Triazolyl aminopyrimidine compounds
The present invention provides triazolyl aminopyrimidine compounds useful in the treatment of cancer.
1. A compound of the formula:
wherein:
R 1 is hydrogen, methyl, cyclopropyl, cyclopropylamino(C 1 -C 2 alkyl), fluoro, ethoxy, hydroxy, 1-(hydroxy)ethyl, 2-(hydroxy)(C 2 -C 3 alkoxy), 2-(hydroxy)ethoxymethyl, 1-(chloro)ethyl, 1-((2-fluoro)ethylamino)ethyl, 2-(methylamino)ethoxy, (2-hydroxyethyl)amino, (2-hydroxyethyl)amino(C 1 -C 2 alkyl), amino, amino(C 1 -C 4 alkyl), amino(C 2 -C 3 alkoxy), aminocarbonylmethyl, (1-methyl)-(1-aminocarbonyl)ethyl, (C 1 -C 3 alkyl)amino(C 1 -C 2 alkyl), methoxyethylamino, N—(C 1 -C 3 alkyl)-N-methyl-amino(C 1 -C 2 alkyl), pyrrolidin-1-yl-methyl, 3-(dimethylamino)-pyrrolidin-1-yl-methyl, 3-(pyrid-3-yl)-pyrrolidin-1-yl-methyl, 3-(amino)pyrrolidin-1-yl-methyl, 3-(methylamino)pyrrolidin-1-yl-methyl, (4,4-dimethyloxalidin-3-yl)methyl, [N-(2-hydroxy)ethyl-N-methyl]-aminomethyl, (azetidin-1-yl)methyl, piperidin-1-yl-methyl, 4-(methoxy)piperidin-1-yl-methyl, 4-(hydroxy)piperidin-1-yl-methyl, 4-(hydroxymethyl)piperidin-1-yl-methyl, piperazin-1-yl-(C 1 -C 2 alkyl), 4-(methyl)piperazin-1-yl-methyl, 3,5-(dimethyl)piperazin-1-yl-methyl, or morpholin-4-yl-methyl;
R 2 is hydrogen;
R 3 is hydrogen, methyl, fluoro, or chloro, or R 3 is amino and together with R 2 forms a pyrrolyl ring fused to the pyridine;
R 4 is hydrogen, methyl, fluoro, or chloro;
R 5 is hydrogen or hydroxymethyl; and
R 6 is hydrogen or methyl; or
a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 wherein:
R 1 is cyclopropylamino(C 1 -C 2 alkyl), 1-(hydroxy)ethyl, 2-(hydroxy)ethoxymethyl, 1-(chloro)ethyl, 1-((2-fluoro)ethylamino)ethyl, (2-hydroxyethyl)amino, (2-hydroxyethyl)amino(C 1 -C 2 alkyl), amino(C 1 -C 4 alkyl), aminocarbonylmethyl, (1-methyl)-(1-aminocarbonyl)ethyl, (C 1 -C 3 alkyl)amino(C 1 -C 2 alkyl), N—(C 1 -C 3 alkyl)-N-methyl-amino(C 1 -C 2 alkyl), pyrrolidin-1-yl-methyl, 3-(dimethylamino)pyrrolidin-1-yl-methyl, 3-(pyrid-3-yl)-pyrrolidin-1-yl-methyl, 3-(amino)pyrrolidin-1-yl-methyl, 3-(methylamino)pyrrolidin-1-yl-methyl, (4,4-dimethyloxalidin-3-yl)methyl, [N-(2-hydroxy)ethyl-N-methyl]-aminomethyl, (azetidin-1-yl)methyl, piperidin-1-yl-methyl, 4-(methoxy)piperidin-1-yl-methyl, 4-(hydroxy)piperidin-1-yl-methyl, 4-(hydroxymethyl)piperidin-1-yl-methyl, piperazin-1-yl-(C 1 -C 2 alkyl), 4-(methyl)piperazin-1-yl-methyl, 3,5-(dimethyl)piperazin-1-yl-methyl, or morpholin-4-yl-methyl; or
a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 wherein:
R 1 is amino(C 1 -C 4 alkyl), (C 1 -C 3 alkyl)amino(C 1 -C 2 alkyl), N—(C 1 -C 3 alkyl)-N-methyl-amino(C 1 -C 2 alkyl), or morpholin-4-yl-methyl; or
a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 wherein:
R 1 is amino(C 1 -C 4 alkyl), or (C 1 -C 3 alkyl)amino(C 1 -C 2 alkyl);
R 3 is hydrogen or fluoro;
R 4 is hydrogen or fluoro;
R 5 is hydrogen; and
R 6 is hydrogen; or
a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 wherein R 1 is 1-(methylamino)ethyl, R 3 is fluoro and R 4 is hydrogen, R 5 is hydrogen, and R 6 is hydrogen, or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 wherein R 1 is 1-aminoethyl, R 3 is fluoro and R 4 is fluoro, R 5 is hydrogen, and R 6 is hydrogen, or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 wherein R 1 is 1-aminoethyl, R 3 is fluoro and R 4 is hydrogen, R 5 is hydrogen, and R 6 is hydrogen, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1 wherein R 1 is 1-(methylamino)ethyl, R 3 is fluoro and R 4 is fluoro, R 5 is hydrogen, and R 6 is hydrogen, or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.