Pyrimidine derivatives for the treatment of bacterial diseases
View Patent ↗The present invention relates to novel compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein the integers are as defined in the description. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.
1. A compound of formula I:
wherein:
Y represents:
none or one of N v , N w , N x , N y and N z (preferably one) represent(s) —N° and the others represent —C(H)═;
n represents 0 or 1;
X 1 represents —N—, X 2 is —C(H)—, and Q 1 represents a direct bond;
R z represents hydrogen or C 1-6 alkyl;
R x represents C 1-6 alkyl (optionally substituted by one or more substituents selected from A 1 ), aryl or heteroaryl (which latter two groups are each optionally substituted by one or more substituents selected from A 2 and A 3 , respectively);
R y , R y1 and R y2 independently represent hydrogen, halo, —CN, —OR 10 , —N(R 11 )(R 12 ) or C 1-6 alkyl (optionally substituted by one or more halo atoms);
A 1 , A 2 , A 3 and A 4 independently represent halo, —CN, —OR 1 , —S(O) 0-2 C 1-3 alkyl, C 1-6 alkyl (optionally substituted by one or more halo substituents), heterocycloalkyl (optionally substituted by one or more substituents selected from C 1-3 alkyl and halo), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from B 1 and B 2 , respectively);
each R 1 and R 10 independently represent hydrogen, C 1-6 alkyl (optionally substituted by one or more halo substituents), aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from halo, C 1-3 alkyl and —O—C 1-3 alkyl);
R 11 and R 12 independently represent hydrogen or C 1-6 alkyl;
B 1 and B 2 independently represent halo, —CN, C 1-6 alkyl (optionally substituted by one or more halo, —OH or —O—C 1-6 alkyl (optionally substituted by one or more halo atoms),
or a pharmaceutically acceptable salt thereof, with the proviso that the compound is not:
2. The compound according to claim 1 wherein:
R x represents C 1-6 alkyl (optionally substituted by one or more substituents selected from A 1 );
A 4 (which is preferably present on a carbon atom of the phenyl ring, and is preferably in the para-position) represents halo, —CN or —OC 1-3 alkyl;
A 1 represents halo, —CN, C 1-6 alkyl or —OR 1 ;
either all of R y , R y1 and R y2 represent hydrogen or, more preferably, at least one of R y , R y1 and R y2 (preferably R y ) represents a substituent other than hydrogen and the others (preferably R y1 and R y2 ) represents hydrogen (i.e. there is preferably one substituent present on the phenyl ring, preferably in the meta-position);
when R y is other than hydrogen, it preferably represents halo, —OCH 3 or —CN; and/or
R 1 represents hydrogen.
3. The compound according to claim 1 wherein the compound is:
or a pharmaceutically acceptable salt thereof.
4. A combination of (a) a compound as defined in claim 1 , and (b) one or more other antibacterial agents.