2-(2,4,5-substituted-anilino)pyrimidine compounds
The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.
1. A compound of Formula (II):
wherein:
G is 1H-indol-3-yl or 1-methyl-1H-indol-3-yl;
R 1 is hydrogen;
R 2 is methoxy; and
R 3 is [2-(dimethylamino)ethyl](methyl)amino or [2-(methylamino)ethyl](methyl)amino;
or a salt thereof.
2. A compound of Formula (II) or a salt thereof, as claimed in claim 1 , wherein R 3 is [2-(dimethylamino)ethyl](methyl)amino.
3. A compound of Formula (II) as claimed in claim 1 which is N 1 -(2-dimethylaminoethyl)-5-methoxy-N 1 -methyl-N 4 -[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine, or a salt thereof.
4. A compound of Formula (II) as claimed in claim 1 which is N 1 -(2-dimethylaminoethyl)-N 4 -[4-(1H-indol-3-yl)pyrimidin-2-yl]-5-methoxy-N 1 -methylbenzene-1,2,4-triamine, or a salt thereof.
5. A compound of Formula (III):
wherein:
G is 1H-indol-3-yl or 1-methyl-1H-indol-3-yl;
R 1 is hydrogen;
R 2 is methoxy; and
R 3 is [2-(dimethylamino)ethyl](methyl)amino or [2-(methylamino)ethyl](methyl)amino;
or a salt thereof.
6. A compound of Formula (III) or a salt thereof, as claimed in claim 5 wherein R 3 is [2-(dimethylamino)ethyl](methyl)amino.
7. A compound of Formula (III) as claimed in claim 5 , which is N′-(2-dimethylaminoethyl)-2-methoxy-N′-methyl-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]-5-nitrobenzene-1,4-diamine, or a salt thereof.
8. A compound of Formula (III) as claimed in claim 5 , which is N′-(2-dimethylaminoethyl)-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-2-methoxy-N′-methyl-5-nitrobenzene-1,4-diamine, or a salt thereof.
9. A compound of Formula (IV):
wherein:
G is 1H-indol-3-yl or 1-methyl-1H-indol-3-yl;
R 1 is hydrogen; and
R 2 is methoxy;
or a salt thereof.
10. A compound of Formula (IV) as claimed in claim 9 which is N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine, or a salt thereof.
11. A compound of Formula (IV) as claimed in claim 9 which is N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine, or a salt thereof.
12. A compound of Formula (VI):
wherein:
G is 1H-indol-3-yl or 1-methyl-1H-indol-3-yl;
R 1 is hydrogen;
R 2 is methoxy; and
R 3 is [2-(dimethylamino)ethyl](methyl)amino or [2-(methylamino)ethyl](methyl)amino;
or a salt thereof.
13. A compound of Formula (VI) or salt thereof, as claimed in claim 12 , wherein R 3 is [2-(dimethylamino)ethyl](methyl)amino.
14. A compound of Formula (VI) as claimed in claim 12 which is 3-chloro-N-[2-[2-dimethylaminoethyl-(methyl)amino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]-propanamide, or a salt thereof.