2,4-pyrimidinediamine compounds for treating or preventing autoimmune diseases

1. A compound according to formula I:

or a stereoisomer, salt, or N-oxide thereof, wherein:

Y is selected from the group consisting of S, O, SO, SO 2 , and C(R 7 ) 2 ;

each R 35 is independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, and halo, or both R 35 together with the carbon to which they are attached form a carbonyl group;

W is selected from the group consisting of C═O, C═S, C═NH, C(R 7 ) 2 , and NR 37 ;

Z is C═O or NR 37 , provided that Z and W are not both NR 37 and provided that when Z is C═O, then W is C(R 7 ) 2 or NR 37 ;

X is CH or N;

each R 31 is independently (C 1 -C 4 )alkyl or both R 31 together form a (C 1 -C 2 )alkyleno group optionally substituted with one to two (C 1 -C 4 )alkyl groups or substituted with one (C 3 -C 7 ) spirocycloalkyl group;

each R 7 is independently hydrogen or (C 1 -C 4 )alkyl; and

R 37 is hydrogen or methyl optionally substituted with phenyl or pyridyl, wherein said phenyl or pyridyl is optionally substituted with (C 1 -C 4 )alkoxy.

2. A compound according to claim 1 wherein Y is O or S.

3. A compound according to claim 2 wherein Y is O.

4. A compound according to claim 1 wherein both R 35 are the same.

5. A compound according to claim 4 wherein both R 35 are methyl.

6. A compound according to claim 1 wherein W is C═O or C═S.

7. A compound according to claim 6 wherein W is C═O.

8. A compound according to claim 1 wherein Z is NR 37 .

9. A compound according to claim 8 wherein Z is NH.

10. A compound according to claim 1 wherein X is N.

11. A compound according to claim 1 wherein R 31 is methyl.

12. A compound according to claim 1 wherein Z is NR 37 and R 37 is methyl, 2-pyridylmethyl, or 4-methoxybenzyl.

13. The compound of according to claim 1 selected from the group consisting of

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-[3-oxo-benzo[1,4]thiazin-6-yl]-2,4-pyrimidinediamine;

N4-[2,2-Dimethyl-3-oxo-benzo[1,4]thiazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine;

N4-[2,2-Dimethyl-3-oxo-benz[1,4]oxazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine;

N4-[2,2-Dimethyl-3-oxo-pyrid[1,4]oxazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine;

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-[3-oxo-benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine;

N4-[2,2-Difluoro-3-oxo-benz[1,4]oxazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine;

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-[3-oxo-4-(2-pyridylmethyl) -benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine;

N4-(3,4-Dihydro-2H-2,2-dimethyl-5-pyrido[1,4]oxazin-6-yl)-N2-[3,4-dimethoxyphenyl-5-hydroxyphenyl]-5-fluoro-2,4-pyrimidinediamine;

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-(1,3-(2H)-4,4-dimethylisoquinolinedione-7-yl)-2,4-pyrimidinediamine;

(R/S)-5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-[2-methyl-3-oxo-4-(4-methoxybenzyl)-benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine;

(R/S)-5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-[2-methyl-3-oxo-4-(4-methoxybenzyl)-benzo[1,4]thiazin-6-yl]-2,4-pyrimidinediamine;

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-(2,2,4-trimethyl-1,1,3-trioxo benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine; and

5-Fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-N4-(4-methyl-3-oxo-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine; or

a stereoisomer, salt, or N-oxide thereof.

14. A pharmaceutical composition comprising a compound, stereoisomer, salt, or N-oxide thereof according to claim 1 and a carrier, excipient, or diluent.

15. N4-[2,2-Dimethyl-3-oxo-benzo[1,4]thiazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine or a stereoisomer, salt, or N-oxide thereof.

16. N4-[2,2-Dimethyl-3-oxo-benz[1,4]oxazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine or a stereoisomer, salt, or N-oxide thereof.

17. N4-[2,2-Dimethyl-3-oxo-pyrid[1,4]oxazin-6-yl]-5-fluoro-N2-(3-hydroxy-4,5-dimethoxyphenyl)-2,4-pyrimidinediamine or a stereoisomer, salt, or N-oxide thereof.