US 2014/0005212 A1Published application

Substituted Pyridines as Sodium Channel Blockers

AssigneePurdue Pharma L.P.

InventorsChiyou Ni, Minnie Park, Bin Shao, Laykea Tafesse, Jiangchao Yao, Mark Youngman, Xiaoming Zhou

Life of this patent

Estimating the term…

Abstract

The invention relates to substituted pyridine compounds of Formula I: (I) and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein R1a, R1b, R2a, R2b, R2c, A1, A2, and X 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.

Claims38

Dependent claims

A compound having Formula I:

wherein:
A1 is selected from the group consisting of:
a) optionally substituted cycloalkyl;
b) optionally substituted heterocyclo;
e) optionally substituted aryl;
and
d) optionally substituted heteroaryl;
X is selected from the group consisting of:
a) —O—;
b) —S—;
c) —SO—;
d) —SO2—
e) —(CR3R4)m—;
f) —NR5—;
g) —SO2NH—;
and
h) —NHSO2—;
wherein:
each R3 and R4, which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) halo;
and
c) optionally substituted alkyl;
or
each R3 and R4 taken together with the carbon atom to which they are attached form a 3- to 8-membered optionally substituted cycloalkyl or optionally substituted heterocyclo;
m is 0, 1, 2, or 3;
and
R5 is selected from the group consisting of hydrogen and optionally substituted alkyl;
A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl;
R1a is selected from the group consisting of:
a) optionally substituted alkyl;
b) (heterocyclo)alkyl;
c) (heteroaryl)alkyl;
d) (amino)alkyl;
e) (alkylamino)alkyl;
f) (dialkylamino)alkyl;
g) (carboxamido)alkyl;
h) (cyano)alkyl;
i) alkoxyalkyl;
j) hydroxyalkyl;
k) heteroalkyl
l) optionally substituted heterocyclo;
m) —SO2R6;
and
n) —COR7;
wherein:
R6 is selected from the group consisting of:
a) optionally substituted alkyl;
b) optionally substituted cycloalkyl;
c) optionally substituted aryl;
d) optionally substituted heteroaryl;
e) amino;
f) alkylamino;
g) dialkylamino;
h) cycloalkylamino;
i) heterocycloalkylamino;
j) heteroarylamino;
k) arylamino;
and
l) optionally substituted alkenyl;
R7 is selected from the group consisting of:
a) optionally substituted heteroaryl;
b)
and
c) hydroxyalkyl;
wherein:
p is 0, 1, or 2;
each R8a and R8b which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) aralkyl;
d) (heterocyclo)alkyl;
e) (heteroaryl)alkyl;
f) (amino)alkyl;
g) (alkylamino)alkyl;
h) (dialkylamino)alkyl;
i) (carboxamido)alkyl;
j) (cyano)alkyl;
k) alkoxyalkyl;
l) hydroxyalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
and
q) carboxamido;
R9a is selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) —COR10;
d) —SO2R11;
and
e) R25;
wherein:
R10 is selected from the group consisting of:
a) optionally substituted alkyl;
b) aralkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
k) hydroxyalkyl;
l) heteroalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
q) amino;
r) alkylamino;
s) dialkylamino;
t) cycloalkylamino;
u) heterocycloalkylamino;
v) heteroarylamino;
w) arylamino;
x) alkoxy;
and
y) haloalkyl
R11 is selected from the group consisting of:
a) optionally substituted alkyl;
b) aralkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
k) hydroxyalkyl;
l) heteroalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
q) amino;
r) alkylamino;
s) dialkylamino;
t) cycloalkylamino;
u) heterocycloalkylamino;
v) heteroarylamino;
and
w) arylamino;
R9b is selected from the group consisting of hydrogen and optionally substituted alkyl;
or
R9a and R9b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
R1b selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
and
j) hydroxyalkyl;
or
R1a and R1b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
R2a, R2b, and R2c, which can be 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) optionally substituted alkyl
aa) (amino)alkyl;
and
bb) (diamino)alkyl;
and
R25 is:
R8c and R8d, which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) aralkyl;
d) (heterocyclo)alkyl;
e) (heteroaryl)alkyl;
f) (amino)alkyl;
g) (alkylamino)alkyl;
h) (dialkylamino)alkyl;
i) (carboxamido)alkyl;
j) (cyano)alkyl;
k) alkoxyalkyl;
l) hydroxyalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
and
p) optionally substituted heteroaryl;
and
R26 is selected from the group consisting of:
a) hydroxy;
b) alkoxy;
c) amino;
d) alkylamino;
e) dialkylamino;
f) hydroxyalkylamino;
g) arylamino;
and
h) cycloalkylamino,
or a pharmaceutically acceptable salt or solvate thereof,
with the proviso:
when R7 is optionally substituted heteroaryl, then A1 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl.

225 more elements

A compound selected from the group consisting of:

(S)-2-acetamido-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-4-methylpentanamide;
(S)-2-acetamido-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-phenylpropanamide;
(S)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-4-methyl-1-oxopentan-2-yl)picolinamide;
(S)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-4-methyl-1-oxopentan-2-yl)cyclopropanecarboxamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(2-(2-methoxyethoxy)acetamido)-4-methylpentanamide;
(S)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-4-methyl-1-oxopentan-2-yl)nicotinamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(3-isopropylureido)-4-methylpentanamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-4-methyl-2-ureidopentanamide;
N-(4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanesulfonamide;
(S)—N-(4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-N-(2,3-dihydroxypropyl)methanesulfonamide;
N-(4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)sulfamide;
(S)—N-(4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl) methanesulfonamide;
(S)—N-(4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanesulfonamide;
N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)cyclopropanesulfonamide;
N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-1-methyl-1H-imidazole-4-sulfonamide;
(S)-2-amino-N-(6 (4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1H-imidazol-4-yl)propanamide;
(S)-2-acetamido-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1H-imidazol-4-yl)propanamide;
(S)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)cyclopropanecarboxamide;
(S)-1-acetyl-N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)piperidine-4-carboxamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1H-imidazol-4-yl)-2-(2-methoxyacetamido)propanamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(2-hydroxyacetamido)-3-(1H-imidazol-4-yl)propanamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(2-hydroxy-2-methylpropanamido)-3-(1H-imidazol-4-yl)propanamide;
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1H-imidazol-4-yl)-2-(methylsulfonamido)propanamine;
(S)-tert-butyl(1-amino-4-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-1,4-dioxobutan-2-yl)carbamate;
(S)-tert-butyl(4-amino-1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-1,4-dioxobutan-2-yl)carbamate;
N—((S)-1-((4-((S)-1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-4-methyl-1-oxopentan-2-yl)cyclopropanecarboxamide;
N—((S)-1-((4-((S)-1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-4-methyl-1-oxopentan-2-yl)picolinamide;
2-(4-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)piperidin-1-yl)acetic acid;
1-(4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)piperidine-4-carboxylic acid;
(2S,4R)-1-(3-chloro-5-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-4-hydroxypyrrolidine-2-carboxylic acid;
(2S,4R)-1-(4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-4-hydroxypyrrolidine-2-carboxylic acid;
1-(2-((4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)ethyl)imidazolidin-2-one;
2-amino-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-6-hydroxypyrimidine-4-carboxamide;
(S)-1-(2-((4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)ethyl)imidazolidin-2-one,
pyridine-2-carboxylic acid ((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-amide,
cyclopropanecarboxylic acid ((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-amide,
N—((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-nicotinamide,
N—((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-isonicotinamide,
5-methyl-isoxazole-3-carboxylic acid ((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-amide,
((S)-1-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-hydroxy-ethyl)-carbamic acid tert-butyl ester,
(S)—N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-yl}-3-hydroxy-2-(2-hydroxy-acetylamino)-propionamide,
(S)—N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-yl}-3-hydroxy-2-ureido-propionamide,
((S)—-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-ylcarbamoyl}-2-pyridin-3-yl-ethyl)-carbamic acid tert-butyl ester,
(S)-2-acetylamino-N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-yl}-3-pyridin-3-yl-propionamide,
(S)-2-acetylamino-N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-yl}-3-hydroxy-butyramide,
(S)-2-amino-N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pridin-2-yl}-3-hydroxy-propionamide, and
(S)-2-amino-N-{6-[4-(4-fluoro-phenoxy)-phenyl]-pyridin-2-yl}-3-pyridin-3-yl-propionamide,
or a pharmaceutically acceptable salt or solvate thereof.

46 more elements

A compound selected from the group consisting of:

N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2,3-dihydroxypropanamide,
N-(6-(4-(4-cyanophenoxy)phenyl)pyridin-2-yl)-2,3-dihydroxypropanamide,
N-(6-O-(3-cyano-4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)-2,3-dihydroxypropanamide,
N-(6-(4-(4-cyano-3-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl)-2,3-dihydroxypropanamide,
2,3-dihydroxy-N-(6-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-yl) propanamide,
(S)-2-acetamido-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1-methyl-1H-imidazol-4-yl)propanamide,
(R)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(2-hydroxy-2-methylpropanamido)-3-(1-methyl-1H-imidazol-4-yl)propanamide,
(S)-2-((4-chloro-6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino) propanamide,
(S)-2-((1-amino-1-oxopropan-2-yl)amino)-6-(4-(4-fluorophenoxy)phenyl) isonicotinamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1-methyl-1H-imidazol-4-yl)-2-propionamidopropanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-isobutyramido-3-(1 methyl-1H-imidazol-4-yl)propanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1-methyl-1H-imidazol-4-yl)-2-pivalamidopropanamide,
(S)-2-acetamido-N-(4-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1-methyl-1H-imidazol-4-yl)propanamide,
(S)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-3-(1-methyl-1H-imidazol-4-yl)-1-oxopropan-2-yl)cyclopropanecarboxamide,
(S)-3,3,3-trifluoro-N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-3-(1-methyl-1H-imidazol-4-yl)-1-oxopropan-2-yl)propanamide,
(S)-2-acetamido-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-(1-methyl-1H-imidazol-5-yl)propanamide,
(R)—N-(1-((6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)amino)-3-(1-methyl-1H-imidazol-4-yl)-1-oxopropan-2-yl)-4-(trifluoromethyl)benzamide,
(S)-2-(3-(tert-butyl)ureido)-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-hydroxypropanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-(2-hydroxyacetamido)-4-methylpentanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-hydroxy-2-(3-isopropylureido)propanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-hydroxy-2-(2-hydroxy-2-methylpropanamido)propanamide,
(S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-hydroxy-2-(2-methoxyacetamido)propanamide,
(R)-2-acetamido-3-(1-methyl-1H-imidazol-4-yl)-N-(6-(4-((5-(trifluoromethyl) pyridin-2-yl)oxy)phenyl)pyridin-2-yl)propanamide,
(2S,3S)—N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-3-hydroxy-2-(2-hydroxyacetamido)butanamide,
2,3-dihydroxy-N-(6-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)pyridin-2-yl)propanamide,
(E)-N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2-phenylethene sulfonamide,
N-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-6-carboxamide,
(S)-2-(3-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ureido)-3-(1-methyl-1H-imidazol-4-yl)propanamide,
(S)-methyl 2-(3-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ureido)-3-(1-methyl-1H-imidazol-4-yl)propanoate,
(R)-2-(3-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ureido)-3-(1H-indol-2-yl) propanamide,
(R)-2-(3-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ureido)succinamide, and
(R)-2-(3-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)ureido)-3-(1H-imidazol-5-yl)propanamide,
or a pharmaceutically acceptable salt or solvate thereof.

30 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/996,082Filed 21 Dec 2011
Priority: 22 Dec 2010
Published: 2 Jan 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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 23/02
Anaesthetics: local anaesthetics

Family

Application61/426,318Us provisional application · filed 22 Dec 2010
US 9,656,959 B2Related patent
US 2014/0005212 A1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound having Formula I:

wherein:
A1 is selected from the group consisting of:
a) optionally substituted cycloalkyl;
b) optionally substituted heterocyclo;
e) optionally substituted aryl;
and
d) optionally substituted heteroaryl;
X is selected from the group consisting of:
a) —O—;
b) —S—;
c) —SO—;
d) —SO2—
e) —(CR3R4)m—;
f) —NR5—;
g) —SO2NH—;
and
h) —NHSO2—;
wherein:
each R3 and R4, which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) halo;
and
c) optionally substituted alkyl;
or
each R3 and R4 taken together with the carbon atom to which they are attached form a 3- to 8-membered optionally substituted cycloalkyl or optionally substituted heterocyclo;
m is 0, 1, 2, or 3;
and
R5 is selected from the group consisting of hydrogen and optionally substituted alkyl;
A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl;
R1a is selected from the group consisting of:
a) optionally substituted alkyl;
b) (heterocyclo)alkyl;
c) (heteroaryl)alkyl;
d) (amino)alkyl;
e) (alkylamino)alkyl;
f) (dialkylamino)alkyl;
g) (carboxamido)alkyl;
h) (cyano)alkyl;
i) alkoxyalkyl;
j) hydroxyalkyl;
k) heteroalkyl
l) optionally substituted heterocyclo;
m) —SO2R6;
and
n) —COR7;
wherein:
R6 is selected from the group consisting of:
a) optionally substituted alkyl;
b) optionally substituted cycloalkyl;
c) optionally substituted aryl;
d) optionally substituted heteroaryl;
e) amino;
f) alkylamino;
g) dialkylamino;
h) cycloalkylamino;
i) heterocycloalkylamino;
j) heteroarylamino;
k) arylamino;
and
l) optionally substituted alkenyl;
R7 is selected from the group consisting of:
a) optionally substituted heteroaryl;
b)
and
c) hydroxyalkyl;
wherein:
p is 0, 1, or 2;
each R8a and R8b which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) aralkyl;
d) (heterocyclo)alkyl;
e) (heteroaryl)alkyl;
f) (amino)alkyl;
g) (alkylamino)alkyl;
h) (dialkylamino)alkyl;
i) (carboxamido)alkyl;
j) (cyano)alkyl;
k) alkoxyalkyl;
l) hydroxyalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
and
q) carboxamido;
R9a is selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) —COR10;
d) —SO2R11;
and
e) R25;
wherein:
R10 is selected from the group consisting of:
a) optionally substituted alkyl;
b) aralkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
k) hydroxyalkyl;
l) heteroalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
q) amino;
r) alkylamino;
s) dialkylamino;
t) cycloalkylamino;
u) heterocycloalkylamino;
v) heteroarylamino;
w) arylamino;
x) alkoxy;
and
y) haloalkyl
R11 is selected from the group consisting of:
a) optionally substituted alkyl;
b) aralkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
k) hydroxyalkyl;
l) heteroalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
p) optionally substituted heteroaryl;
q) amino;
r) alkylamino;
s) dialkylamino;
t) cycloalkylamino;
u) heterocycloalkylamino;
v) heteroarylamino;
and
w) arylamino;
R9b is selected from the group consisting of hydrogen and optionally substituted alkyl;
or
R9a and R9b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
R1b selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) (heterocyclo)alkyl;
d) (heteroaryl)alkyl;
e) (amino)alkyl;
f) (alkylamino)alkyl;
g) (dialkylamino)alkyl;
h) (carboxamido)alkyl;
i) (cyano)alkyl;
j) alkoxyalkyl;
and
j) hydroxyalkyl;
or
R1a and R1b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
R2a, R2b, and R2c, which can be 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) optionally substituted alkyl
aa) (amino)alkyl;
and
bb) (diamino)alkyl;
and
R25 is:
R8c and R8d, which can be identical or different, are selected from the group consisting of:
a) hydrogen;
b) optionally substituted alkyl;
c) aralkyl;
d) (heterocyclo)alkyl;
e) (heteroaryl)alkyl;
f) (amino)alkyl;
g) (alkylamino)alkyl;
h) (dialkylamino)alkyl;
i) (carboxamido)alkyl;
j) (cyano)alkyl;
k) alkoxyalkyl;
l) hydroxyalkyl;
m) optionally substituted cycloalkyl;
n) optionally substituted aryl;
o) optionally substituted heterocyclo;
and
p) optionally substituted heteroaryl;
and
R26 is selected from the group consisting of:
a) hydroxy;
b) alkoxy;
c) amino;
d) alkylamino;
e) dialkylamino;
f) hydroxyalkylamino;
g) arylamino;
and
h) cycloalkylamino,
or a pharmaceutically acceptable salt or solvate thereof,
with the proviso:
when R7 is optionally substituted heteroaryl, then A1 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl.

225 more elements

Facts

Application

13/996,082Filed 21 Dec 2011

Priority

22 Dec 2010

Published

2 Jan 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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 23/02
Anaesthetics: local anaesthetics