Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors
View Patent ↗This invention concerns N-(ortho phenylamino dihydropyridyl)sulfonamides and N-(ortho phenylamino dihydropyridyl), N′-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.
1. A compound of formula II or a pharmaceutically acceptable salt, or tautomer thereof:
wherein
B is H, C 1 -C 6 alkyl or C 2 -C 6 alkenyl;
wherein said C 1 -C 6 alkyl is optionally substituted with one or two groups selected independently from the group consisting of hydroxy, alkoxy, and oxy;
A and A′ are each independently H, C 1 -C 6 alkyl, or C 2 -C 6 alkenyl;
wherein each C 1 -C 6 alkyl is optionally substituted with one or two groups selected independently from the group consisting of hydroxy, alkoxy, and oxy; or
A and A′ together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group,
wherein each cyclopropyl, cyclobutyl, or cyclopentyl group is optionally substituted with one or two groups selected independently from the group consisting of methyl, hydroxy, and halogen;
X and Y are each independently halogen, methyl, SCH 3 or trifluoromethyl;
R 1 is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 5 -C 6 cycloalkenyl or C 2 -C 6 alkynyl;
wherein each of said alkyl, cycloalkyl, alkenyl, cycloalkenyl and alkynyl groups are optionally substituted with 1-3 substituents selected independently from the group consisting of halogen, hydroxy, C 1 -C 4 alky, C 1 -C 4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl difluoromethoxy and phenyl;
R 2 is H, halogen, hydroxy, azido, cyano, cyanomethyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 5 -C 6 cycloalkenyl or C 2 -C 6 alkynyl, wherein each of said alkyl, cycloalkyl, alkenyl cycloalkenyl and alkynyl groups are optionally substituted with 1-3 substituents selected independently from the group consisting of halogen, hydroxy, C 1 -C 4 alkoxy, cyano, cyanomethyl, nitro, azido, trifluoromethyl and phenyl; and
D is H or C 1 -C 4 alkyl.
2. The compound of claim 1 , where D is H or methyl.
3. The compound of claim 1 , where D is ethyl, n-propyl, or isopropyl.
4. The compound of claim 1 , where C(A)(A′)B is methyl or ethyl and D is methyl or ethyl.
5. The compound of claim 1 , where A and A′ together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group, wherein each cyclopropyl, cyclobutyl, or cyclopentyl group is optionally substituted with one or two groups selected independently from the group consisting of methyl, hydroxy, and halogen.
6. A compound which is
7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a compound of claim 6 and a pharmaceutically acceptable carrier.
9. A pharmaceutically acceptable salt of a compound of claim 1 .
10. A compound of claim 1 , or a pharmaceutically acceptable salt or tautomer thereof.
11. A compound which is
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising a compound of claim 9 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising a compound of claim 10 and a pharmaceutically acceptable carrier.