Heteroaryl-substituted arylaminopyridine derivatives as MEK inhibitors

A compound of Formula (II),

• as well as tautomers and pharmaceutically acceptable thereof, wherein:
• Y is either NR′ or O;
• R1 is selected from hydrogen, C1-C6-alkyl, OR6, NR7R8, SR6, NR7S(O)(O)R′, NR7C(O)R6, NR7C(O)NR7R6, or NR7C(O)OR6;
• R2 is halogen;
• R3 is selected from Cl, F or I;
• R4 and R5 are independently selected from hydrogen, halogen, C1-C6 alkyl or C1-C6 alkoxy, wherein said alkyl or alkoxy is substituted or unsubstituted;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′ or C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted.

A compound of Formula (IIa) or Formula (IIb),

• as well as tautomers and pharmaceutically acceptable salts thereof, wherein:
• R1 is selected from hydrogen, trimethylsilyl, C1-C6-alkyl, OR6, C(O)OR6, NR7R8, SR6, NR7S(O)(O)R′, NR7C(O)R6, NR7C(O)NR7R6, NR7C(O)OR6, NR7C(O)C(O)OR6, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl or C1-C4 alkyl-(OR′)n;
• R2 is selected from halogen, C1-C6-alkyl or OR6;
• R3 is halogen, trimethylsilyl, C1-C6-alkyl or OR6;
• R4 and R5 are independently selected from hydrogen, halogen, C1-C6 alkyl or C1-C6 alkoxy, wherein said alkyl or alkoxy is substituted or unsubstituted;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl, C1-C4 alkyl-(OR′)n or C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, and alkyl-heterocycloalkyl is substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted;
• or
• R′ and R″ can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• n is 0 to 2.

A compound of Formula (III)

• as well as tautomers and pharmaceutically acceptable salts thereof, wherein:
• Y is either O, or NR';
• R1 is selected from hydrogen, C1-C6-alkyl, OR6, NR7R8 or SR6 or NR7S(O)(O)R′;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, or heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′, C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10 membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted.

A compound of Formula (IIIa) or Formula (IIIb)

• as well as tautomers and pharmaceutically acceptable salts thereof, wherein:
• R1 is selected from hydrogen, trimethylsilyl, C1-C6-alkyl, OR6, C(O)OR6, NR7R8, SR6, NR7S(O)(O)R′, NR7C(O)R6, NR7C(O)NR7R6, NR7C(O)OR6, NR7C(O)C(O)OR6, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl or C1-C4 alkyl-(OR′)n;
• R4 and R5 are independently selected from hydrogen, halogen, C1-C6 alkyl or C1-C6 alkoxy, wherein said alkyl or alkoxy is substituted or unsubstituted;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl, C1-C4 alkyl-(OR′)n or C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, and alkyl-heterocycloalkyl is substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted;
• or
• R′ and R″ can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• n is 0 to 2.

A compound of Formulae (IVa) or (IVb)

• as well as tautomers and pharmaceutically acceptable salts thereof, wherein:
• R1 is selected from hydrogen, C1-C6-alkyl, OR6, NR7R8 or SR6 or NR7S(O)(O)R′;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′ or C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted.

A compound of Formulae (IVa) or (IVb)

• as well as tautomers and pharmaceutically acceptable salts thereof, wherein:
• R1 is selected from hydrogen, trimethylsilyl, C1-C6-alkyl, OR6, C(O)OR6, NR7R8, SR6, NR7S(O)(O)R′, NR7C(O)R6, NR7C(O)NR7R6, NR7C(O)OR6, NR7C(O)C(O)OR6, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl or C1-C4 alkyl-(OR′)n;
• R6, R7 and R8 are independently selected from hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, C1-C4 alkyl-C(O)OR′, C1-C4 alkyl-OR′, C1-C4-alkyl-NR′R″, C1-C4-alkyl-heterocycloalkyl, C1-C4 alkyl-(OR′)n or C1-C4 alkyl-C(O)NR′R″, wherein said alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, and alkyl-heterocycloalkyl is substituted or unsubstituted;
• or
• R7 and R8 can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• R′ and R″ are independently selected from hydrogen, C1-C6-alkyl or aryl, wherein said alkyl or aryl is substituted or unsubstituted;
• or
• R′ and R″ can be taken together with the atom to which they are attached to form a 4 to 10-membered heteroaryl or heterocyclic ring, each of which is substituted or unsubstituted;
• and
• n is 0 to 2.