Heterocyclyl compounds as MEK inhibitors

A compound of the general formula Ia, its tautomeric forms, its stereoisomers, its pharmaceutically acceptable salts, their combinations with suitable medicament and pharmaceutical compositions containing them,

• wherein:
• R1 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-alkynyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, and substituted- or unsubstituted-heterocyclyl;
• R3 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R4 is selected from the group consisting of hydrogen, halogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R6 and R7 are each independently selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
• or R6 and R7 are taken together with the nitrogen to which they are attached to form a substituted- or unsubstituted-heterocycle;
• Ra and Rb are independently selected from the group consisting of hydrogen, halogen and haloalkyl;
• Rc and Rd are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and substituted- or unsubstituted-alkyl, or Rc and Rd taken together with the carbon to which they are attached form a substituted- or unsubstituted-cycloalkyl;
• m is an integer selected from the group consisting of 1, 2, 3, and 4;
• when the alkyl group or alkenyl group is substituted, the alkyl group or alkenyl group is substituted with 1 to 4 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —OR10a, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10—N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the cycloalkyl group or cycloalkenyl group is substituted, the cycloalkyl group or cycloalkenyl group is substituted with 1 to 3 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, alkyl, alkenyl, perhaloalkyl, hydroxyalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the aryl group is substituted, the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heteroaryl group is substituted, the heteroaryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heterocyclyl group is substituted, the heterocyclyl group is substituted with 1 to 3 substituents,
• when the heterocyclic group is substituted on a ring carbon of the ‘heterocycle’, the substituents are independently selected from the group consisting of halogen, nitro, cyano, oxo, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, —OR10b, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10;
• when the heterocyclic group is substituted on a ring nitrogen of ‘heterocycle’, the substituents are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, —SO2R10a, —C(═O)R10a, C(═O)OR10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heterocyclic group is substituted on a ring sulphur of ‘heterocycle’, the sulfur is substituted with 1 or 2 oxo groups;
• R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• and
• R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl.

A compound of the general formula Ib, its tautomeric forms, its stereoisomers, its pharmaceutically acceptable salts, their combinations with suitable medicament and pharmaceutical compositions containing them,

• wherein:
• R1 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-alkynyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, and substituted- or unsubstituted-heterocyclyl;
• R3 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R4 is selected from the group consisting of hydrogen, halogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R8 and R9 are each independently selected from the group consisting of hydrogen, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl, or R8 and R9 taken together with the nitrogen to which they are attached form a substituted- or unsubstituted-heterocycle;
• with the provisos that both R8 and R9 cannot be hydrogen at the same time,
• and when R8 and R9 are not a part of heterocycle that is formed together with the nitrogen to which they are attached, at least one of the R8 and R9 is substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, or substituted- or unsubstituted-heterocyclyl;
• Ra and Rb are independently selected from the group consisting of hydrogen, halogen and haloalkyl;
• when the alkyl group or alkenyl group is substituted, the alkyl group or alkenyl group is substituted with 1 to 4 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —OR10a, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the cycloalkyl group or cycloalkenyl group is substituted, the cycloalkyl group or cycloalkenyl group is substituted with 1 to 3 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, alkyl, alkenyl, perhaloalkyl, hydroxyalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the aryl group is substituted, the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the heteroaryl group is substituted, the heteroaryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, O-perhaloalkyl,
• —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH— SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heterocyclyl group is substituted, the heterocyclyl group is substituted with 1 to 3 substituents,
• when the heterocyclic group is substituted on a ring carbon of the ‘heterocycle’, the substitutents are independently selected from the group consisting of halogen, nitro, cyano, oxo, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, —OR10b, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10;
• when the heterocyclic group is substituted on a ring nitrogen of the ‘heterocycle’, the substituents are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, —SO2R10a, —C(═O)R10a, C(═O)OR10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —NH— SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heterocyclic group is substituted on a ring sulphur of the ‘heterocycle’, is the sulfur substituted with 1 or 2 oxo groups;
• R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• and
• R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl.

A compound of the general formula Ic, its tautomeric forms, its stereoisomers, its pharmaceutically acceptable salts, their combinations with suitable medicament and pharmaceutical compositions containing them,

• wherein:
• R1 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-alkynyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, and substituted- or unsubstituted-heterocyclyl;
• R3 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R4 is selected from the group consisting of hydrogen, halogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
• R6 and R7 are each independently selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
• or R6 and R7 are taken together with the nitrogen to which they are attached to form a substituted- or unsubstituted-heterocycle;
• Ra and Rb are independently selected from the group consisting of hydrogen, halogen and haloalkyl;
• Rc and Rd are independently selected from the group consisting of hydrogen, halogen, hydroxyl, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl, or Rc and Rd taken together with the carbon to which they are attached form a substituted- or unsubstituted-cycloalkyl;
• m is an integer selected from the group consisting of 1, 2, 3, and 4;
• when the alkyl group or alkenyl group is substituted, the alkyl group or alkenyl group is substituted with 1 to 4 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —OR10a, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the cycloalkyl group or cycloalkenyl group is substituted, the cycloalkyl group or cycloalkenyl group is substituted with 1 to 3 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, alkyl, alkenyl, perhaloalkyl, hydroxyalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the aryl group is substituted, the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the heteroaryl group is substituted, the heteroaryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl, and —NH—SO2-cycloalkyl;
• when the heterocyclyl group is a substituted heterocyclyl group, the heterocyclyl group is substituted with 1 to 3 substituents,
• when the heterocyclic group is substituted on a ring carbon of the ‘heterocycle’, the substituents are independently selected from the group consisting of halogen, nitro, cyano, oxo, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, —OR10b, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10;
• when the heterocyclic group is substituted on a ring nitrogen of the ‘heterocycle’, the substituents are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, —SO2R10a, —C(═O)R10a, C(═O)OR10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl;
• when the heterocyclic group is substituted on a ring sulphur of ‘heterocycle’, the sulfur is substituted with 1 or 2 oxo groups;
• R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
• and
• R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl.

The compound selected from the group consisting of

• 3-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 1);
• N-cyclopropyl-3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 2);
• 1-(3-(azetidine-1-carbonyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound-3);
• N-cyclopropyl-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 4);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)-N-methylacetamide (Compound 5);
• N-cyclopropyl-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 6);
• 5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-1-(3-(morpholine-4-carbonyl)phenyl)pyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 7);
• 1-(3-(1,1-dioxidothiomorpholine-4-carbonyl)phenyl)-5-(2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 8);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-methylpropanamide (Compound 9);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N,N-dimethylacetamide (Compound 10);
• 2,2-difluoro-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,7,8-tetrahydropyrido[2,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 11);
• N-(1-carbamoylcyclopropyl)-3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 12);
• 3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide (Compound 13);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-hydroxyacetamide (Compound 14);
• 3-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N-methylpropanamide (Compound 15);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 16);
• 1-(3-(1,1-dioxidothiazolidine-3-carbonyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 17);
• 5-((2-fluoro-4-iodophenyl)amino)-1-(3-(4-hydroxypiperidine-1-carbonyl)phenyl)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 18);
• N-cyclopropyl-3-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 19);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)-2-methylpropanamide (Compound 20);
• 5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-1-(3-(4-methylpiperazine-1-carbonyl)phenyl)pyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 21);
• 5-((2-fluoro-4-iodophenyl)amino)-1-(3-(3-hydroxypyrrolidine-1-carbonyl)phenyl)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 22);
• 5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-1-(3-(piperazine-1-carbonyl)phenyl)pyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 23);
• 1-(3-(azetidine-1-carbonyl)phenyl)-3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 24);
• N-cyclopropyl-2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 25);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 26);
• 3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6, 8-dimethyl-1-(3-(pyrrolidine-1-carbonyl)phenyl)pyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 27);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-methylpropanamide (Compound 28);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N,N-dimethylacetamide (Compound 29);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,7, 8-tetrahydropyrido[2,3-d]pyrimidin-1(2H)-yl)phenyl)-2,2-difluoroacetamide (Compound 30);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N-(oxetan-3-yl)acetamide (Compound 31);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-hydroxyacetamide (Compound 32);
• 3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-1-(3-(2-(3-hydroxyazetidin-1-yl)-2-oxo ethyl)phenyl)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 33);
• 3-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 34);
• 2-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 35);
• 3-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N-methylpropanamide (Compound 36);
• N-cyclopropyl-3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 37);
• 3-cyclopropyl-1-(3-(1,1-dioxidothiazolidine-3-carbonyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 38);
• 3-cyclopropyl-1-(3-(1,1-dioxidothiomorpholine-4-carbonyl)phenyl)-5-((2-fluoro-4-iodo phenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 39);
• N-cyclopropyl-3-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 40);
• N-cyclopropyl-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 41);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 42);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetra hydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-methylpropanamide (Compound 43);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetra hydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N,N-dimethylacetamide (Compound 44);
• 2,2-difluoro-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 45);
• 1-(3-(2-(azetidin-1-yl)-2-oxoethyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 46);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetra hydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-hydroxyacetamide (Compound 47);
• 5-((2-fluoro-4-iodophenyl)amino)-1-(3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)phenyl)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 48);
• 3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)-N-(oxetan-3-yl)benzamide (Compound 49);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetra hydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N-(oxetan-3-yl)acetamide (Compound 50);
• 3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)-N-(tetrahydrofuran-3-yl)benzamide (Compound 51);
• 3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide (Compound 52);
• 3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)-N-(1-(hydroxymethyl)cyclopropyl)benzamide (Compound 53);
• N-cyclopropyl-3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 54);
• N-cyclopropyl-3-(5-((2-fluoro-4-iodophenyl)amino)-3-(2-hydroxyethyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 55);
• 1-(3-(azetidine-1-carbonyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 56);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 57);
• N-cyclopropyl-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 58);
• N-cyclopropyl-2-(3-(3-ethyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide (Compound 59);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)-N-methylacetamide (Compound 60);
• 3-(3-(3-ethyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 61);
• N-cyclopropyl-3-(3-ethyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 62);
• 5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-1-(3-(morpholine-4-carbonyl)phenyl)pyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 63);
• 1-(3-(1,1-dioxidothiomorpholine-4-carbonyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 65);
• 1-(3-(1,1-dioxidothiomorpholine-4-carbonyl)phenyl)-3-ethyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7(1H,3H,6H)-trione (Compound 66);
• 2-(3-(3-ethyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-N,N-dimethylacetamide (Compound 67);
• 3-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)propanamide (Compound 68);
• N-cyclopropyl-3-(5-((2-fluoro-4-iodophenyl)amino)-3-isopropyl-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 69);
• 2-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-3-(oxetan-3-yl)-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenoxy)acetamide (Compound 71);
• N-cyclopropyl-3-(3-(difluoromethyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 72);
• N-cyclopropyl-3-(3-(2,3-dihydroxypropyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)benzamide (Compound 73);
• 2-(1-(3-(cyclopropylcarbamoyl)phenyl)-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-1,2,6,7-tetrahydropyrido[4,3-d]pyrimidin-3(4H)-yl)acetic acid (Compound 74);
• (R)-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-hydroxyacetamide (Compound 75);
• (S)-2-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)-2-hydroxyacetamide (Compound 76);
• 1-(3-(5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido [4,3-d]pyrimidin-1(2H)-yl)phenyl) cyclopropanecarboxamide (Compound 77);
• 1-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetra hydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)cyclopropane carboxamide (Compound 78);
• and
• 1-(3-(5-((2-fluoro-4-iodophenyl)amino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro pyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)cyclopropanecarboxamide (Compound 79).