Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds

1. A method of treating an autoimmune disease and/or one or more symptoms associated therewith, comprising the step of administering to a subject suffering from an autoimmune disease an effective amount of a 2,4-pyrimidinediamine compound according to structural formula (I):

or a salt, hydrate, solvate and/or N-oxides thereof, wherein:

the autoimmune disease is selected from the group consisting of Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, Goodpasture's disease, autoimmune thrombocytopenia, sympathetic opthalmia, myasthenia gravis, Graves' disease, primary biliary cirrhosis, chronic aggressive hepatitis, membranous glomerulopathy and an autoimmune disease involving a systemic autoimmune disorder;

L 1 and L 2 are each a direct bond;

R 2 is selected from the group consisting of phenyl mono-substituted at the 3- or 5-position with an R 8 group, phenyl di-or tri-substituted with one or more of the same or different R 8 groups, and 5-15 membered heteroaryl optionally substituted with one or more of the same or different R 8 groups;

R 4 is selected from the group consisting of phenyl substituted with one or more of the same or different R 8 groups and 5-15 membered heteroaryl optionally substituted with one or more of the same or different R 8 groups;

R 5 is selected from the group consisting of —CN, —NC, —NO 2 , fluoro, (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, (C1-C3) haloalkoxy, (C1-C3) perhaloalkoxy, —C(O)R a , —C(O)OR a , —C(O)CF 3 and —C(O)OCF 3 ;

R 6 is hydrogen;

R 8 is selected from the group consisting of selected from the group consisting of R e , R b , R e substituted with one or more of the same or different R a or R b , —OR a substituted with one or more of the same or different R a or R b , —B(OR a ) 2 , —B(NR c R c ) 2 , —(CH 2 ) m —R b , —(CHR a ) m —R b , —O—(CH 2 ) m —R b , —S—(CH 2 ) m —R b , —O—CHR a R b , —O—CR a (R b ) 2 , —O—(CHR a ) m —R b , —O—(CH 2 ) m —CH[(CH 2 ) m R b ]R b , —S—(CHR a ) m —R b , —C—(O)NH—(CH 2 ) m —R b , —C(O)NH—(CHR a ) m —R b , —O—(CH 2 ) m —C(O)NH—(CH 2) m —R b , —S—(CH 2 ) m —C(O)NH—(CH 2 ) m —R b , —O—(CHR a ) m —C(O)NH—(CHR a ) m —R b , —S—(CHR a ) m —C(O)NH—(CHR a ) m —R b , —NH—(CH 2 ) m —R b , —NH—(CHR a ) m —R b , —NH[(CH 2 ) m R b ], —N[(CH 2 ) m R b ] 2 , —NH—C(O)—NH—(CH 2 ) m R b , —NH—C(O)—(CH 2 ) m —CHR b R b and —NH—(CH 2 ) m —C(O)—NH—(CH 2 ) m —R b ;

each R a is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl,(C4-C11) cycloalkylalkyl, (C5-C10) aryl, (C6-C16) arylalkyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl;

each R b is a suitable group independently selected from the group consisting of ═O, —OR d , (C1-C3) haloalkyloxy, ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c ,—S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —C(NR a )NR c R c , —C(NOH)R a , —C(NOH)NR c R c , —OC(O)R d , —OC(O)OR d , —OC(O)NR c R c , —OC(NH)NR c R c , —OC(NR a )NR c R c , —[NHC(O)] n R d , —[NR a C(O)] n R d , —[NHC(O)] n OR d , —[NR a C(O)] n OR d , —[NHC(O)] n NR c R c , —[NR a C(O)] n NR c R c , —[NHC(NH)] n NR c R c and —[NR a C(NR a )] n NR c R c ;

each R c is independently a protecting group or R a , or, alternatively, two R c are taken together with the nitrogen atom to which they are bonded to form a 5- to 8-membered cycloheteroalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R a or suitable R b groups;

each R d is independently an R a ;

each R e is independently selected from the group consisting of (C1-C6) alkyl, (C3-C8) cycloalkyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, (C6-C16) arylalkyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, 4-11 membered cycloheteroalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl;

each m is independently an integer from 1 to 3; and

each n is independently an integer from 0 to 3;

wherein one or both of R 2 and R 4 , independently of one another, is an optionally substituted heteroaryl selected from the group consisting of:

wherein

p is an integer from one to three;

each - - - independently represents a single bond or a double bond;

R 35 is hydrogen or R 8 ;

X is selected from the group consisting of CH, N and N—O;

each Y is independently selected from the group consisting of O, S and NH;

each Y 1 is independently selected from the group consisting of O, S, SO, SO 2 ,SONR 36 , NH and NR 37 ;

each Y 2 is independently selected from the group consisting of CH, CH 2 , O, S, N, NH and NR 37 ;

R 36 is hydrogen or alkyl;

R 37 is selected from the group consisting of hydrogen, aryl, arylalkyl, heteroaryl, R a , R b —CR a R b —O—C(O)R 8 , —CR a R b —O—PO(OR 8 ) 2 , —CH 2 —O—PO(OR 8 ) 2 , —CH 2 —PO(OR) 2 , —C(O)—CR a R b —N(CH 3 ) 2 , —CR a R b —O—C(O)—CR a R b —N(CH 3 ) 2 , —C(O)R 8 , —C(O)CF 3 and —C(O)—NR 8 —C(O)R 8 ;

R 38 is selected from the group consisting of alkyl and aryl;

A is selected from the group consisting of O, NH and NR 38 ;

R 9 ,R 10 ,R 11 and R 12 are each, independently of one another, selected from the group consisting of alkyl, alkoxy, halogen, haloalkoxy, aminoalkyl and hydroxyalkyl, or, alternatively, R 9 and R 10 and/or R 11 and R 12 are taken together form an oxo group;

each Z is selected from the group consisting of hydroxyl, alkoxy, aryloxy, ester, and carbamate;

Q is selected from the group consisting of —OH, OR 8 , —NR c R c , —NR 39 —C(O)R 8 , —NR 39 —C(O)OR 8 , —NR 39 —CHR 40 —R b , and —NH—(CH 2 ) m —R b ;and

R 39 and R 40 are each, independently of one another, selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl.

2. The method of claim 1 , in which R 2 is selected from the group consisting of phenyl, benzodioxanyl, benzodioxolyl, benzoxazinyl, benzoxazolyl, benzopyranyl, benzotriazolyl, 1,4-benzoxazinyl-2-one, 2H-1,4-benzoxazinyl-3(4H)-one, 2H-1,3-benzoxazinyl-2,4(3H)-dione, benzoxazolyl-2-one, dihydrocoumarinyl, 1,2-benzopyronyl, benzofuranyl, benzo[b]furanyl, indolyl, and pyrrolyl each of which may be optionally substituted with one or more of the same or different R 8 groups.

3. The method of claim 1 in which R 2 and R 4 are the same.

4. The method of claim 3 in which each R 35 is independently selected from the group consisting of hydrogen, R d , —NR c R c , —(CH 2 ) m —NR c R c , —C(O)NR c R c , —(CH 2 ) m —C(O)NR c R c , —C(O)OR d , —(CH 2 ) m —C(O)OR d and —(CH 2 ) m —OR d .

5. The method of claim 4 in which each m is one.

6. The method of claim 1 in which R 2 is an optionally substituted 5-15 membered heteroaryl which is attached to the remainder of the molecule via a ring carbon atom.

7. The method of claim 1 in which R 4 is an optionally substituted 5-15 membered heteroaryl which is attached to the remainder of the molecule via a ring carbon atom.

8. The method of claim 1 in which one of R 2 or R 4 is a phenyl substituted with one, two or three R 8 groups.

9. The method of claim 8 in which the substituted phenyl is mono substituted.

10. The method of claim 9 in which the R 4 phenyl is substituted at the ortho, meta or para position.

11. The method of claim 10 in which R 8 is selected from the group consisting of (C1-C10) alkyl, (C1-C10) branched alkyl, —OR d , —O—(CH 2 ) m —NR c R c , —O—C(O)NR c R c , —O—(CH 2 ) m —C(O)NR c R c , —O—C(O)OR a , —O—(CH 2 ) m —C(O)OR a , —O—C(NH)NR c R c , —O—(CH 2 ) m —C(NH)NR c R c , —NH—(CH 2 ) m —NR c R c , —NH—C(O)NR c R c and —NH—(CH 2 ) m —C(O)NR c R c .

12. The method of claim 8 in which the substituted phenyl is disubstituted.

13. The method of claim 12 in which the R 8 substituents are positioned 2,3-; 2,4-; 2,5-; 2,6-; 3,4-; or 3,5-.

14. The method of claim 12 in which each R 8 is independently selected from the group consisting of(C1-C10) alkyl, (C1-C10) branched alkyl, —OR a optionally substituted with one or more of the same or different R a or R b groups, —O—(CH 2 ) m —NR c R c , —O—C(O)NR c R c , —O—(CH 2 ) m —C(O)NR c R c ,—O—C(O)OR a , —O—(CH 2 ) m —C(O)OR a , —O—C(NH)NR c R c , —O—(CH 2 ) m —C(NH)NR c R c , —NH—(CH 2 ) m —NR c R c , —NH—C(O)NR c R c and —NH—(CH 2 ) m —C(O)NR c R c .

15. The method of claim 8 in which the substituted phenyl is trisubstituted.

16. The method of claim 15 in which the R 8 substituents are positioned 2,3,4-; 2,3,5-; 2,3,6-; 2,4,5-; 2,4,6-; 2,5,6-; or 3,4,5-.

17. The method of claim 16 which each R 8 is independently selected from the group consisting of (C1-C10) alkyl, (C1-C10) branched alkyl,—OR a optionally substituted with one or more of the same or different R a or R b groups, —O—(CH 2 ) m —NR c R c , —O—C(O)NR c R c , —O—(CH 2 ) m —C(O)NR c R c , —O—C(O)OR a , —O—C(NH)NR c R c , —O—(CH 2 ) m —C(O)OR a , —O—(CH 2 ) m —C(NH)NR c R c , —NH—(CH 2 ) m —NR c R c , —NH—C(O)NR c R c and —NH—(CH 2 ) m —C(O)NR c R c .

18. The method of claim 15 in which the trisubstituted phenyl has the formula:

wherein: R 31 is methyl or (C1-C6) alkyl; R 32 is hydrogen, methyl or (C1-C6) alkyl; and R 33 is a halo group.

19. The method of claim 1 in which the 2,4-pyrimidinediamine compound is a compound according to structural formula (Ic):

or a salt, hydrate, solvate and/or N-oxide thereof, wherein:

R 4 is an optionally substituted heteroaryl; and

R 18 is —O(CH 2 ) m —R b .

20. The method of claim 19 in which R 18 is —O—CH 2 —C(O)—NHCH 3 .

21. The method of claim 1 in which the 2,4-pyrimidinediamine compound is selected from the group consisting of compounds

N4-[(2,2-Dimethyl-4H-benzo[1,4]oxazin-3 -one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine (R940323),

N4-[(2 ,2-Dimethyl-4H-5-pyrido [1 ,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine (R940347) and

N4-[(2,2-Difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine (R921303).

22. The method of claim 1 in which the 2,4-pyrimidinediamine compound is administered in the form of a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier, diluent or excipient.

23. The method of claim 1 in which the autoimmune disease is an autoimmune disease involving systemic autoimmune disorder.

24. The method of claim 23 in which the autoimmune disease involving systemic autoimmune disorder is selected from the group consisting of systemic lupus erythematosis, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis and bullous pemphigoid.

25. The method of claim 24 in which the autoimmune disease is systemic lupus erythematosis.

26. The method of claim 24 in which the autoimmune disease is rheumatoid arthritis.

27. The method of claim 24 in which the autoimmune disease is multiple sclerosis.

28. The method of claim 1 , wherein the 2,4-pyrimidinediamine compound is selected from the group consisting of:

7.4.35

N4-(2-Aminopyrid-6-yl)-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.36

N4-[2-(N-Acetylamino)pyrid-6-yl]-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.39

N2-(3,5-Dichloro-4-hydroxyphenyl)-N4-(2,2-difluoro-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.40

N2-(3,5-Dichloro-4-hydroxyphenyl)-N4-(2,2-dimethyl-3-oxo-

4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.44

N2-(3,5-Dichloro-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-

4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.45

N2-(3,5-Dichloro-4-methoxyphenyl)-N4-(2,2-difluoro-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.46

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-3-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.50

N4-[2-Aminopyrid-6-yl)-N2-(3,5-dimethoxyphenyl)-5-fluoro-2,

4-pyrimidinediamine

7.4.51

N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(indol-6-yl)-2,4-

pyrimidinediamine

7.4.52

N4-[2-(N-Acetylamino)pyrid-6-yl]-N2-(3,5-dimethoxyphenyl)-5-

fluoro-2,4-pyrimidinediamine

7.4.53

N2-(3,5-Dichlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.54

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

(3-methoxy-5-trifluoromethylphenyl)-2,4-pyrimidinediamine

7.4.55

N2-(2,6-Dimethoxypyrid-3-yl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.61

N4-[2-(N-Acetylamino)pyrid-6-yl]-N2-(3,5-dimethylphenyl)-5-

fluoro-2,4-pyrimidinediamine

7.4.62

N2-(3,5-Dimethylphenyl)-5-fluoro-N4-[2-(N-

methylamino)carbonylaminopyrid-6-yl]-2,4-pyrimidinediamine

7.4.64

N4-(2-Aminopyrid-6-yl)-N2-(3-chloro-4-

trifluoromethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.65

N2-(3-Chloro-4-trifluoromethoxyphenyl)-N4-(3,4-

ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.66

N4-(2-Aminopyrid-6-yl)-N2-(3-chloro-4-methoxyphenyl)-5-

fluoro-2,4-pyrimidinediamine

7.4.67

N2-(3-Chloro-4-methoxyphenyl)-N4-(3,4-ethylenedioxyphenyl)-

5-fluoro-2,4-pyrimidinediamine

7.4.68

N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(indol-6-yl)-2,4-

pyrimidinediamine

7.4.70

N4-(2-Aminopyrid-6-yl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-

pyrimidinediamine

7.4.72

N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.73

N4-(3,4-Dichlorophenyl)-N2-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.74

N2-(4-Chloro-3,5-dimethylphenyl)-N4-(3,4-

ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.75

N2-(4-Chloro-3,5-dimethylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.76

(+)-N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[2-(N-

methylaminocarbonyl)-2,3-dihydrobenzofuran-5-yl]-5-fluoro-

2,4-pyrimidinediamine

7.4.77

(+)-N4-(3-Chloro-4-methoxyphenyl)-N2-[2-(N,N-

dimethylaminocarbonyl)-2,3-dihydrobenzofuran-5-yl]-5-fluoro-

2,4-pyrimidinediamine

7.4.78

(+)-N4-(3-Chloro-4-trifluoromethoxyphenyl)-N2-[2-(N,N-

dimethylaminocarbonyl)-2,3-dihydrobenzofuran-5-yl]-5-fluoro-

2,4-pyrimidinediamine

7.4.79

(+)-N4-(3-Chloro-4-methoxyphenyl)-N2-[2-(N-

methylaminomethylene)-2,3-dihydrobenzofuran-5-yl]-5-fluoro-

2,4-pyrimidinediamine

7.4.80

5-Fluoro-N2-[2(R)-{(1R, 2S, 5R)-menthyloxycarbonyl}-2,3-

dihydrobenzofuran-5-yl]-N4-(4-isopropoxyphenyl)-2,4-

pyrimidinediamine

7.4.81

N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[2(R)-{

(1R, 2S, 5R)-menthyloxycarbonyl}-2,3-dihydrobenzofuran-5-

yl]-5-fluoro-2,4-pyrimidinediamine

7.4.82

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine p-

Toluenesulfonic Acid Salt

7.4.83

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine —

Methanesulfonic Acid Salt

7.4.84

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine —

Benzenesulfonic Acid Salt

7.4.85

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine Hydrogen

Chloride Salt

7.4.86

N2-(3,5-Dimethoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine DL-

Camphoursulfonic Acid Salt

7.4.87

N2-(3,5-Dimethylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

p-Tolunesulfonic Acid Salt

7.4.88

N2-(3,5-Dimethylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

Benzenesulfonic Acid Salt

7.4.89

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(indol-6-yl)-2,4-

pyrimidinediamine p-Toluenesulfonic Acid Salt

7.4.90

N4-(3,4-Ethylendioxyphenyl)-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine p-Toluenesulfonic Acid Salt

7.4.101

(+) N2-(2-Carboxyl-2,3-dihydrobenzofuran-5-yl)-N4-(3-chloro-

4-trifluoromethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.102

(+) N4-(3-Chloro-4-trifluoromethoxyphenyl)-5-fluoro-N2-[2-

(N-2,3-dihydroxypropylamino)carbonyl-2,3-dihydrobenzofuran-

5-yl]-2,4-pyrimidinediamine

7.4.103

(+) N4-(3-Chloro-4-trifluoromethoxyphenyl)-5-fluoro-N2-[2-

(N-2-hydroxyethylamino)carbonyl-2,3-dihydrobenzofuran-5-yl]-

2,4-pyrimidinediamine

7.4.104

(+) N4-(3-Chloro-4-trifluoromethoxyphenyl)-5-fluoro-N2-[2-(N-

2-hydroxyethyl-N-methylamino]carbonyl-2,3-dihydrobenzo-

furan-5-yl]-2,4-pyrimidinediamine

7.4.105

N4-(3-Chloro-4-trifluoromethoxyphenyl)-5-fluoro-N2-[2-(N-

isopropylamino)carbonyl-2,3-dihydrobenzofuran-5-yl]-2,4-

pyrimidinediamine

7.4.106

5-Fluoro-N4-(2-isopropoxypyridin-5-yl)-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.114

N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-(3,5-

dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.115

N2-(3-Chloro-4-hydroxy-5-methylphenyl)-N4-(2,2-difluoro-3-

oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.119

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(indol-6-yl)-2,4-

pyrimidinediamine

7.4.120

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(indol-6-yl)-2,4-

pyrimidinediamine

7.4.121

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

(indol-6-yl)-2,4-pyrimidinediamine

7.4.122

N4-(3-Chloro-4-methoxyphenyl)-N2-[2-(N,N-

dimethylaminomethyl)benzofuran-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.123

N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[2-(N,N-

dimethylaminomethyl)benzofuran-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.124

N4-(3,4-Dichlorophenyl)-N2-[2-(N,N-

dimethylaminomethyl)benzofuran-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.125

N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-difluoro-3-oxo-4H-

benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.126

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

(indol-6-yl)-2,4-pyrimidinediamine

7.4.127

N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[2-(N,N-

dimethylaminocarbonyl)-2,3-dihydrobenzofuran-5-yl]-5-fluoro-

2,4-pyrimidinediamine

7.4.128

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

(3-methoxy-5-trifluoromethylphenyl)-2,4-pyrimidinediamine

7.4.129

N2-(3,5-Dichlorophenyl)-N4-(2,2-difluoro-3-oxo-4H-benz[1,4]

oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.137

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

(3,4,5-trimethylphenyl)-2,4-pyrimidinediamine

7.4.147

N2-(3-Chloro-4-hydroxy-5-methylphenyl)-N4-(2,2-dimethyl-3-

oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.148

N2-(3-Chloro-4-methoxy-5-methylphenyl)-N4-(2,2-dimethyl-3-

oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.149

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

(indazolin-6-yl)-2,4-pyrimidinediamine

7.4.150

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

(indazolin-6-yl)-2,4-pyrimidinediamine

7.4.153

5-Fluoro-N4-[2-methyl-2-(N-methylaminocarbonyl)-3-oxo-4H-

benz[1,4]oxazin-6-yl]-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.154

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

(N1-methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.155

N4-(2,2-Difluoro-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-(2,2-

dimethyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-2,4-

pyrimidinediamine

7.4.156

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

(1-methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.157

N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3-

chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.158

N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3,5-

dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.159

N2-(3,4-Dichlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.160

N4-[(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-

N2-(indazolin-6-yl)-2,4-pyrimidinediamine

7.4.161

N2-(3-tert-Butylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.162

N4-[(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-

N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine

7.4.163

N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3-

fluoro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.164

N2-(3-Chlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]

oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.165

N2-(3,5-Dichlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.166

N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-

N2-(1-methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.167

N2-(3-Chloro-4-trifluoromethoxyphenyl)-N4-(2,2-dimethyl-3-

oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.168

N2-(3-Chloro-4-methoxy-5-methylphenyl)-N4-(2,2-dimethyl-3-

oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.169

N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-

N2-(3-methoxycarbonylmethyleneoxyphenyl)-2,4-

pyrimidinediamine

7.4.170

N2-(3-Chloro-4-hydroxy-5-methylphenyl)-N4-(3,4-

ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.171

N2-(3-Chloro-4-hydroxy-5-methylphenyl)-N4-(2,2-dimethyl-3-

oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.172

N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-

4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.173

N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(3,4-

ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.174

N2-(3-Chloro-4-methoxy-5-methylphenyl)-N4-(3,4-

ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.183

(+) N4-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl)-5-

fluoro-N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl]-

2,4-pyrimidinediamine

7.4.186

(+) 5-Fluoro-N4-[4-(N-methyl)amino-1-benzopyran-6-yl[-N2-[3-

(N-methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.187

(+) N4-[4-(N-tert-Butoxycarbonyl-N-methyl)amino-1-

benzopyran-6-yl]-5-fluoro-N2-[3-(N-methylamino)carbonyl-

methyleneoxyphenyl]-2,4-pyrimidinediamine

7.4.194

(S)-N4-[4-(N-Benzyloxycarbonyl)amino-1-benzopyran-6-yl]-5-

fluoro-N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl]-

2,4-pyrimidinediamine

7.4.195

(R)-N4-[4-(N-Benzyloxycarbonyl)amino-1-benzopyran-6-yl]-5-

fluoro-N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl]-

2,4-pyrimidinediamine

7.4.196

(S)-N4-(4-Amino-1-benzopyran-6-yl)-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.197

(R)-N4-(4-Amino-1-benzopyran-6-yl)-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.198

(+) N4-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-5-

fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine

7.4.199

(+) N4-(4-Amino-1-benzopyran-6-yl)-5-fluoro-N2-(indazol-6-

yl)-2,4-pyrimidinediamine

7.4.200

(+) N4-(4-Amino-1-benzopyran-6-yl)-N2-(3,5-dichloro-4-

methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.201

(+) N4-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-

N2-(3,5-dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.202

(+) N4-(4-Amino-1-benzopyran-6-yl)-N2-(3,5-

dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.203

(+) N4-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-

N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.204

(+) N4-(4-Amino-1-benzopyran-6-yl)-N2-(3-chloro-4-

methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.205

(+) N4-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-

N2-(3,4-dichlorophenyl)-5-fluoro 2,4-pyrimidinediamine

7.4.206

(+) N4-(4-Amino-1-benzopyran-6-yl)-N2-(3,4-dichlorophenyl)-

5-fluoro-2,4-pyrimidinediamine

7.4.207

(+) N2-[4-(N-tert-Butoxycarbonylamino-1-benzopyran-6-yl]-N4-

(3,5-dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.208

(+) N2-[4-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-

N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.209

N2-[4(R,S)-(N-tert-Butoxycarbonyl)amino-1-benzopyran-6-yl]-

5-fluoro-N4-[2-(S)-methyl-3-oxo-4H-benz[1,4]oxazin-6-yl]-2,4-

pyrimidinediamine

7.4.210

(+) N2-(4-Amino-1-benzopyran-6-yl]-N4-(3,5-

dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.211

(+) N2-(4-Amino-1-benzopyran-6-yl)-N4-(3,4-dichlorophenyl)-

5-fluoro 2,4-pyrimidinediamine

7.4.213

N2-[4(R,S)-Amino-1-benzopyran-6-yl)-5-fluoro-N4-(2(S)-

methyl-3-oxo-4H-benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine

7.4.245

(+)-5-Fluoro-N2-[3-(N-methylamino)carbonyl-

methyleneoxyphenyl]-N4-[4-(N-p-toluenesulfonyl)amino-1-

benzopyran-6-yl)-2,4-pyrimidinediamine

7.4.247

(+)-5-Fluoro N4-[4-(N-methanesulfonyl)amino-1-benzopyran-6-

yl)-N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.248

(+)-N4-[4-N-(N,N-Dimethylaminomethylencarbonyl)amino-1-

benzopyran-6-yl]-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.249

(+)-N4-[4-N-(N,N-Dimethylaminomethylencarbonyl)-N-

methylamino-1-benzopyran-6-yl]-5-fluoro-N2-[3-(N-

methylamino)carbonylmethyleneoxyphenyl]-2,4-

pyrimidinediamine

7.4.281

N2-[3-(N-Cyclobutylamino)carbonylmethyleneoxyphenyl]-5-

fluoro-N4-(2H-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-2,4-

pyrimidinediamine

7.4.282

N2-[3-(N-Cyclopropylamino)carbonylmethyleneoxyphenyl]-5-

fluoro-N4-(2H-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-2,4-

pyrimidinediamine

7.4.290

N2-(3,4-Dichlorophenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.291

N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.292

N2-(3,5-Dichloro-4-methoxyphenyl)-5-fluoro-N4-(2H-3-oxo-4H-

5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.293

N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.294

5-Fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.297

N2-(3,4-Ethylenedioxyphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.306

N4-(2,2-Difluoro-2H-3-oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-

N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl)-2,4-

pyrimidinediamine p-Toluenesulfonic Acid Salt

7.4.307

N4-(2,2-Difluoro-2H-3-oxo-4H-benz[1,4]oxazin-6-yl)-5-fluoro-

N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl)-2,4-

pyrimidinediamine Benzenesulfonic Acid Salt

7.4.314

N2-(3,4-Dimethoxyphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.316

N2-[3-(N-Cyclobutylamino)carbonylmethyleneoxyphenyl]-N4-

(2,2-dimethyl-2H-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-

2,4-pyrimidinediamine

7.4.319

N2-(3,5-Dimethylphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.320

N2-(3,5-Dimethylphenyl)-N4-(2,2-dimethyl-2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.321

5-Fluoro-N2-(3-isopropylphenyl)-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.322

N2-(3-Chloro-4-methylphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.323

5-Fluoro-N2-(3-methoxy-5-trifluoromethylphenyl)-N4-(2H-3-

oxo-4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.324

5-Fluoro-N2-(indol-6-yl)-N4-(2H-3-oxo-4H-5-pyrid[1,4]oxazin-

6-yl)-2,4-pyrimidinediamine

7.4.325

N4-(2,2-dimethyl-2H-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-

fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine

7.4.326

N2-(3,5-Dichlorophenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.327

N2-(3-Bromophenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-pyrid[1,4]

oxazin-6-yl)-2,4-pyrimidinediamine

7.4.328

N2-(3-tert-Butylphenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.329

N2-(3,4-Difluorophenyl)-5-fluoro-N4-(2H-3-oxo-4H-5-

pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.342

(S)-5-Fluoro-N2-[3-(N-methylamino)carbonyl-

methyleneoxyphenyl]-N4-(2-methyl-3-oxo-4H-benz[1,4]oxazin-

6-yl)-2,4-pyrimidinediamine

7.4.343

N4-(4,4-Dimethyl-1,3-dioxo-2H,4H-isoquinolin-7-yl)-5-fluoro-

N2-[3-(N-methylamino)carbonylmethylenedioxyphenyl]-2,4-

pyrimidinediamine

7.4.344

(R)-5-Fluoro-N2-[3-(N-methylamino)carbonyl-

methyleneoxyphenyl]-N4-(2-methyl-3-oxo-4H-benz[1,4]oxazin-

6-yl)-2,4-pyrimidinediamine

7.4.345

N2-(3-Chloro-4-hydrox-5-methylyphenyl)-N4-(4,4-dimethyl-

1,3-dioxo-2H,4H-isoquinolin-7-yl)-5-fluoro-2,4-

pyrimidinediamine

7.4.346

(S)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-

oxo-4H-benz[1,4]oxazin[6-yl)-2,4-pyrimidinediamine

7.4.347

(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-

oxo-4H-benz[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.348

N2-(3,5-Dimethoxyphenyl)-N4-(4,4-dimethyl-1,3-dioxo-2H,4H-

isoquinolin-7-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.349

(S)-N2-(3,5-Dichloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-

3-oxo-4H-benz[1,4]-oxazin-6-yl)-2,4-pyrimidinediamine

7.4.350

(R)-N2-(3,5-Dichloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-

3-oxo-4H-benz[1,4]-oxazin-6-yl)-2,4-pyrimidinediamine

7.4.351

(+)-N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-[2-(2-hydroxy-

ethyl)-3-oxo-4H-benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine

7.4.352

(+)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-[2-(2-hydroxy-

ethyl)-3-oxo-4H-benz[1,4]oxazin-6-yl]-2,4-pyrimidinediamine

7.4.353

(S,S)-N2,N4-Bis-(2-methyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-5-

fluoro-2,4-pyrimidinediamine

7.4.354

(S)-N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-

4H-benz[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.355

(R)-N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-

4H-benz[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

7.4.356

N2-(3,5-Dichloro-4-methoxyphenyl)-N4-(4,4-dimethyl-1,3-

dioxo-2H,4H-isoquinolin-7-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.357

N4-(4,4-Dimethyl-1,3-dioxo-2H,4H-isoquinolin-7-yl)-N2-

(indazol-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.358

N4-(3,3-Dimethyl-4H-benz[1,4]oxazin-6-yl)-N2-(3,5-

dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine

7.4.359

N2-(3-Chloro-4-methoxyphenyl)-N4-(3,3-dimethyl-4H-

benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

7.4.360

N4-(3,3-Dimethyl-1,4-benzoxazin-6-yl)-5-fluoro-N2-(indazol-6-

yl)-2,4-pyrimidinediamine

7.4.361

N4-(3,3-Dimethyl-4H-benz[1,4]oxazin-6-yl)-5-fluoro-N2-(N1-

methylindazol-6-yl)-2,4-pyrimidinediamine

7.4.362

(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-

oxo-4H-benz[1,4]oxazin-6-yl)-2,4-pyrimidinediamine

Toluenesulfonic Acid Salt

7.4.372

N4-(2,6-Dimethoxypyrid-3-yl)-N2-[1-(2-

ethoxycarbonylethyl)indazolin-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.373

N4-(4-Chlorophenyl)-5-fluoro-N2-{1-[2-(N-

methylamino)carbonylethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.374

N4-(4-Chlorophenyl)-5-fluoro-N2-[1-(3 -hydroxy-

propyl)indazolin-5-yl]-2,4-pyrimidinediamine

7.4.375

N4-(3,4-Difluorophenyl)-N2-[1-(2-ethoxycarbonyl-

ethyl)indazolin-5-yl]-5-fluoro-2,4-pyrimidinediamine

7.4.376

N4-(3,4-Difluorophenyl)-5-fluoro-N2-{1-[2-(N-

methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.377

N4-(3,4-Difluorophenyl)-5-fluoro-N2-[1-(3-hydroxy-

propyl)indazolin-5-yl]-2,4-pyrimidinediamine

7.4.378

N4-(3,4-Dichlorophenyl)-N2-[1-(2-ethoxycarbonyl-

ethyl)indazolin-5-yl]-5-fluoro-2,4-pyrimidinediamine

7.4.379

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-{1-[2(N-

methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.380

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-hydroxy-

propyl)indazolin-5-yl]-2,4-pyrimidinediamine

7.4.381

N4-(3,4-Ethylenedioxyphenyl)-5-fluoro-N2-(1-methylindazolin-

6-yl)-2,4-pyrimidinediamine

7.4.382

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(1-methylindazolin-

6-yl)-2,4-pyrimidinediamine

7.4.384

N2-(3-Chloro-4-hydroxy-5-methylphenyl)-5-fluoro-N4-(1-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.385

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[2-(2-methoxy-4-

methoxycarbonylbenzyl)indazolin-6-yl]-2,4-pyrimidinediamine

7.4.386

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[2-(2-methoxy-4-

methoxycarbonylbenzyl)indazolin-6-yl]-2,4-pyrimidinediamine

7.4.387

N4-(3,4-Ethylenedioxyphenyl)-5-fluoro-N2-{1-[2-methoxy-4-

(N-methylaminocarbonyl)benzyl]indazolin-6-yl}-2,4-

pyrimidinediamine

7.4.388

N4-(3, 4-Difluorophenyl)-5-fluoro-N2-(indazolin-6-yl)-2,4-

pyrimidinediamine

7.4.389

N4-(3,4-Difluorophenyl)-5-fluoro-N2-(1-methylindazolin-6-yl)-

2,4-pyrimidinediamine

7.4.390

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(1-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.391

N4-(3,4-Dichlorophenyl)-N2-[1-(2-ethoxy-

carbonylethyl)indazolin-6-yl]-5-fluoro-2,4-pyrimidinediamine

7.4.392

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-{1-[2(N-

methylamino)carbonylethyl]indazolin-6-yl}-2,4-

pyrimidinediamine

7.4.393

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-{1-(3-

hydroxypropyl)indazolin-6-yl]-2,4-pyrimidinediamine

7.4.394

N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(2-

ethoxycarbonylethyl)indazolin-6-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.395

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-

hydroxypropyl)indazolin-6-yl]-2,4-pyrimidinediamine

7.4.396

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(indazolin-6-yl)-

2,4-pyrimidinediamine

7.4.397

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-{1-[2-(N-

methylaminocarbonyl)ethyl]indazolin-6-yl}-2,4-

pyrimidinediamine

7.4.398

5-Fluoro-N4-(4-fluoro-3-methoxyphenyl)-5-fluoro-N2-(1-

methylindazolin-5-yl)-2,4-pyrimidinediamine

7.4.399

N4-(4-Chloro-3-fluorophenyl)-5-fluoro-N2-(1-methylindazolin-

5-yl)-2,4-pyrimidinediamine

7.4.400

N4-(3,4-Dimethoxyphenyl)-5-fluoro-N2-1 -methylindazolin-5-

yl)-2,4-pyrimidinediamine

7.4.401

N2-(3-Chloro-4-methoxy-5-methylphenyl)-5-fluoro-N4-

(indazolin-6-yl)-2,4-pyrimidinediamine

7.4.402

N4-(4-Chloro-3-fluorophenyl)-5-fluoro-N2-(indazolin-6-yl)-2,4-

pyrimidinediamine

7.4.403

N4-(4-Chloro-3-fluorophenyl)-5-fluoro-N2-(indazolin-5-yl)-2,4-

pyrimidinediamine

7.4.404

5-Fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(indazolin-6-yl)-

2,4-pyrimidinediamine

7.4.405

5-Fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(indazolin-5-yl)-

2,4-pyrimidinediamine

7.4.406

N2-(3-Chloro-4-methoxy-5-methylphenyl)-5-fluoro-N4-{4H-

imidazo[2,1-c]-benz[1,4]oxazin-8-yl}-2,4-pyrimidinediamine

7.4.407

N2-(3 -Chloro-4-methoxy-5-methylphenyl)-5-fluoro-N4-(1-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.408

N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(1-methylindazolin-

6-yl)-2,4-pyrimidinediamine

7.4.410

N2-(3,5-Dimethoxyphenyl)-5-fluoro-N4-(indazolin-6-yl)-2,4-

pyrimidinediamine

7.4.411

N2-(2,2-Dimethyl-3-oxo-4H-benz[1,4]oxazine-6-yl)-5-fluoro-

N4-(1-methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.412

N4-(3-Chloro-4-fluorophenyl)-5-fluoro-N2-(1-methylindazolin-

6-yl)-2,4-pyrimidinediamine

7.4.413

N4-(3-Chloro-4-fluorophenyl)-5-fluoro-N2-(1-methylindazolin-

5-yl)-2,4-pyrimidinediamine

7.4.414

N4-(3-Chloro-4-fluorophenyl)-5-fluoro-N2-(indazolin-6-yl)-2,4-

pyrimidinediamine

7.4.415

N4-(3-Chloro-4-fluorophenyl)-5-fluoro-N2-(indazolin-5-yl)-2,4-

pyrimidinediamine

7.4.416

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

(indazolin-6-yl)-2,4-pyrimidinediamine Benzenesulfonic Acid

Salt

7.4.417

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

(indazolin-6-yl)-2,4-pyrimidinediamine p-Toluenesulfonic Acid

Salt

7.4.418

N4-(2,2-Dimethyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[1-(2-

ethoxycarbonylethyl)indazolin-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.419

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

[1-(3-hydroxypropyl)indazolin-5-yl]-2,4-pyrimidinediamine

7.4.420

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

{1-[2(N-methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.421

N4-(2,2-Dimethyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[1-(2-

ethoxycarbonylethyl)indazolin-6-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.422

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

{1-[2-(N-methylaminocarbonyl)ethyl]indazolin-6-yl}-2,4-

pyrimidinediamine

7.4.423

N4-(2,2-Dimethyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[1-

(methoxycarbonyl)methyl-indazolin-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.424

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

[1-(N-methylaminocarbonyl)methylindazolin-5-yl}-2,4-

pyrimidinediamine

7.4.425

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

(indazolin-5-yl)-2,4-pyrimidinediamine

7.4.426

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

(1-methylindazolin-5-yl)-2,4-pyrimidinediamine

7.4.427

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

(indazolin-6-yl)-2,4-pyrimidinediamine

7.4.428

N4-(3,4-Dimethoxyphenyl)-5-fluoro-N2-(indazolin-5-yl)-2,4

pyrimidinediamine

7.4.429

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

[1-(2-methoxy-4-methoxycarbonylbenzyl)indazolin-6-yl]2,4-

pyrimidinediamine

7.4.430

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(1-methylindazolin-6-yl)-

2,4-pyrimidinediamine p-Toluenesulfonic Acid Salt

7.4.431

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methylindazolin-6-yl)-

2,4 pyrimidinediamine

7.4.432

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

(2-methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.433

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(2-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.434

N4-(3,4-Dichlorophenyl)-N2-[2-(2-ethoxy-

carbonylethyl)indazolin-5yl]-5-fluoro-2,4-pyrimidinediamine

7.4.435

N4-(2,2-Dimethyl-3-oxo-4H-benz[1,4]oxazin-6-yl)-N2-[2-(2-

ethoxycarbonylethyl)indazolin-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.436

5-Fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(1-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.437

5-Fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(2-

methylindazolin-6-yl)-2,4-pyrimidinediamine

7.4.438

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-

hydroxypropyl)indazolin-5-yl]-2,4-pyrimidinediamine Bis(p-

Toluenesulfonic Acid Salt

7.4.439

N4-(3,4-Dichlorophenyl)-5-fluoro-N2-{2-[2-(N-

methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.440

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

{2-[2(N-methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine

7.4.441

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(1-

methylindazolin-5-yl)-2,4-pyrimidinediamine

7.4.442

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(indazolin-5-yl)-

2,4-pyrimidinediamine

7.4.443

N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(2-

ethoxycarbonylethyl)indazolin-5-yl]-5-fluoro-2,4-

pyrimidinediamine

7.4.444

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-

hydroxypropyl)indazolin-5-yl]-2,4-pyrimidinediamine

7.4.445

N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-{1-[2-(N-

methylaminocarbonyl)ethyl]indazolin-5-yl}-2,4-

pyrimidinediamine or a salt, hydrate, solvate or N-oxide thereof.