl H sgl H 519 1 1 1 H 2-MeO-5-iPr-phenyl H sgl H 520 1 1 1 H 3-NO2-phenyl H sgl H 521 1 1 1 H 2-CHO-phenyl H sgl H 522 1 1 1 H 2-CH(Me)(OH)-phenyl H sgl H 523 1 1 1 H 2-CH2(OH)-phenyl H sgl H 524 1 1 1 H 2-CHO-4-MeO-phenyl H sgl H 525 1 1 1 H 2-OH-phenyl H sgl H 526 1 1 1 H 2-CF3-4-EtO-phenyl H sgl H 527 1 1 1 H 2-CF3-4-iPrO-phenyl H sgl H 532 1 1 1 H 2-Me-4-MeO-phenyl H sgl H 533 1 1 1 H 2-CF3-4-MeO-phenyl H sgl H 534 1 2 1 H 3,4,5-triMeo-phenyl H sgl H 535 1 2 1 H 1-naphthyl H sgl H 536 1 2 1 H 3-MeO-phenyl H sgl H 537 1 2 1 H 2,4-diCl-phenyl H sgl H 543 2 1 1 H 2,6-diF-phenyl H sgl H 547 2 1 1 H 2-CF3-4-MeO-phenyl H sgl H 548 2 1 1 H 2-Me-4-MeO-phenyl H sgl H 549 2 1 1 H 2-Cl-4-CF3-phenyl H sgl H 550 2 1 1 H 2,3-diCl-phenyl H sgl H 551 2 1 1 H 2,4-diMeO-phenyl H sgl H 552 2 1 1 H 3,4-diMeO-phenyl H sgl H 553 2 1 1 H 2,4-diCl-phenyl H sgl H 554 2 1 1 H 3,4-diCl-phenyl H sgl H 555 2 1 1 H 2,5-diCl-phenyl H sgl H 556 2 1 1 H 2-CF3-phenyl H sgl H 557 2 1 1 H 2-Me-phenyl H sgl H 558 2 1 1 H 2-Cl-phenyl H sgl H 559 2 1 1 H 3-F-phenyl H sgl H 560 2 1 1 H phenyl H sgl H 561 2 1 1 H 2-CF3-4-EtO-phenyl H sgl H 562 2 1 1 H 2-CF3-4-iPrO-phenyl H sgl H 563 2 1 1 H 2-MeO-4-iPr-phenyl H sgl H 564 2 1 1 H 2-F-4-Cl-phenyl H sgl H 565 2 1 1 H 2-Cl-4-MeO-phenyl H sgl H 566 2 1 1 H 2-CHO-phenyl H sgl H 567 2 1 1 H 2-CHO-4-MeO-phenyl H sgl H 568 2 1 1 H 2-CH2(OH)-4-MeO- H sgl H phenyl 569 2 1 1 H 2-CH2(OH)-phenyl H sgl H 570 2 1 1 H 2-CF3-4-NHMe- H sgl H phenyl 571 2 1 1 H 2-CF3-4-NH2-phenyl H sgl H 572 2 1 1 H 2-C(═
O)Me-phenylH sgl H 573 2 1 1 H 2-C(═
O)Me-4-MeO-H sgl H phenyl 574 2 1 1 H 2-CH(Me)(OH)-phenyl H sgl H 575 2 1 1 H 2-CH(Me)(OH)-4- H sgl H MeO-phenyl 576 2 1 1 H 2-CF3-4-OH-phenyl H sgl H 577 2 1 1 H 2-CF3-4-O(C═
O)Me-H sgl H phenyl or pharmaceutically acceptable salt forms thereof.
-
-
12. A compound of formula (I):
-
or steroisomers or pharmaceutically acceptable salt forms thereof, wherein; b is a single bond;
X is —
O—
, —
S—
, —
S(═
O)—
, or —
S(═
O)2—
,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 1-2 R2, but R2 cannot be alkyl;
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 —
CH(OH)2,—
C(ethylenedioxy)R2,—
OR2,—
SR2,—
NR2R3,—
C(O)R2,—
C(O)N2R3,—
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 C3-4 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, C1-4 alkynyl, C1-4 alkoxy, C1-4 haloalkyl, C3-6 cycloalkyl, and aryl 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;
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, (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;
p1 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, CF3SO2R45, 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 heterocycle 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 R45, 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)NHC(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)(C1-4alkyl), and —
C(═
O)H;
k is 1 or 2;
m is 0, 1, or 2; and
n is 1 or 2;
provided when m is 0 or 1 then k is 1 or 2;
provided when m is 2 then l is 1;
provided that when b is a single bond;
n is 1 or 2;
m is 1;
k is 1;
X is O or S; and
R1 is C1-4 alkyl or cyclopropyl, then R8 is a substituent other than H.- View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 23, 25, 26, 27, 28, 29, 30)
wherein: -
b is a single bond;
X is —
S—
or —
O—
;
R1 is selected from —
C(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)2O(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-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)3NHC(═
O)(phenyl),—
(CH2)2(NMeC(═
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)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-NH4-4-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-indazol-1-yl),—
(CH2)3(5-F-1H-indazol-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-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)C(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, trifluromethyl, 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-, p2 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 1 or 2.
-
19. A compound of claim 18 of Formula (II-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-(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-pyridyl),—
(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(═
)(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)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-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, isopropyoxy, 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 1 or 2.
-
-
20. A compound of claim 18 of Formula (III-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)(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-fluorophenyl),—
(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-incolyl),—
(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)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-NHCO2-Et-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, 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—
, isopropyl-C(═
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 1 or 2.
-
-
23. 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, and sleep disorders;
- comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claims 12-20, or a pharmaceutically acceptable salt thereof.
-
25. A method for treating schizophrenia comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claims 12-20 or a pharmaceutically acceptable salt thereof.
-
26. A method for treating depression comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claims 12-20 or a pharmaceutically acceptable salt thereof.
-
27. A compound of claim 12 selected from the compounds disclosed in Table 1:
-
TABLE 1 Ex # R7 R8 R9 b R1 25 H H H sgl —
C(═
O)(3,4-diMeO-phenyl)26 H H H sgl —
C(═
O)(2,5-diMeO-phenyl)27 H H H sgl —
C(═
O)(3,5-diMeO-phenyl)28 H H H sgl 2,6-diMeO-benzyl 29 H H H sgl 2,4-diMeO-benzyl 30 H H H sgl 2,4,6-triMeO-benzyl 31 H H H sgl 2,3-diMeO-benzyl 32 H H H sgl 2,4,5-triMeO-benzyl 33 H H H sgl cyclohexylmethyl 34 H H H sgl 2,3,4-triMeO-benzyl 35 H H H sgl 3,4-diMeO-benzyl 36 H H H sgl 3,4,5-triMeO-benzyl 39 H H H sgl —
CO2Et40 H —
C(═
O)CH3H sgl —
CO2Et41 H —
NHC(═
O)CH3H sgl —
CO2Et42 H H H sgl —
CH2CH2(4-F-phenyl)46 H H H sgl pentyl 47 H H H sgl hexyl 50 H H H sgl 2-pentyl 51 H H H sgl 2-hexyl 53 H H H sgl 2-Me-butyl 54 H H H sgl 2-Me-pentyl 55 H H H sgl 2-Et-butyl 56 H H H sgl 3-Me-pentyl 57 H H H sgl 3-Me-butyl 58 H H H sgl 4-Me-pentyl 59 H H H sgl cyclopropylmethyl 60 H H H sgl cyclobutylmethyl 61 H H H sgl cyclohexylmethyl 62 H H H sgl 2-propenyl 63 H H H sgl 2-Me-2-propenyl 64 H H H sgl trans-2-butenyl 65 H H H sgl 3-Me-butenyl 66 H H H sgl 3-butenyl 67 H H H sgl trans-2-pentenyl 68 H H H sgl cis-2-pentenyl 69 H H H sgl 4-pentenyl 70 H H H sgl 4-Me-3-pentenyl 71 H H H sgl 3,3-diCl-2-propenyl 72 H H H sgl benzyl 73 H H H sgl 2-Me-benzyl 74 H H H sgl 3-Me-benzyl 75 H H H sgl 4-Me-benzyl 76 H H H sgl 2,5-diMe-benzyl 77 H H H sgl 2,4-diMe-benzyl 78 H H H sgl 3,5-diMe-benzyl 79 H H H sgl 2,4,6-triMe-benzyl 80 H H H sgl 3-MeO-benzyl 81 H H H sgl 3,5-diMeO-benzyl 82 H H H sgl pentafluorobenzyl 83 H H H sgl 2-phenylethyl 84 H H H sgl 1-phenyl-2-propyl 85 H H H sgl trans-3-phenyl-2-propenyl 86 H H H sgl 4-phenylbutyl 87 H H H sgl 4-phenylbenzyl 88 H H H sgl 2-phenylbenzyl 178 Cl H H sgl —
(CH2)3C(═
O)(4-F-phenyl)179 Me H H sgl —
(CH2)3C(═
O)(4-F-phenyl)180 H H H sgl —
(CH2)3S(3-F-phenyl)181 H H H sgl —
(CH2)3CH(OH)(4-F-phenyl)186 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)187 H MeO H sgl —
(CH2)3C(═
O)(4-F-phenyl)192 H H H sgl —
(CH2)3(═
O)(4-Br-phenyl)193 H H H sgl —
(CH2)3SO2(3-F-phenyl)194 H H H sgl —
(CH2)3C(═
O)(4-(3,4-diCl-phenyl)phenyl)197 H H H sgl —
(CH2)3C(═
O)(4-Me-phenyl)198 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)199 H H H sgl —
(CH2)3C(═
O)(4-MeO-phenyl)200 H H H sgl —
(CH2)2C(═
O)(4-F-phenyl)201 H H H sgl —
(CH2)3SO2(4-F-phenyl)202 H H H sgl —
(CH2)3S(═
O)(4-F-phenyl)203 H H H sgl —
(CH2)3O(4-F-phenyl)204 H H H sgl —
(CH2)3O(phenyl)205 H H H sgl —
(CH2)3S(4-F-phenyl)206 H H H sgl —
(CH2)3NH(4-F-phenyl)207 H H H sgl —
(CH2)3N(CH3)(4-F-phenyl)208 H H H sgl —
(CH2)3C(═
O)(4-pyridyl)209 H H H sgl —
(CH2)3C(═
O)(3-pyridyl)214 H H H sgl 215 H H H sgl 219 H H H sgl —
(CH2)3CO2Et220 H H H sgl —
(CH2)4CO2Et221 H H H sgl —
(CH2)3C(═
O)N(CH3)(OCH3)222 H H H sgl —
(CH2)4C(═
O)N(CH3)(OCH3)223 H H H sgl —
(CH2)3C(═
O)(3-Me-4-F-phenyl)224 H H H sgl —
(CH2)3C(═
O)(phenyl)225 H H H sgl —
(CH2)3C(═
O)(4-Cl-phenyl)226 H H H sgl —
(CH2)3C(═
O)(3-Me-phenyl)227 H H H sgl —
(CH2)3C(═
O)(4-tBu-phenyl)228 H H H sgl —
(CH2)3C(═
O)(3,4-diF-phenyl)229 H H H sgl —
(CH2)3C(═
O)(2-MeO-5-F-phenyl)230 H H H sgl —
(CH2)4C(═
O)(phenyl)231 H H H sgl —
(CH2)3C(═
O)(4-F-1-naphthyl)232 H H H sgl —
(CH2)3C(═
O)(benzyl)233 H H H sgl —
(CH2)2C(═
O)NH(4-F-phenyl)234 H H H sgl —
(CH2)3C(═
O)NH(4-F-phenyl)235 H H H sgl —
(CH2)3CH(OH)(4-F-phenyl)236 H H H sgl —
(CH2)3CH(OH)(4-pyridyl)237 H H H sgl —
(CH2)3CH(OH)(2,3-diMeO-phenyl)238 H H H sgl —
(CH2)3C(═
O)(2,3-diMeO-phenyl)239 H H H sgl —
(CH2)4(cyclohexyl)240 H H H sgl —
(CH2)3CH(phenyl)2241 H H H sgl —
CH2CH2CH═
C(phenyl)2242 H H H sgl —
(CH2)3CH(4-F-phenyl)2243 H H H sgl —
CH2CH2CH═
C(4-F-phenyl)2244 H H H sgl —
(CH2)2NHC(═
O)(phenyl)245 H H H sgl —
(CH2)2NHC(═
O)(2-F-phenyl)246 H H H sgl —
(CH2)2NHC(═
O)(4-F-phenyl)247 H H H sgl —
(CH2)3(3-indolyl)248 H H H sgl —
(CH2)3(1-Me-3-indolyl)249 H H H sgl —
CH2CH2(3-indolyl)250 H H H sgl —
(CH2)3(1-indolyl)251 H H H sgl —
(CH2)3(1-indolinyl)252 H H H sgl —
(CH2)3(1-benzimidazolyl)253 H H H sgl 254 H H H sgl 268 H F H sgl —
(CH2)3C(═
O)(4-F-phenyl)286 H H H sgl —
(CH2)2NHO(═
O)(2,4-diF-phenyl)287 H H H sgl —
(CH2)2NMeO(═
O)-phenyl288 H H H sgl —
(CH2)2NMeO(═
O)(2-F-phenyl)289 H H H sgl —
(CH2)2NMeO(═
O)(2,4-diF-phenyl)290 H H H sgl —
(CH2)2NMeO(═
O)(4-F-phenyl)291 H H H sgl —
(CH2)3(1H-1,2,3-benzotriazol-1-yl)292 H H H sgl —
(CH2)3(1H-1,2,3-benzotriazol-2-yl)293 H H H sgl 294 H H H sgl 295 H H H sgl 296 H H H sgl 297 H H H sgl —
(CH2)2(1H-1,2,3-benzotriazol-1-yl)298 H H H sgl —
(CH2)2(1H-1,2,3-benzotriazol-2-yl)299 H H H sgl —
(CH2)3(3,4-dihydro-1(2H)-quinolyl)300 H H H sgl —
CH2CH2CH═
CMe(4-F-phenyl)301 H H H sgl —
(CH2)2(2,3-dihydro-1H-inden-2-yl)302 H H H sgl —
(CH2)3C(═
O)(2-NH2-phenyl)303 H H H sgl —
(CH2)3C(═
O)(2-NH2-phenyl)304 H H H sgl —
(CH2)3C(═
O)(2-NH2-5-F-phenyl)305 H H H sgl —
(CH2)3C(═
O)(2-NH2-3-F-phenyl)306 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-Cl-phenyl)307 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-OH-phenyl)308 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-Br-phenyl)309 H H H sgl —
(CH2)3(1H-indazol-3-yl)310 H H H sgl —
(CH2)3(5-F-1H-indazol-3-yl)311 H H H sgl —
(CH2)3(7-F-1H-indazol-3-yl)312 H H H sgl —
(CH2)3(6-Cl-1H-indazol-3-yl)313 H H H sgl —
(CH2)3(6-Br-1H-indazol-3-yl)314 H H H sgl —
(CH2)3C(═
O)(2-NHMe-phenyl)315 H H H sgl —
(CH2)3(1-benzothien-3-yl)355 H H H sgl 356 H H H sgl —
(CH2)3(6-F-1H-indol-1-yl)357 H H H sgl —
(CH2)3(5-F-1H-indol-1-yl)358 H H H sgl —
(CH2)3(6-F-2,3-dihydro-1H-indol-1-yl)359 H H H sgl —
(CH2)3(5-F-2,3-dihydro-1H-indol-1-yl)360 H H H sgl —
(CH2)3(6-F-1H-indol-3-yl)361 H H H sgl —
(CH2)3(6-F-1H-indol-3-yl)362 H H H sgl —
(CH2)3(5-F-1H-indol-3-yl)363 H H H sgl —
(CH2)3(5-F-1H-indol-3-yl)364 H H H sgl —
(CH2)3(9H-purin-9-yl)365 H H H sgl —
(CH2)3(7H-purin-7-yl)366 H H H sgl 367 H H H sgl —
(CH2)3(6-F-1H-indazol-3-yl)368 H H H sgl —
(CH2)3(6-F-1H-indazol-3-yl)369 H H H sgl —
(CH2)3(6-F-1H-indazol-3-yl)370 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl)371 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl)372 H H H sgl —
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl)373 H H H sgl —
(CH2)3C(═
O)(2-NHO(═
O)Me-4-F-phenyl)374 H H H sgl —
(CH2)3C(═
O)(2-NHO(═
O)Me-4-F-phenyl)375 H H H sgl —
(CH2)3C(═
O)(2-NHCO2Et-4-F-phenyl)376 H H H sgl —
(CH2)3C(═
O)(2-NHO(═
O)NHEt-4-F-phenyl)377 H H H sgl —
(CH2)3C(═
O)(2-NHCHO-4-F-phenyl)378 H H H sgl —
(CH2)3C(═
O)(2-OH-4-F-phenyl)379 H H H sgl —
(CH2)3C(═
O)(2-MeS-4-F-phenyl)442 H H H sgl —
(CH2)3C(═
O)(2-NHSO2Me-4-F-phenyl)485 H H H sgl —
(CH2)2C(Me)CO2Me486 H H H sgl —
(CH2)2C(Me)C(OH)(4-F-phenyl)2487 H H H sgl —
(CH2)2C(Me)C(OH)(4-Cl-phenyl)2489 H H H sgl —
(CH2)2C(Me)C(═
O)(4-F-phenyl)490 H H H sgl —
(CH2)2C(Me)C(═
O)(2-MeO-4-F-phenyl)491 H H H sgl —
(CH2)2C(Me)C(═
O)(3-Me-4-F-phenyl)492 H H H sgl —
(CH2)2C(Me)C(═
O)(2-Me-phenyl)493 H H H sgl —
(CH2)2C(Me)C(═
O)phenyl591 Cl H H sgl —
(CH2)3C(═
O)(2-NH2-4-phenylor pharmaceutically acceptable salt forms thereof.
-
-
28. A compound of claim 12 selected from the compounds closed in Table 2:
-
TABLE 2 Ex # n k m R7 R8 R9 b R1 472 2 2 1 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)473 2 2 1 H H H sgl —
(CH2)3O(4-F-phenyl)474 2 2 1 H H H sgl —
(CH2)3(6-F-benzisoxazol-3-yl) 475 2 2 1 H H H sgl —
(CH2)3C(═
O)(4-pyridyl)483 2 2 1 H Br H sgl —
(CH2)3C(═
O)(4-F-phenyl)484 2 2 1 H Br H sgl —
(CH2)3O(4-F-phenyl)488 1 2 1 H Br H sgl —
CO2—
tBuor pharmaceutically acceptable salt forms thereof.
-
-
29. A compound of claim 12 selected from the compounds closed in Table 3:
-
TABLE 3 Ex # n k m R7 R8 R9 b R1 182 1 1 1 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl) 266 1 1 1 H H Me sgl —
(CH2)3C(═
O)(4-F-phenyl) 270 1 1 1 H H H sgl —
(CH2)3O(4-F-phenyl) 272 1 1 1 H H H sgl H 494 1 1 1 H H H sgl —
(CH2)3C(═
O)(2-NH2-phenyl) 495 1 1 1 H H H sgl —
(CH2)3C(═
O)(2-NH2-phenyl) 496 1 1 1 H H H sgl —
(CH2)3(1H-indazol-3-yl)528 1 1 1 H H H sgl —
(CH2)3(6-F-1H-indazol-3-yl) 529 1 1 1 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl) 530 1 1 1 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl) 531 1 1 1 H H H sgl —
(CH2)3C(═
O)(2-OH-4-F-phenyl) 539 1 2 1 H H H sgl —
(CH2)3O(4-F-phenyl)540 1 2 1 H H H sgl —
(CH2)3(6-F-1,2-benzisoxazol-3-yl) 544 2 1 1 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl) 546 1 2 1 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl or pharmaceutically acceptable salt forms thereof.
-
-
30. A compound of claim 12 selected from the compounds closed in Table 4:
-
TABLE 4 Ex # R7 R8 R9 b R1 185 H H CF3 sgl —
(CH2)4(4-F-phenyl)188 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)213 H CH3 H sgl —
(CH2)3C(═
O)(4-F-phenyl)438 H H H sgl —
(CH2)3C(═
O)((2-NH2-phenyl)439 H H H sgl —
(CH2)3C(═
O)((2-NH2-phenyl)440 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl)441 H H H sgl —
(CH2)3C(═
O)(2-NH2-4-F-phenyl)456 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)457 H H H sgl —
(CH2)3C(═
O)(4-F-phenyl)or pharmaceutically acceptable salt forms thereof.
-
-
Specification