US 11,884,670 B1Granted

Pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one compounds as CK2 inhibitors

AssigneeKing Faisal University

InventorsChristophe Tratrat, Michelyne Haroun

Life of this patent

Estimating the term…

Abstract

Novel pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one compounds, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Claims15

Dependent claims

A compound having the formula I:

or a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof, wherein:
R is selected from the group consisting of —Ar, —NHAr, —NHCOAr, —NHSO2Ar, —NHCH2Ar, —NHCH2CH2NHR3, —NHCH2CH2NR3R4, —NHCH2CH2CH2NHR3, —NHCH2CH2CH2NR3R4, —NHCOCH2CH2NHR3, —NHCOCH2CH2NR3R4, —NHCOCH2CH2CH2NHR3, —NHCOCH2CH2CH2NR3R4, —NHSO2CH2CH2NHR3, —NHSO2CH2CH2NR3R4, —NHSO2CH2CH2CH2NHR3, —NHSO2CH2CH2CH2NR3R4, —CH2Ar, —COAr, —SO2Ar, —CH2CH2NHR3, —CH2CH2NR3R4, —CH2CH2CH2NHR3, —CH2CH2CH2NR3R4, —COCH2CH2NHR3, —COCH2CH2NR3R4, —COCH2CH2CH2NHR3, —COCH2CH2CH2NR3R4, —SO2CH2CH2NHR3, —SO2CH2CH2NR3R4, —SO2CH2CH2CH2NHR3, and —SO2CH2CH2CH2NR3R4;
Ar is an aryl ring or a 5 or 6 membered heteroaryl ring, either of the aryl ring or the heteroaryl ring being optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, —OH, —OR1, —NH2, —NHR1, —NR1R2, —CONH2, —CONHR1, —CONR1R2, —SO2NH2, —SO2NHR1, —SO2NR1R2, —NHCOR1, —NHCO2R1, —NHCONHR1, —NHSO2NHR1, —NHSO2R1, —COR1, —CO2R1, —CH2NHR1, —CH2NR1R2, —OCH2CO2R1, —OCH2CONHR1, —OCH2CONHR1R2, —OCH2COR1, —OCH2CONHR1, —OCH2CONR1R2, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched chain alkyl, and a cyano-C3-C6 cycloalkyl;
R1 and R2 are each independently selected from the group consisting of hydrogen, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched alkyl, and a cyano-C3-C6 cycloalkyl;
and
R3 and R4 are each independently selected from the group consisting of hydrogen, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched alkyl, and a cyano-C3-C6 cycloalkyl, or wherein R3 and R4, together with a nitrogen atom to which they are attached, form a nitrogen-containing heterocycle, such nitrogen-containing heterocycle being optionally substituted with from one to three substituents independently selected from the group consisting of a straight or branched C1-C6 alkyl group, a halogen atom, a straight or branched C1-C6 alkoxy group, a straight or branched C1-C6 trihaloalkyl group, and a hydroxy group.

3 more elements

A compound selected from the group consisting of:

5-((3-chlorophenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (1),
5-(m-tolylamino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (2),
5-((3-methoxyphenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (3),
5-((3-(dimethylamino)phenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (4),
N,N-dimethyl-3-((10-oxo-10,11-dihydro-9H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-5-yl)amino)benzamide (5),
N,N-dimethyl-3-((10-oxo-10,11-dihydro-9H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-5-yl)amino)benzenesulfonamide (6),
5-((3-isopropylphenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (7),
5-((4-chlorophenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (8),
5-(p-tolylamino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (9),
5-((4-methoxyphenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (10),
5-((4-(dimethylamino)phenyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (11),
5-((2-methylpyridin-4-yl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (12),
5-((3-chlorobenzyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (13),
5-((pyridin-3-ylmethyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (14),
5-((2-(dimethylamino)ethyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (15),
5-((2-(4-methylpiperazin-1-yl)ethyl)amino)-9,11-dihydro-10H-pyrido[4′,3′:4,5]pyrrolo[3,2-c][2,7]naphthyridin-10-one (16),
and a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof.

14 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

A compound having the formula I:

or a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof, wherein:
R is selected from the group consisting of —Ar, —NHAr, —NHCOAr, —NHSO2Ar, —NHCH2Ar, —NHCH2CH2NHR3, —NHCH2CH2NR3R4, —NHCH2CH2CH2NHR3, —NHCH2CH2CH2NR3R4, —NHCOCH2CH2NHR3, —NHCOCH2CH2NR3R4, —NHCOCH2CH2CH2NHR3, —NHCOCH2CH2CH2NR3R4, —NHSO2CH2CH2NHR3, —NHSO2CH2CH2NR3R4, —NHSO2CH2CH2CH2NHR3, —NHSO2CH2CH2CH2NR3R4, —CH2Ar, —COAr, —SO2Ar, —CH2CH2NHR3, —CH2CH2NR3R4, —CH2CH2CH2NHR3, —CH2CH2CH2NR3R4, —COCH2CH2NHR3, —COCH2CH2NR3R4, —COCH2CH2CH2NHR3, —COCH2CH2CH2NR3R4, —SO2CH2CH2NHR3, —SO2CH2CH2NR3R4, —SO2CH2CH2CH2NHR3, and —SO2CH2CH2CH2NR3R4;
Ar is an aryl ring or a 5 or 6 membered heteroaryl ring, either of the aryl ring or the heteroaryl ring being optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, —OH, —OR1, —NH2, —NHR1, —NR1R2, —CONH2, —CONHR1, —CONR1R2, —SO2NH2, —SO2NHR1, —SO2NR1R2, —NHCOR1, —NHCO2R1, —NHCONHR1, —NHSO2NHR1, —NHSO2R1, —COR1, —CO2R1, —CH2NHR1, —CH2NR1R2, —OCH2CO2R1, —OCH2CONHR1, —OCH2CONHR1R2, —OCH2COR1, —OCH2CONHR1, —OCH2CONR1R2, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched chain alkyl, and a cyano-C3-C6 cycloalkyl;
R1 and R2 are each independently selected from the group consisting of hydrogen, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched alkyl, and a cyano-C3-C6 cycloalkyl;
and
R3 and R4 are each independently selected from the group consisting of hydrogen, a C1-C6 straight chain alkyl, a C1-C6 branched alkyl, a C3-C6 cycloalkyl, a halo-C1-C6 straight chain alkyl, a halo-C1-C6 branched alkyl, a halo-C3-C6 cycloalkyl, a cyano-C1-C6 straight chain alkyl, a cyano-C1-C6 branched alkyl, and a cyano-C3-C6 cycloalkyl, or wherein R3 and R4, together with a nitrogen atom to which they are attached, form a nitrogen-containing heterocycle, such nitrogen-containing heterocycle being optionally substituted with from one to three substituents independently selected from the group consisting of a straight or branched C1-C6 alkyl group, a halogen atom, a straight or branched C1-C6 alkoxy group, a straight or branched C1-C6 trihaloalkyl group, and a hydroxy group.

3 more elements