CYCLIC AMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF DISEASE
The invention concerns compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein n, R 1 and R 2 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, novel intermediates useful in the preparation of such compounds, pharmaceutical compositions containing them and their use in the treatment of disease, for example cancer.
1 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
n is 1 or 2;
R 1 is selected from hydrogen, C 1-4 alkyl, C 1-3 alkoxyC 2-4 alkyl, hydroxyC 2-4 alkyl and
(R X )(R Y )N—C 2-4 alkyl, wherein R X and R Y each independently represent hydrogen or C 1-3 alkyl; and
R 2 is hydrogen, hydroxymethyl or 2-hydroxyethyl.
2 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1.
3 . A compound according to claim 1 or claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or C 1-4 alkyl.
4 . A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.
5 . A compound according to claim 1 selected from a group consisting of:
1-(4-{[2-Amino-4-(butylamino)-6-methylpyrimidin-5-yl]methyl}-3-methoxyphenyl)-4-methylpiperazin-2-one;
1-(4-{[2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl]methyl}-3-methoxyphenyl)-4-methylpiperazin-2-one;
(S)-1-(4-{[2-Amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl]methyl}-3-methoxyphenyl)-4-methylpiperazin-2-one;
(S)-1-(4-{[2-Amino-4-(1-hydroxypentan-2-ylamino)-6-methylpyrimidin-5-yl]methyl}-3-methoxyphenyl)-4-methylpiperazin-2-one;
(S)-1-(4-{[2-Amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl]methyl}-3-methoxyphenyl)piperazin-2-one;
or a pharmaceutically acceptable salt thereof.
6 . A pharmaceutical composition which comprises a compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.
7 . A compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof, for use as a medicament.
8 . A compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer.
9 . Use of a compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of cancer.
10 . A method of treating cancer in a warm blooded animal, such as man, in need of such treatment which comprises administering to said animal an effective amount of a compound of the Formula (I), or a pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 5 .
11 . A process for the preparation of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as defined in claim 1 , which comprises a step of reacting a compound of Formula (XXIII):
wherein R 1 is as defined in Formula (I) in claim 1 , and LG 4 is a leaving group;
with a compound of Formula (XII):
wherein R 2 and n are as defined in Formula (I) in claim 1 , in the presence or absence of a base.