US 11,884,668 B1Granted

Substituted pyrido[3′,4′:4,5]pyrrolo[2,3-c]quinolines as CK2 inhibitors

AssigneeKing Faisal University

InventorsChristophe Tratrat, Michelyne Haroun

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Abstract

Pyrido[3′,4′:4,5]pyrrolo[2,3-c]quinolone compounds are provided. The pyrido[3′,4′:4,5]pyrrolo[2,3-c]quinolone compounds have the general formula: where R1 is H, C(O)OH4, O or OH: R2 is H, C(O)OH, C(O)OR4, or OH: and R3 is C—C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, (CH2)2-3NR7R8, (CH2)1-2aryl, (CH2)1-2heteroaryl, C(O)—(CH2)2-3NR7R8, C(O)aryl, C(O)heteroaryl, NH(CH2)2-3NR7R8, NH(CH2)0-1aryl, NH(CH2)0-1heteroaryl, NHC(O)—(CH2)2-3NR7R sNHC(O)aryl, NHC(O)heteroaryl, NHS(o)2-(CH2)2-3NR7R8, NHS(O)2aryl, NHS(O)2heteroaryl, S(O)2—(CH2)2-3NR7R8, S(O)2aryl, S(O)2heteroaryl, C3-C6 cycloalyl, C3-C6 halocycloalyl, C3-C6 cyanoccloalyl, aryl, or 5- or 6-membered heteroaryl. The compounds are inhibitors of protein kinase CK2 activity.

Claims11

Dependent claims

A compound having the formula I:

or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
R1 is H, C(O)OH, C(O)OR4, or OH;
R2 is H, C(O)OH, C(O)OR4, or OH;
R3 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, (CH2)2-3NR7R8, (CH2)1-2aryl, (CH2)1-2heteroaryl, C(O)—(CH2)2-3NR7R8, C(O)aryl, C(O)heteroaryl, NH(CH2)2-3NR7R8, NH(CH2)0-1aryl, NH(CH2)0-1heteroaryl, NHC(O)—(CH2)2-3NR7R8, NHC(O)aryl, NHC(O)heteroaryl, NHS(O)2—(CH2)2-3NR7R8, NHS(O)2aryl, NHS(O)2heteroaryl, S(O)2—(CH2)2-3NR7R8, S(O)2aryl, S(O)2heteroaryl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, aryl, or 5- or 6-membered heteroaryl;
wherein the aryl of (CH2)1-2aryl or the heteroaryl of (CH2)1-2heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NR5R6, C(O)OR5, NR5R6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
wherein the C(O)aryl, C(O)heteroaryl, aryl of NH(CH2)0-1aryl, heteroaryl of NH(CH2)0-1heteroaryl, aryl of NHC(O)aryl, heteroaryl of NHC(O)heteroaryl, aryl of NHS(O)2aryl, heteroaryl of NHS(O)2heteroaryl, S(O)2aryl, or S(O)2heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NRSR6, C(O)OR5, NRSR6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
and
wherein the aryl or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NRSR6, C(O)OR5, NRSR6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
each R4 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
each R5 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
each R6 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
or
any R5 and R6, taken together with the nitrogen atom to which they are attached, independently forms a nitrogen-containing heterocyclyl, wherein each nitrogen-containing heterocyclyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 trihaloalkyl, OH, and OC1-C6 alkyl;
each R7 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
and
each R8 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
or
any R7 and R8, taken together with the nitrogen atom to which they are attached, independently forms a nitrogen-containing heterocyclyl, wherein each nitrogen-containing heterocyclyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 trihaloalkyl, OH, and OC1-C6 alkyl.

16 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound having the formula I:

or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
R1 is H, C(O)OH, C(O)OR4, or OH;
R2 is H, C(O)OH, C(O)OR4, or OH;
R3 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, (CH2)2-3NR7R8, (CH2)1-2aryl, (CH2)1-2heteroaryl, C(O)—(CH2)2-3NR7R8, C(O)aryl, C(O)heteroaryl, NH(CH2)2-3NR7R8, NH(CH2)0-1aryl, NH(CH2)0-1heteroaryl, NHC(O)—(CH2)2-3NR7R8, NHC(O)aryl, NHC(O)heteroaryl, NHS(O)2—(CH2)2-3NR7R8, NHS(O)2aryl, NHS(O)2heteroaryl, S(O)2—(CH2)2-3NR7R8, S(O)2aryl, S(O)2heteroaryl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, aryl, or 5- or 6-membered heteroaryl;
wherein the aryl of (CH2)1-2aryl or the heteroaryl of (CH2)1-2heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NR5R6, C(O)OR5, NR5R6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
wherein the C(O)aryl, C(O)heteroaryl, aryl of NH(CH2)0-1aryl, heteroaryl of NH(CH2)0-1heteroaryl, aryl of NHC(O)aryl, heteroaryl of NHC(O)heteroaryl, aryl of NHS(O)2aryl, heteroaryl of NHS(O)2heteroaryl, S(O)2aryl, or S(O)2heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NRSR6, C(O)OR5, NRSR6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
and
wherein the aryl or 5- or 6-membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C(O)R5, C(O)NRSR6, C(O)OR5, NRSR6, NHC(O)R5, NHC(O)NHR5, NHC(O)OR5, NHS(O)2R5, NHS(O)2NHR5, OR5, S(O)2NR5R6, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, and C3-C6 cyanocycloalkyl;
each R4 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
each R5 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
each R6 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
or
any R5 and R6, taken together with the nitrogen atom to which they are attached, independently forms a nitrogen-containing heterocyclyl, wherein each nitrogen-containing heterocyclyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 trihaloalkyl, OH, and OC1-C6 alkyl;
each R7 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
and
each R8 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, or C3-C6 cyanocycloalkyl;
or
any R7 and R8, taken together with the nitrogen atom to which they are attached, independently forms a nitrogen-containing heterocyclyl, wherein each nitrogen-containing heterocyclyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 trihaloalkyl, OH, and OC1-C6 alkyl.

16 more elements