Difluoromethyl-aminopyridines and difluoromethyl-aminopyrimidines

1. A compound of formula (I),

wherein

X 1 and X 3 are N, and

X 2 is CH;

Y is N or CH;

R 1 and R 2 are independently of each other

(i) a morpholinyl of formula (II)

wherein the arrow denotes the bond in formula (I); and

wherein R 3 and R 4 are independently of each other H, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, CN, or C(O)O—C 1 -C 2 alkyl; or R 3 and R 4 form together a bivalent residue —R 5 R 6 — selected from C 1 -C 3 alkylene optionally substituted with 1 to 4 F, —CH 2 —O—CH 2 —, —CH 2 —NH—CH 2 —, or any of the structures

wherein the arrows denote the bonds in formula (II);

(ii) phenyl optionally substituted with 1 to 3 R 7 , wherein R 7 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 ) 2 ;

(iii) a 5- to 6-membered heteroaryl ring W containing one to four heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 8 , wherein R 8 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 ) 2 ;

(iv) a saturated 4- to 6-membered heterocyclic ring Z containing 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 9 ; wherein R 9 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, ═O, —NH 2 , NHCH 3 or N(CH 3 ) 2 ; or two R 9 substituents form together a bivalent residue —R 10 R 11 — selected from C 1 -C 3 alkylene optionally substituted with 1 to 4 F, —CH 2 —O—CH 2 — or —O—CH 2 CH 2 —O—;

(v) OR 12 , wherein R 12 is C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 3 -C 6 cycloalkyl, C 1 -C 2 alkyleneC 3 -C 6 cycloalkyl; Cycle-P or C 1 -C 2 alkyleneCycle-P, wherein Cycle-P represents a saturated 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 13 , wherein R 13 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 ); Cycle-Q or C 1 -C 2 alkyleneCycle-Q, wherein Cycle-Q represents 5- to 6-membered heteroaryl ring containing one to four heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 14 , wherein R 14 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 ); or

(vi) NR 15 R 16 ; wherein R 15 and R 16 are independently of each other H, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl; Cycle-P or C 1 -C 2 alkyleneCycle-P, wherein Cycle-P represents a saturated 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 13 , wherein R 13 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 ); Cycle-Q or C 1 -C 2 alkyleneCycle-Q, wherein Cycle-Q represents 5- to 6-membered heteroaryl ring containing one to four heteroatoms independently selected from N, O and S, optionally substituted by 1 to 3 R 14 , wherein R 14 is independently at each occurrence halogen, —OH, C 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy, C 1 -C 2 alkoxyC 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, —NH 2 , NHCH 3 or N(CH 3 );

with the proviso that at least one of R 1 and R 2 is a morpholinyl of formula II;

or a tautomer, solvate, or a pharmaceutically acceptable salt thereof.

2. The compound of formula (I) according to claim 1 , wherein said R 1 and said R 2 are independently of each other (i) a morpholinyl of formula (II); (ii) said 5- to 6-membered heteroaryl ring W; (iii) said saturated 4- to 6-membered heterocyclic ring Z; (iv) said OR 12 ; or (v) said NR 15 R 16 .

3. The compound of formula (I) according to claim 1 , wherein said R 1 and said R 2 are independently of each other selected from

4. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other selected from

5. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other selected from

6. The compound of formula (I) according to claim 1 , wherein said compound is selected from

4-(difluoromethyl)-5-(2,6-dimorpholinopyrimidin-4-yl)pyridin-2-amine;

4′-(difluoromethyl)-2,6-dimorpholino-[4,5′-bipyrimidin]-2′-amine;

4-(difluoromethyl)-5-(4,6-dimorpholinopyrimidin-2-yl)pyridin-2-amine;

4′-(difluoromethyl)-4,6-dimorpholino-[2,5′-bipyrimidin]-2′-amine;

5-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrimidin-4-yl)-4-(difluoromethyl)pyridin-2-amine;

5-(2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholinopyrimidin-4-yl)-4-(difluoromethyl)pyridin-2-amine;

2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-4′-(difluoromethyl)-6-morpholino-[4,5′-bipyrimidin]-2′-amine;

5-(2,6-bis((S)-3-methylmorpholino)pyrimidin-4-yl)-4-(difluoromethyl)pyridin-2-amine;

4′-(difluoromethyl)-2,6-bis((S)-3-methylmorpholino)-[4,5′-bipyrimidin]-2′-amine;

(S)-4-(difluoromethyl)-5-(6-(3-methylmorpholino)-2-morpholinopyrimidin-4-yl)pyridin-2-amine;

(S)-4′-(difluoromethyl)-6-(3-methylmorpholino)-2-morpholino-[4,5′-bipyrimidin]-2′-amine;

(S)-4-(difluoromethyl)-5-(2-(3-methylmorpholino)-6-morpholinopyrimidin-4-yl)pyridin-2-amine;

(S)-4′-(difluoromethyl)-2-(3-methylmorpholino)-6-morpholino-[4,5′-bipyrimidin]-2′-amine;

and

(4S,5R)-3-[6-[2-amino-4-(difluoromethyl)pyrimidin-5-yl]-2-morpholino-pyrimidin-4-yl]-4-(hydroxymethyl)-5-methyl-oxazolidin-2-one.

7. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other a morpholinyl of formula (II).

8. The compound of formula (I) according to claim 7 , wherein R 1 is equal to R 2 .

9. The compound of formula (I) according to claim 7 , wherein R 1 is not equal to R 2 .

10. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other a morpholinyl of formula (II) and said 5- to 6-membered heteroaryl ring W.

11. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other a morpholinyl of formula (II) and said saturated 4- to 6-membered heterocyclic ring Z.

12. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other a morpholinyl of formula (II) and said OR 12 .

13. The compound of formula (I) according to claim 1 , wherein R 1 and R 2 are independently of each other a morpholinyl of formula (II) and said NR 15 R 16 .

14. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 and a pharmaceutically acceptable carrier.