1. A compound having Formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
Z1 is selected from the group consisting of N and N-oxide and Z2 is CR1b;
R1a and R1b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) halogen;
c) hydroxy;
d) cyano;
e) optionally substituted alkyl;
f) alkoxy;
g) haloalkoxy; and
h) haloalkyl;
A1 is selected from the group consisting of:
a) aryl, which is unsubstituted or substituted with one to five substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl, or two adjacent positions are taken together to form a cycloalkyl or heterocyclo ring; and
b) heteroaryl, which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
X is selected from the group consisting of:
a) \u2014O\u2014;
b) \u2014S\u2014;
c) \u2014SO\u2014;
d) \u2014SO2\u2014
e) \u2014NR4;
f) \u2014SO2NH\u2014; and
g) \u2014NHSO2\u2014;
wherein:
R4 is selected from the group consisting of hydrogen and optionally substituted alkyl;
A2 is aryl, which is unsubstituted or substituted with one to five substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl, or two adjacent positions are taken together to form a cycloalkyl or heterocyclo ring;
G is:
wherein:
R5a and R5b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
c) cycloalkyl, which is unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
d) heterocyclo, which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, carboxamido, alkylcarbonyl, arylcarbonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
e) aryl, which is unsubstituted or substituted with one to five substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl, or two adjacent positions are taken together to form a cycloalkyl or heterocyclo ring;
f) heteroaryl, which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
g) hydroxyalkyl; and
h) unsubstituted (heterocyclo)alkyl;
R6a and R6b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) (heterocyclo)alkyl;
c) (carboxamido)alkyl; and
d) (cyano)alkyl;
R7 is \u2014(CH2CH2O)o\u2014R15c;
R8a and R8b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl; and
c) \u2014(CH2CH2O)p\u2014R15d;
L is \u2014O\u2014;
R15c, and R15d, which are identical or different, are selected from the group consisting of hydrogen and unsubstituted alkyl;
o, and p, each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11;
w is 0;
x and y are each independently 1, 2, 3, or 4;
E is selected from the group consisting of:
a) hydrogen;
b) heteroaryl, which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
wherein:
R17a and R17b , which are different from each other, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
c) \u2014SO2R24a;
d) \u2014COR24b;
e) aryl, which is unsubstituted or substituted by carboxy;
f) heteroaryl, which is unsubstituted or substituted by carboxy or cyano;
g) (heterocyclo)alkyl;
h) (heteroaryl)alkyl;
i) (amino)alkyl;
j) (alkylamino)alkyl;
k) (dialkylamino)alkyl;
l) (carboxamido)alkyl;
m) (cyano)alkyl; and
n) hydroxyalkyl;
R18a and R18b , which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
c) unsubstituted cycloalkyl;
d) unsubstituted aryl;
e) unsubstituted heteroaryl;
f) unsubstituted (heterocyclo)alkyl;
g) (heteroaryl)alkyl; and
h) (dialkylamino)alkyl;
R19 is selected from the group consisting of hydrogen and unsubstituted alkyl;
R20a and R20b , which are identical or different, are selected from the group consisting of hydrogen and unsubstituted alkyl, wherein at least one of R20a and R20b is unsubstituted alkyl;
R21a is selected from the group consisting of hydrogen and alkyl;
R21b and R21c , which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) alkyl, which is unsubstituted or substituted by carboxy;
c) unsubstituted cycloalkyl;
d) unsubstituted aryl;
e) unsubstituted heteroaryl;
f) (heterocyclo)alkyl;
g) (heteroaryl)alkyl; and
h) (dialkylamino)alkyl;
R22 is selected from the group consisting of hydrogen and alkyl;
R24a is selected from the group consisting of unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl;
R24b is selected from the group consisting of unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl;
t and u are each independently 0, 1, 2, or 3; and
v is 1, 2, or 3;
wherein:
1) when G is G-1, then E is hydroxyalkyl, E-1, or E-5; or
2) when E is hydrogen, then G is G-2, G-3, or G-4.
2. The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:
Z1 is selected from the group consisting of N and N-oxide and Z2 is CH;
R1a is hydrogen;
Al is selected from the group consisting of unsubstituted or substituted aryl and unsubstituted or substituted heteroaryl;
X is selected from the group consisting of:
a) \u2014O\u2014;
b) \u2014SO2NH\u2014; and
c) \u2014NHSO2\u2014
A2 is unsubstituted phenyl;
G is selected from the group consisting of:
wherein:
R5a and R5b are hydrogen;
R6a is selected from the group consisting of:
a) (herterocyclo)alkyl;
b) (carboxamido)alkyl; and
c) (cyano)alkyl);
R6b is selected from the group consisting of hydrogen and (cyano)alkyl;
R7 is \u2014(CH2CH2O)o\u2014R15c;
R8a and R8b are hydrogen;
L is \u2014O\u2014;
R15c is selected from the group consisting of hydrogen and unsubstituted alkyl;
o is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11;
w is 0;
x is 1 or 2;
y is 1;
E is selected from the group consisting of:
wherein:
R17a is selected from the group consisting of hydrogen and alkyl;
R17b is selected from the group consisting of:
a) aryl, which is unsubstituted or substituted by carboxy;
b) heteroaryl, which is unsubstituted or substituted by carboxy or cyano;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) hydroxyalkyl; and p2 k) -SO2R24a
R18a and R18b are hydrogen or unsubstituted alkyl;
R21a is selected from the group consisting of hydrogen and alkyl;
R21b and R21c , which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) alkyl, which is unsubstituted or substituted by carboxy;
c) unsubstituted cycloalkyl;
d) unsubstituted aryl;
e) unsubstituted heteroaryl;
f) (heterocyclo)alkyl;
g) (heteroaryl)alkyl; and
h) (dialkylamino)alkyl;
t is 0 or 1; and
u is 0.
3. The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein:
A1 is selected from the group consisting of or substituted aryl and unsubstituted or substituted heteroaryl;
X is \u2014O\u2014; and
A2 is unsubstituted or substituted phenyl.
4. The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein A1-X-A2- is:
wherein:
R23a,R 23b, R23c, R2 3d, R23e, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) halo;
c) nitro;
d) cyano;
e) hydroxy;
f) amino;
g) alkylamino;
h) dialkylamino;
i) haloalkyl;
j) hydroxyalkyl;
k) alkoxy;
l) haloalkoxy;
m) aryloxy;
n) aralkyloxy;
o) alkylthio;
p) carboxamido;
q) sulfonamido;
r) alkylcarbonyl;
s) arylcarbonyl;
t) alkylsulfonyl;
u) arylsulfonyl;
v) ureido;
w) guanidino;
x) carboxy;
y) carboxyalkyl;
z) alkyl;
aa) unsubstituted cycloalkyl;
bb) unsubstituted alkenyl;
cc) unsubstituted alkynyl;
dd) unsubstituted aryl;
ee) unsubstituted heteroaryl; and
ff) unsubstituted heterocyclo; or
R23a and R23b, or R23b and R23c, or R23c and R23d, or R23d and R23e,taken together with the carbon atoms to which they are attached form a 5- or 6-membered cycloalkyl or heterocyclo group.
5. The compound of claim 1 having Formula XXIV:
or a pharmaceutically acceptable salt or solvate thereof.
6. A compound having Formula XXXII:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
E is selected from the group consisting of:
R5a and R5b are H;
Al is selected from the group consisting of:
a) aryl, which is unsubstituted or substituted with one to five substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl, or two adjacent positions are taken together to form a cycloalkyl or heterocyclo ring; and
b) heteroaryl, which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, carboxamido, sulfonamido, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, ureido, guanidino, carboxy, carboxyalkyl, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl;
R17a and R17b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
c) \u2014SO2R24a;
d) \u2014COR R24b;
e) aryl, which is unsubstituted or substituted by carboxy;
f) heteroaryl, which is unsubstituted or substituted by carboxy or cyano;
g) (heterocyclo)alkyl;
h) (heteroaryl)alkyl;
i) (amino)alkyl;
j) (alkylamino)alkyl;
k) (dialkylamino)alkyl;
I) (carboxamido)alkyl;
m) (cyano)alkyl; and
n) hydroxyalkyl;
t is 0, 1, 2, or 3;
R24a is selected from the group consisting of unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl; and
R24b is selected from the group consisting of unsubstituted alkyl, unsubstituted cycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl.
7. A compound selected from the group consisting of:
2-(2,5,8,11-tetraoxadodecyl)-6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridine;
2-(2,5,8,11,14,17,20,23-octaoxatetracosyl)-6-(4-(4-(trifluoromethyl)phenoxy) phenyl)pyridine;
1-(6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(S)-1-(6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(R)-1-(6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(S)-4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)benzonitrile;
(R)-4-(2-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)-N-isopropylpiperazine-1-carboxamide;
4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)benzonitrile;
4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl)benzonitrile;
2-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-5-(trifluoromethyl)benzonitrile;
(R)-4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl)benzonitrile;
5-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-2-(trifluoromethyl)benzonitrile;
(R)-4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)benzonitrile;
(R)-5-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-2-(trifluoromethyl)benzonitrile;
1 -(6-(4-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
1 -(6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
1 -(6-(4-((6-methylpyridin-3-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(S)-5-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-2-(trifluoromethyl)benzonitrile;
(1 R,1 \u2018R)-1 ,1 \u2019-(6-(4-(4-fluorophenoxy)phenyl)pyridine-2,4-diyl)bis(ethane-1,2-diol;
1 -(4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl)phenyl) ethanone;
(R)-1 -(6-(4-(4-fluorophenoxy)phenyl)-4-(piperazin-1 -yl)pyridin-2-yl)ethane-1,2-diol;
(S)-4-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl)benzonitrile;
(R)-1 -(6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(S)-1 -(6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
4-(4-(4,6-bis((S)-1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl) benzonitrile;
(1 S,1 \u2018S)-1 ,1 \u2019-(6-(4-(4-fluorophenoxy)phenyl)pyridine-2,4-diyl)bis(ethane-1,2-diol;
1 -(6-(4-((6-methylpyridin-3-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
4-(4-(4,6-bis((R)-1,2-dihydroxyethyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl) benzonitrile;
1 -(6-(4-((3-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)ethane-1,2-diol;
(S)-4-(1,2-dihydroxyethyl)-6-(4-(4-(trifluoromethyl)phenoxy)phenyl)picolinamide;
(S)-6-(4-(4-cyano-3-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(S)-6-(4-(4-carbamoyl-2-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(S)-6-(4-(3-cyano-4-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(R)-6-(4-(3-cyano-4-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(S)-6-(4-(4-cyano-2-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(R)-6-(4-(4-cyano-2-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
(S)-6-(4-(4-cyanophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide;
(R)-6-(4-(4-cyanophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide;
(S)-6-(4-(5-chloro-2-fluorophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide;
(R)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)-N-(2-(piperidin-1 -yl)ethyl)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(methyl(phenyl)amino)picolinamide;
4-((2-cyanoethyl)(phenyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((pyridin-3-ylmethyl)amino)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((pyridin-4-ylmethyl)amino)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((pyridin-2-ylmethyl)amino)picolinamide;
4-((2-(1 ,1 -dioxidothiomorpholino)ethyl)amino)-6-(4-(4-fluorophenoxy)phenyl) picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((pyrimidin-2-ylmethyl)amino)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(methylsulfonamidomethyl)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(piperazin-1 -ylmethyl)picolinamide;
4-(((1 -(2-amino-2-oxoethyl)piperidin-4-yl)methyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((2-morpholinoethyl)amino)picolinamide;
4-((3-(1 H-imidazol-1 -yl)propyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-(4-carbamoylpiperidin-1 -yl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((piperidin-4-ylmethyl)amino)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-((2-(2-oxoimidazolidin-1-yl)ethyl)amino)picolinamide;
1 -(2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)piperidine-4-carboxylic acid;
6-(4-(4-fluorophenoxy)phenyl)-4-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl) picolinamide;
1 -(2-(((6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)methyl)amino)ethyl) imidazolidin-2-one;
1 -(2-(((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methyl)amino)ethyl)imidazolidin-2-one;
2-(4-(6-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl)pyridin-2-yl)phenoxy)-5-(trifluoromethyl)benzonitrile;
1 -(2-((2-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ethyl)amino)ethyl)imidazolidin-2-one;
4-(4-(6-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl)pyridin-2-yl)phenoxy)-3-(trifluoromethyl) benzonitrile;
1 -(2-(((6-(4-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl) methyl)amino)ethyl)imidazolidin-2-one;
4-(4-(6-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl)pyridin-2-yl)phenoxy) benzonitrile;
1 -(2-(((6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)methyl)amino) ethyl)imidazolidin-2-one;
2-(((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methyl)(2-(2-oxoimidazolidin-1 -yl) ethyl)amino)acetonitrile;
5-(4-(6-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl)pyridin-2-yl)phenoxy)-2-(trifluoromethyl)benzonitrile;
1 -(2-(((6-(4-(4-(methylsulfonyl)phenoxy)phenyl)pyridin-2-yl)methyl)amino)ethyl) imidazolidin-2-one;
2-(((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methyl)(2-(2-oxoimidazolidin-1 -yl)ethyl)amino)acetamide;
4-(2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)-N-isopropylpiperazine-1 -carboxamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(4-(pyrimidin-2-yl)piperazin-1 -yl)picolinamide;
4-(4-(2-amino-2-oxoethyl)piperazin-1 -yl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-(2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)piperazine-1 -carboxamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)piperazin-1 -yl)picolinamide;
(6-(4-(4-fluorophenoxy)phenyl)-4-(piperazin-1 -yl)pyridin-2-yl)(piperazin-1 -yl)methanone;
6-(4-(4-fluorophenoxy)phenyl)-4-(hydroxymethyl)-N-(2-(piperidin-1 -yl)pethyl)picolinamide;
4-(4-carbamimidoylpiperazin-1 -yl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-(2-cyano-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)-N-isopropylpiperazine-1 -carboxamide;
4-(2-cyano-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)piperazine-1 -carboximidamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(3-phenylureido)picolinamide;
2-(4-(4-fluorophenoxy)phenyl)-6-((2-(piperidin-1 -yl)ethyl)carbamoyl)isonicotinic acid;
6-(4-(4-fluorophenoxy)phenyl)-N-(2-(piperidin-1 -yl)ethyl)-4-(1 H-tetrazol-5-yl)picolinamide;
2-(3-(2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)ureido)acetic acid;
(S)-2-({6-4-(4-Fluoro-phenoxyl)-phenyl-pyridin-2-yl-methyl}-amino)propionamide;
(R)-2-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)isonicotinamide;
(S)-6-(4-(3-cyano-4-(trifluoromethyl)phenoxy)phenyl)-N-(2,3-dihydroxypropyl) picolinamide;
4-((2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)(methyl)amino)benzoic acid;
4-((carboxymethyl)(phenyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid;
1 -(2-carboxy-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)-1 H-indole-3-carboxylic acid;
6-((2-cyanoethyl)(phenyl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinic acid;
(S)-6-(1,2-dihydroxyethyl)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
(R)-6-(1,2-dihydroxyethyl)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
(S)-2-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)isonicotinamide;
6-((2-amino-2-oxoethyl)(phenyl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-(4-cyano-1 H-indol-1 -yl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
6-(4-cyano-1 H-indol-1 -yl)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-(4-cyano-1H-indol-1-yl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid;
4-((2-amino-2-oxoethyl)(phenyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(R)-4-(1,2-dihydroxyethyl)-6-(4-(4-(trifluoromethyl)phenoxy)phenyl)picolinamide;
2-(4-((2-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyridine-4-yl)methyl)piperazin-1 -yl) acetic acid;
1-(2-(((2-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)methyl)amino)ethyl)imidazolidin-2-one;
6-(4-(4-fluorophenoxy)phenyl)-4-(((2-(2-oxoimidazolidin-1 -yl)ethyl)amino)methyl) picolinonitrile;
2-(4-(4-fluorophenoxy)phenyl)-6-methyl-N-(2-(piperidin-1-yl)ethyl)isonicotinamide;
2-(5-(2-(4-(4-fluorophenoxy)phenyl)-6-methylpyridin-4-yl)-2H-tetrazol-2-yl) acetamide;
2-(4-(2-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridine-4-yl)piperazin-1-yl)acetamide;
4-((3-(1 H-imidazol)-1 -yl)propyl)amino)-6-(4-(4-fluorophenoxy)phenylpicolinonitrile;
(R)-1-6-(4-(4-fluorophenoxy)phenyl)-4-((2-morpholinoethyl)amino)pyridine-2-yl) ethan-1,2-diol (S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy) phenyl)picolinonitrile;
4-(4-(4-fluorophenoxy)phenyl)-6-(methyl(phenyl)amino)picolinamide;
6-(4-(4-fluorophenoxy)phenyl)-4-(methyl(phenyl)amino)picolinic acid;
6-((2-cyanoethyl) (phenyl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-((6-carbamoyl-4-(4-(4-fluorophenoxy) phenyl)pyridin-2-yl)(methyl)amino)benzoic acid;
4-((4-carboxyphenyl)(methyl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid;
4-((2-cyanoethyl) (phenyl)amino)-6-(4-(4fluorophenoxy) phenyl)picolinic acid;
4-(4-(4-fluorophenoxy)phenyl)-6-(methyl (phenyl)amino)picolinic acid;
6-((4-carboxyphenyl) (methyl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinic acid;
6-((carboxymethyl) (phenyl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinic acid;
6-(4-(4-fluorophenoxy) phenyl)-1\u2032,2\u2032,3\u2032,6\u2032-tetrahydro-4,4\u2032-bipyridine-2-carboxamide;
(R)-6-(4-(5-chloro-2-fluorophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide;
(S)-4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)-N-(4-fluorophenyl)benzenesulfonamide;
6-chloro-N-(1,3-dihydroxypropan-2-yl)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
6-(4-cyano-1H-indol-1-yl)-4-(4-(4-fluorophenoxy)phenyl)picolinic acid;
(R)-6-(4-(4-cyano-3-(trifluoromethyl)phenoxy)phenyl)-4-(1,2-dihydroxyethyl) picolinamide;
6-((1,3-dihydroxypropan-2-yl)amino)-4-(4-(4-fluorophenoxy)phenyl)picolinamide;
4-((1S,2S)-1,2-dihydroxypropyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
1-(2-carboxy-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)-1 H-indole-6-carboxylic acid;
4-((1 R,2R)-1,2-dihydroxypropyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(R)-4-(1,2-dihydroxyethyl)-6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)picolinamide;
4-((1,3-dihydroxypropan-2-yl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(R)-4-(2,3-dihydroxypropyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(S)-4-(2,3-dihydroxypropyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide;
(S)-N-(4-(6-(1,2-dihydroxyethyl)pyridin-2-yl)phenyl)-4-fluorobenzenesulfonamide;
(R)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinonitrile;
(S)-4-(1,2-dihydroxyethyl)-6-(5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl) picolinamide;
(S)-6-(4-(4-chloro-2-fluorophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide; or
(R)-6-(4-(4-chloro-2-fluorophenoxy)phenyl)-4-(1,2-dihydroxyethyl)picolinamide;
4-((R)-1,2-dihydroxy-ethyl)-6–(4-fluoro-phenoxy)-phenyl-pyridine-2-carboxylic acid amide;
({6-carbamoyl-4-4-(4-fluoro-phenoxy)-phenyl-pyridin-2-yl}phenyl-amino)-acetic acid;
3-({6-carbamoyl-4-4-(4-fluoro-phenoxy)-phenyl-pyridin-2-yl}phenyl-amino)-propionic acid;
3-({2-carbamoyl-6-4-(4-fluoro-phenoxy)-phenyl-pyridin-4-yl}phenyl-amino)-propionic acid;
4-4-(4-cyano-phenoxy)-phenyl-6-(methyl-phenyl-amino)-pyridine2-carboxylic acid amide;
6-4-(4-cyano-phenoxy)-phenyl-4-(methyl-phenyl-amino)-pyridine-2-carboxylic acid amide;
6-(methyl-phenyl-amino)-4-4-(4-trifluoromethyl-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
4-(methyl-phenyl-amino)-6-4-(4-trifluoromethyl-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
6-4-(4-fluoro-phenoxy)-phenyl-4-{phenyl-2-(2H-tetrazol-5-yl)-ethyl-amino}-pyridine-2-carboxylic acid amide;
4-4-(4-fluoro-phenoxy)-phenyl-6-{phenyl-2-(2H-tetrazol-5-yl)-ethyl-amino}-pyridine-2-carboxylic acid amide;
6-4-(4-fluoro-phenoxy)-phenyl-4-{phenyl-2-(2H-tetrazol-5-yl)ethyl-amino}-pyridine-2-carboxylic acid;
4-4-(4-fluoro-phenoxy)-phenyl-6-{phenyl-2-(2H-tetrazol-5-) ethylamino}-pyridine-2-carboxylic acid;
4-((S)-1,2-dihydroxy-ethyl)-6-(4\u2032-fluoro-biphenyl-4-yl) pyridine-2-carboxylic acid amide;
4-((R)-1,2-dihydroxy-ethyl)-6-(4\u2032-fluoro-biphenyl-4-yl)pyridine-2-carboxylic acid amide;
6-((S)-1,2-dihydroxy-ethyl)-4-4-(4-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
6-((R)-1,2-dihydroxy-ethyl)-4-4-(4-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
6-((S)-1,2-dihydroxy-ethyl)-4-4-(3-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
4-((S)-1,2-dihydroxy-ethyl)-6-4-(4-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
6-((S)-1,2-dihydroxy-ethyl)-4-(4\u2032-fluoro-biphenyl-4-yl)pyridine-2-carboxylic acid amide;
4-((R)-1,2-dihydroxy-ethyl)-64-(4-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
6-((R)-1,2-dihydroxy-ethyl)-4-(4\u2032-fluoro-biphenyl-4-yl) pyridine-2-carboxylic acid amide;
4-((S)-1,2-dihydroxy-ethyl)-6-4-(3-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
4-((R)-1,2-dihydroxy-ethyl)-6-4-(3-trifluoromethoxy-phenoxy)phenyl-pyridine-2-carboxylic acid amide;
(S)-2-((2-cyano-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)amino)propanamide;
(S)-2-((4-cyano-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)propanamide;
(S)-4-((1 -amino-1 -oxopropan-2-yl)amino)-6-(4-(4-fluorophenoxy)phenyl)picolinamide; and
(S)-2-((2-((S)-1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-4-yl)amino) propanamide;
or a pharmaceutically acceptable salt or solvate thereof.
8. A pharmaceutical composition, comprising the compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.
9. A method for treating in a mammal, comprising administering an effective amount of a compound as claimed in claim 1, or a pharmaceutically acceptable salt or solvate thereof, to a mammal in need of such treatment.
10. A method of modulating sodium channels in a mammal, comprising administering to the mammal at least one compound as claimed in claim 1.
11. The method of claim 10, wherein the Nav1.7 sodium channel is modulated.
12. A method of preparing a pharmaceutical composition, comprising admixing a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or prodrug,with a pharmaceutically acceptable carrier.
13. The compound of claim 5 having Formula XXV:
or a pharmaceutically acceptable salt or solvate thereof.
14. The compound of claim 5 having Formula XXVI:
or a pharmaceutically acceptable salt or solvate thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A voice conference apparatus comprising:
a communication unit that transmits and receives a first voice signal to and from another apparatus via a network;
an output unit that reproduces the first voice signal received by the communication unit and outputs the reproduced first voice signal as a first voice;
an input unit that collects the first voice and a second voice generated by a voice source, as a second voice signal;
a separating unit that separates the second voice signal into a third voice signal originated from the first voice and a fourth voice signal originated from the second voice; and
a selecting unit that selects one of the third voice signal and the fourth voice signal,
wherein the communication unit transmits the one of the third voice signal and the fourth voice signal selected by the selecting unit to the other apparatus, the voice conference apparatus further comprising:
a first measuring unit that measures a voice level of the first voice signal received by the communication unit;
a first adjusting unit that adjusts the voice level of the first voice signal in accordance with the voice level of the first voice signal measured by the first measuring unit;
a second measuring unit that is disposed near the output unit and measures a voice level of the first voice; and
a second adjusting unit that adjusts the voice level of the third voice signal in accordance with the voice level of the first voice measured by the second measuring unit.
2. The voice conference apparatus according to claim 1,
wherein the selecting unit is capable of being controlled by the other apparatus.
3. The voice conference apparatus according to claim 1,
wherein the first voice signal received by the communication unit includes a digital signal.
4. The voice conference apparatus according to claim 3, further comprising:
a decoding unit that decodes the digital signal; and
an encoding unit that encodes the one of the first voice signal and the second voice signal selected by the selecting unit into a digital signal.
5. A method for confirming a communication in a voice conference system including a first apparatus and a second apparatus connected to the first apparatus via a network, the method comprising:
collecting a first voice generated from a first voice source around the first apparatus as a first voice signal;
transmitting the first voice signal to the second apparatus from the first apparatus;
reproducing the transmitted first voice signal by the second apparatus;
outputting the reproduced first voice signal as a second voice;
collecting the second voice and a third voice generated from a second voice source around the second apparatus as a second voice signal at the second apparatus;
separating the second voice signal into a third voice signal originated from the second voice and a fourth voice signal originated from the third voice;
transmitting the third voice signal to the first apparatus;
reproducing the transmitted third voice signal;
determining whether or not the first voice is normally reproduced by the second apparatus by comparing the first voice generated from the first voice source around the first apparatus with the reproduced third voice signal;
measuring a voice level of the first voice signal to be transmitted to the second apparatus at the first apparatus:
measuring a voice level of the first voice signal transmitted to the second apparatus at the second apparatus before the first voice signal is reproduced: and
adjusting the voice level of the first voice signal transmitted to the second apparatus in accordance with the measured voice level of the first voice signal to be transmitted and the measured voice level of the transmitted first voice signal.
6. The method according to claim 5, further comprising
measuring a voice level of the second voice in the vicinity of a position where the second voice is outputted; and
adjusting a voice level of the third voice signal in accordance with the measured voice level of the second voice.
7. A computer program product for enabling a computer to control a voice conference system including a first apparatus and a second apparatus connected to the first apparatus via a network, the computer program product comprising:
software instructions for enabling the computer to perform predetermined operations; and
a non-transitory computer readable medium bearing the software instructions,
the predetermined operations including:
collecting a first voice generated from a first voice source around the first apparatus and converting into a first voice signal;
transmitting the first voice signal to the second apparatus from the first apparatus;
reproducing the transmitted first voice signal by the second apparatus;
outputting the reproduced first voice signal as a second voice;
collecting the second voice and a third voice generated from a second voice source around the second apparatus as a second voice signal at the second apparatus;
separating the second voice signal into a third voice signal originated from the second voice and a fourth voice signal originated from the third voice;
transmitting the third voice signal to the first apparatus;
reproducing the transmitted third voice signal;
determining whether or not the first voice is normally reproduced by the second apparatus by comparing the first voice generated from the first voice source around the first apparatus with the reproduced third voice signal;
measuring a voice level of the first voice signal to be transmitted to the second apparatus at the first apparatus;
measuring a voice level of the first voice signal transmitted to the second apparatus at the second apparatus before the first voice signal is reproduced; and
adjusting the voice level of the first voice signal transmitted to the second apparatus in accordance with the measured voice level of the first voice signal to be transmitted and the measured voice level of the transmitted first voice signal.