US 12,630,529 B2Granted

GCN2 modulator compounds

AssigneeAlesta Therapeutics BV

InventorsBalaji Dashrath Sathe, Brahmam Pujala, Gonzalo Andrés Ureta Díaz, Sebastian Bernales, Jennifer Borthwick

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Abstract

The disclosures herein relate to novel compounds of Formula (1): or a salt thereof, wherein X, Y, R1, R2, R3, R4 and R5 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with General Control Nondepressible 2 (GCN2).

Claims27

Dependent claims

A compound according to Formula (I):

or a salt thereof, wherein;
R1, R2, R3 and R4 are independently selected from the group consisting of H, halo and C1-3 alkyl optionally substituted with 1-6 fluoro, wherein at least one of R1, R2, R3, and R4is halo or C1-3 alkyl optionally substituted with 1-6 fluoro, or R4 is joined to R5 to form 5 or 6-membered heterocyclic ring, wherein the 5 or 6-membered heterocyclic ring is optionally substituted with halo and C1-3 alkyl optionally substituted with 1-6 fluoro;
R5 is selected from the group consisting of H and C1-3 alkyl optionally substituted with 1-6 fluoro;
X is a 9 or 10-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 9 or 10-membered fused heterobicyclic ring is substituted with NR8R9 and optionally further substituted with halo, C1-3 alkyl or NH2;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, —C(O)NH2, —C(O)—C1-6 alkyl, and 5 or 6-membered carbocyclic or heterocyclic ring, wherein the C1-6 alkyl, —C(O)—C1-6 alkyl, and 5 or 6-membered carbocyclic or heterocyclic ring are independently optionally substituted with 1-6 substituents selected from the group consisting halo, OH and phenyl,
or R8 and R9 taken together with the nitrogen form a 6-membered heterocyclic ring;
Y is a 5, 6, 9 or 10-membered carbocyclic or heterocyclic ring;
or NH2, wherein the 5, 6, 9 or 10-membered carbocyclic or heterocyclic ring is optionally substituted with 1-3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH;
R13 and R14 are independently H or C1-3 alkyl;
and
provided that
when X is a 9-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, then the 9 membered fused heterobicyclic ring is substituted with NR8R9 only, and Y is a 6-membered heterocyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 6-membered heterocyclic ring is optionally substituted with 1-3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH;
and
when X is a 10-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 10 membered fused heterobicyclic ring is substituted with NH2 only, one of R1, R2, R3 and R4 is halo or C1-3 alkyl, the remainder of R1, R2, R3 and R4 are H, R5 is H, and Y is 5 or 6-membered carbocyclic or heterocyclic ring, then the 5 or 6-membered carbocyclic or heterocyclic ring is substituted with 2 or 3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH.

11 more elements

A compound selected from the group consisting of:

N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-{3-[(2-aminopyrimidin-5-yl)ethynyl]-2,4-difluorophenyl}-5-chloro-2-
methoxypyridine-3-carboxamide
N-{3-[6-(2-aminopyrimidin-5-yl)pyridin-3-yl]-2,4-difluorophenyl}-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(2-aminoquinazolin-7-yl)-2,4-difluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-7-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
5-({3-[5-(5-chloro-2-methoxypyridin-3-yl)-1,3,4-oxadiazol-2-yl]-2,6-
difluorophenyl}ethynyl)pyrimidin-2-amine
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2,5-difluorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-3,4-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxybenzene-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2-methylphenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,6-difluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2-fluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-5-fluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2,4-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-4-methylphenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(4-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
2,5-dichloro-N-[2,4-difluoro-3-(7-fluoro-1H-benzimidazol-5-yl)phenyl]benzene-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-4-fluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinolin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(3-aminoisoquinolin-7-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminopyrido[2,3-d]pyrimidin-6-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(2-aminopyrido[3,2-d]pyrimidin-6-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(6-aminopyrido[2,3-b]pyrazin-2-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(7-aminopyrido[3,4-b]pyrazin-3-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(2-aminopteridin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinoxalin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(6-amino-9H-purin-8-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-amino-9H-purin-8-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(6-amino-9H-purin-2-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(8-amino-9H-purin-2-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
5-chloro-N-[2,4-difluoro-3-(7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl]-2-
methoxypyridine-3-sulfonamide
5-chloro-N-[2,4-difluoro-3-(7H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]-2-
methoxypyridine-3-sulfonamide
N-[3-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(2-amino-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(4-amino-7H-pyrrolo[3,2-d]pyrimidin-2-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(6-amino-7H-pyrrolo[3,2-d]pyrimidin-2-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
5-chloro-N-[2,4-difluoro-3-(1H-indazol-6-yl)phenyl]-2-methoxypyridine-3-sulfonamide
5-chloro-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]-2-methoxypyridine-3-
sulfonamide
N-[3-(2-amino-1H-pyrrolo[2,3-b]pyridin-6-yl)-2,4-difluorophenyl]-5-chloro-2-
methoxypyridine-3-sulfonamide
N-[3-(4-aminoquinazolin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(3-amino-1H-indazol-6-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
5-chloro-N-[3-(2,4-diaminoquinolin-6-yl)-2,4-difluorophenyl]-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-8-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-5-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
5-chloro-N-(2,4-difluoro-3-{2-[(2-hydroxyethyl)amino]quinazolin-6-yl}phenyl)-2-
methoxypyridine-3-sulfonamide
5-chloro-N-{2,4-difluoro-3-[2-(methylamino)quinazolin-6-yl]phenyl}-2-
methoxypyridine-3-sulfonamide
N-[3-(1H-benzimidazol-5-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-amino-1H-benzimidazol-5-yl)-2,4-difluorophenyl]-5-chloro-2-methoxypyridine-
3-sulfonamide
5-chloro-N-[2,4-difluoro-3-(7-fluoro-1H-benzimidazol-5-yl)phenyl]-2-methoxypyridine-
3-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2-methylphenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2-fluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-5-fluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,6-difluorophenyl]-5-chloro-2-methoxypyridine-3-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-5-chloro-2,4-difluorobenzene-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]sulfuric diamide
N-[3-(2-aminoquinazolin-6-yl)-4-fluorophenyl]-2,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-5-chloro-2-(trifluoromethyl)benzene-
1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-3,5-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2-chloro-5-methylbenzene-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-5-chloro-2-methylbenzene-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-2,3-dichlorobenzene-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-3-chloro-5-(trifluoromethyl)benzene-
1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]isoquinoline-5-sulfonamide
5-chloro-N-[2,4-difluoro-3-(2-{[(1r,4r)-4-hydroxycyclohexyl]amino}quinazolin-6-
yl)phenyl]-2-methoxypyridine-3-sulfonamide
5-chloro-N-[2,4-difluoro-3-(2-{[(2R)-1-hydroxypropan-2-yl]amino}quinazolin-6-
yl)phenyl]-2-methoxypyridine-3-sulfonamide
2,5-dichloro-N-[2,4-difluoro-3-(2-{[(1r,4r)-4-hydroxycyclohexyl]amino}quinazolin-6-
yl)phenyl]benzene-1-sulfonamide
2,5-dichloro-N-[2,4-difluoro-3-(2-{[(2R)-1-hydroxypropan-2-yl]amino}quinazolin-6-
yl)phenyl]benzene-1-sulfonamide
2,5-dichloro-N-[2,4-difluoro-3-(2-{[(1r,4r)-4-hydroxycyclohexyl]amino}quinazolin-6-
yl)phenyl]-3-(hydroxymethyl)benzene-1-sulfonamide
2,5-dichloro-N-[2,4-difluoro-3-(2-{[(2R)-1-hydroxypropan-2-yl]amino}quinazolin-6-
yl)phenyl]-3-(hydroxymethyl)benzene-1-sulfonamide
6-[1-(5-chloro-2-methoxypyridine-3-sulfonyl)-5-fluoro-1H-indol-4-yl]quinazolin-2-amine
6-[1-(5-chloro-2-methoxypyridine-3-sulfonyl)-1H-indol-4-yl]quinazolin-2-amine
6-[1-(5-chloro-2-methoxypyridine-3-sulfonyl)-5-fluoro-2,3-dihydro-1H-indol-4-
yl]quinazolin-2-amine
6-[1-(5-chloro-2-methoxypyridine-3-sulfonyl)-2,3-dihydro-1H-indol-4-yl]quinazolin-2-
amine
6-[1-(2,5-dichlorobenzene-1-sulfonyl)-5-fluoro-1H-indol-4-yl]quinazolin-2-amine
6-[1-(2,5-dichlorobenzene-1-sulfonyl)-1H-indol-4-yl]quinazolin-2-amine
{3-[4-(2-aminoquinazolin-6-yl)-5-fluoro-1H-indole-1-sulfonyl]-2,5-
dichlorophenyl}methanol
6-[1-(2,5-dichlorobenzene-1-sulfonyl)-5-fluoro-2,3-dihydro-1H-indol-4-yl]quinazolin-2-
amine
6-[1-(2,5-dichlorobenzene-1-sulfonyl)-2,3-dihydro-1H-indol-4-yl]quinazolin-2-amine
{3-[4-(2-aminoquinazolin-6-yl)-5-fluoro-2,3-dihydro-1H-indole-1-sulfonyl]-2,5-
dichlorophenyl}methanol
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]cyclohexanesulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]piperidine-4-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-1-methylpiperidine-4-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]piperidine-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]piperazine-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-methylpiperazine-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]oxane-4-sulfonamide
(1r,4r)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-hydroxycyclohexane-1-
sulfonamide
(1s,4s)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-hydroxycyclohexane-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]thiane-4-sulfonamide
(1r,4r)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-methoxycyclohexane-1-
sulfonamide
(1s,4s)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-methoxycyclohexane-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]morpholine-4-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-hydroxypiperidine-1-sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-(hydroxymethyl)piperidine-1-
sulfonamide
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]thiomorpholine-4-sulfonamide
(1r,4r)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-
(hydroxymethyl)cyclohexane-1-sulfonamide
(1s,4s)-N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-4-
(hydroxymethyl)cyclohexane-1-sulfonamide
3-{[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]sulfamoyl}cyclohexane-1-
carboxamide
3-{[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]sulfamoyl}cyclohexane-1-carboxylic
acid
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]piperidine-3-sulfonamide
3-{[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]sulfamoyl}-N-methylcyclohexane-1-
carboxamide
methyl 3-{[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]sulfamoyl}cyclohexane-1-
carboxylate
N-[3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl]-6-methylpiperidine-3-sulfonamide
N-(6-(3-((5-chloro-2-methoxypyridine)-3-sulfonamido)-2,6-difluorophenyl)quinazolin-2-
yl)pivalamide
N-(6-(3((2,5-dichlorophenyl)sulfonamido)2,6-difluorophenyl)quinazolin-2-yl)acetamide
N-(3-(2-aminoquinolin-6-yl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,5-dichloro-3-
(hydroxymethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-chloro-2,5-
dimethylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-5-fluoro-2-
methoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-5-yl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3,5-difluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3,5-dimethylbenzenesulfonamide
N-(5-(3-((5-chloro-2-methoxypyridine)-3-sulfonamido)-2,6-difluorophenyl)quinazolin-2-
yl)pivalamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3,4-dimethoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-fluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-methoxy-3-
methylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2-methoxy-5-
methylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,5-dimethoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-5-ethyl-2-
methoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,5-
bis(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)benzofuran-5-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-fluoro-5-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,3-difluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-methylbenzenesulfonamide
2,5-dichloro-N-(3,5-difluoro-4-(2-((2-hydroxyethyl)amino)quinazolin-6-yl)pyridin-2-
yl)benzenesulfonamide
5-chloro-N-(2,4-difluoro-3-(2-(((1s,4s)-4-hydroxycyclohexyl)amino)quinazolin-6-
yl)phenyl)-2-methoxypyridine-3-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)pyridine-3-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-dichlorophenyl)-5-chloro-2-methoxypyridine-3-
sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3,4-difluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-5-fluoro-2-
methylbenzenesulfonamide
2,5-dichloro-N-(2,4-difluoro-3-(2-((2-hydroxyethyl)amino)quinazolin-6-yl)phenyl)-3-
(hydroxymethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2-fluoro-5-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-fluoro-3-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-chloro-2-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)quinoxaline-5-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-
(trifluoromethoxy)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)thiophene-3-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-isopropylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)thiophene-2-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-fluoro-3-
methoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3,5-
bis(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-chloro-3-fluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-chloro-4-
methylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-chloro-4-
methoxybenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-chloro-3-
(trifluoromethyl)benzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,4,5-trichlorobenzenesulfonamide
5-chloro-N-(3-(2-((1,3-dihydroxypropan-2-yl)amino)quinazolin-6-yl)-2,4-
difluorophenyl)-2-methoxypyridine-3-sulfonamide
(R)-5-chloro-N-(2,4-difluoro-3-(2-((2-hydroxy-1-phenylethyl)amino)quinazolin-6-
yl)phenyl)-2-methoxypyridine-3-sulfonamide
5-chloro-N-(3-(2-(dimethylamino)quinazolin-6-yl)-2,4-difluorophenyl)-2-
methoxypyridine-3-sulfonamide
5-chloro-N-(2,4-difluoro-3-(2-(piperidin-1-yl)quinazolin-6-yl)phenyl)-2-
methoxypyridine-3-sulfonamide
(S)-5-chloro-N-(2,4-difluoro-3-(2-((1-hydroxypropan-2-yl)amino)quinazolin-6-
yl)phenyl)-2-methoxypyridine-3-sulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-chloro-4-fluorobenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-3-fluoro-4-
methylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-4-fluoro-3-
methylbenzenesulfonamide
N-(3-(2-aminoquinazolin-6-yl)-2,4-difluorophenyl)-2,3-dihydro-1H-indene-5-
sulfonamide
2,5-dichloro-N-(2,4-difluoro-3-(2-(methylamino)quinazolin-6-yl)phenyl)-3-
(hydroxymethyl)benzenesulfonamide
(S)-5-chloro-N-(2,4-difluoro-3-(2-((2-hydroxy-1-phenylethyl)amino)quinazolin-6-
yl)phenyl)-2-methoxypyridine-3-sulfonamide
5-chloro-N-(2,4-difluoro-3-(2-(((1r,4r)-4-hydroxycyclohexyl)amino)quinazolin-6-
yl)phenyl)-2-(trifluoromethyl)benzenesulfonamide
5-chloro-N-(2,4-difluoro-3-(2-(((1s,4s)-4-hydroxycyclohexyl)amino)quinazolin-6-
yl)phenyl)-2-(trifluoromethyl)benzenesulfonamide
(S)-5-chloro-N-(2,4-difluoro-3-(2-((2-hydroxy-1-phenylethyl)amino)quinazolin-6-
yl)phenyl)-2-(trifluoromethyl)benzenesulfonamide
(R)-5-chloro-N-(2,4-difluoro-3-(2-((2-hydroxy-1-phenylethyl)amino)quinazolin-6-
yl)phenyl)-2-(trifluoromethyl)benzenesulfonamide
2,5-dichloro-N-(2,4-difluoro-3-(2-((tetrahydrofuran-3-yl)amino)quinazolin-6-
yl)phenyl)benzenesulfonamide
or a salt thereof.

271 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/796,449Filed 17 Feb 2021
Priority: GB 200214417 Feb 2020
Published: US 2023/0143059 A111 May 2023
Granted: 19 May 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 35/00
Antineoplastic agents
C07D 235/14
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2: radicals substituted by nitrogen atoms

Family

US 2023/0143059 A1Pre-grant publication · published 11 May 2023
US 12,630,529 B2This patent

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

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Abstract

A compound according to Formula (I):

or a salt thereof, wherein;
R1, R2, R3 and R4 are independently selected from the group consisting of H, halo and C1-3 alkyl optionally substituted with 1-6 fluoro, wherein at least one of R1, R2, R3, and R4is halo or C1-3 alkyl optionally substituted with 1-6 fluoro, or R4 is joined to R5 to form 5 or 6-membered heterocyclic ring, wherein the 5 or 6-membered heterocyclic ring is optionally substituted with halo and C1-3 alkyl optionally substituted with 1-6 fluoro;
R5 is selected from the group consisting of H and C1-3 alkyl optionally substituted with 1-6 fluoro;
X is a 9 or 10-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 9 or 10-membered fused heterobicyclic ring is substituted with NR8R9 and optionally further substituted with halo, C1-3 alkyl or NH2;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, —C(O)NH2, —C(O)—C1-6 alkyl, and 5 or 6-membered carbocyclic or heterocyclic ring, wherein the C1-6 alkyl, —C(O)—C1-6 alkyl, and 5 or 6-membered carbocyclic or heterocyclic ring are independently optionally substituted with 1-6 substituents selected from the group consisting halo, OH and phenyl,
or R8 and R9 taken together with the nitrogen form a 6-membered heterocyclic ring;
Y is a 5, 6, 9 or 10-membered carbocyclic or heterocyclic ring;
or NH2, wherein the 5, 6, 9 or 10-membered carbocyclic or heterocyclic ring is optionally substituted with 1-3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH;
R13 and R14 are independently H or C1-3 alkyl;
and
provided that
when X is a 9-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, then the 9 membered fused heterobicyclic ring is substituted with NR8R9 only, and Y is a 6-membered heterocyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 6-membered heterocyclic ring is optionally substituted with 1-3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH;
and
when X is a 10-membered fused heterobicyclic ring comprising 1-4 annular heteroatoms being nitrogen, wherein the 10 membered fused heterobicyclic ring is substituted with NH2 only, one of R1, R2, R3 and R4 is halo or C1-3 alkyl, the remainder of R1, R2, R3 and R4 are H, R5 is H, and Y is 5 or 6-membered carbocyclic or heterocyclic ring, then the 5 or 6-membered carbocyclic or heterocyclic ring is substituted with 2 or 3 substituents selected from the group consisting of halo, OH, CN, —C(O)NR13R14, —NR13COR14, —C(O)OR13, C1-6 alkyl, C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted with 1-6 substituents selected from the group consisting of halo and OH.

11 more elements

Facts

Application

17/796,449Filed 17 Feb 2021

Priority

GB 200214417 Feb 2020

Published

US 2023/0143059 A111 May 2023

Granted

19 May 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 35/00
Antineoplastic agents
C07D 235/14
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2: radicals substituted by nitrogen atoms