US 9,056,832 B2Granted

Pyridine compounds and the users thereof

AssigneePurdue Pharma L.P.

InventorsChiyou Ni, Bin Shao, Laykea Tafesse, Jiangchao Yao, Jianming Yu, Xiaoming Zhou

Life of this patent

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Abstract

The invention relates to substituted pyridine compounds of Formula (I) and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein R1a, A1, A2, E, G, Z1, and Z2 are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

Claims14

Dependent claims

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) —O—;
b) —S—;
c) —SO—;
d) —SO2—
e) —NR4;
f) —SO2NH—;
and
g) —NHSO2—;
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 —(CH2CH2O)o—R15c;
R8a and R8b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
and
c) —(CH2CH2O)p—R15d;
L is —O—;
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) —SO2R24a;
d) —COR24b;
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.

107 more elements

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) —SO2R24a;
d) —COR 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.

24 more elements

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 ‘R)-1 ,1 ’-(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 ‘S)-1 ,1 ’-(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′,2′,3′,6′-tetrahydro-[4,4′-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-) ethyl]amino}-pyridine-2-carboxylic acid;
4-((S)-1,2-dihydroxy-ethyl)-6-(4′-fluoro-biphenyl-4-yl) pyridine-2-carboxylic acid amide;
4-((R)-1,2-dihydroxy-ethyl)-6-(4′-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′-fluoro-biphenyl-4-yl)pyridine-2-carboxylic acid amide;
4-((R)-1,2-dihydroxy-ethyl)-6[4-(4-trifluoromethoxy-phenoxy)phenyl]-pyridine-2-carboxylic acid amide;
6-((R)-1,2-dihydroxy-ethyl)-4-(4′-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.

164 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/821,732Filed 16 Sep 2011 · us provisional application
Priority: 17 Sep 2010
Published: US 2013/0303526 A114 Nov 2013
Granted: 16 Jun 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07D 213/81
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: amides; Imides
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 23/00
Anaesthetics

Family

Application61/384,136Us provisional application · filed 17 Sep 2010
US 2013/0303526 A1Pre-grant publication · published 14 Nov 2013
US 9,056,832 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

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) —O—;
b) —S—;
c) —SO—;
d) —SO2—
e) —NR4;
f) —SO2NH—;
and
g) —NHSO2—;
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 —(CH2CH2O)o—R15c;
R8a and R8b, which are identical or different, are selected from the group consisting of:
a) hydrogen;
b) unsubstituted alkyl;
and
c) —(CH2CH2O)p—R15d;
L is —O—;
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) —SO2R24a;
d) —COR24b;
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.

107 more elements

Facts

Application

13/821,732Filed 16 Sep 2011 · us provisional application

Priority

17 Sep 2010

Published

US 2013/0303526 A114 Nov 2013

Granted

16 Jun 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07D 213/81
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: amides; Imides
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 23/00
Anaesthetics