2,4-pyrimidinediamine compounds and their uses

1. A compound according to the formula:

or a salt thereof, wherein:

R 2 is selected from phenyl mono-substituted at the 3- or 5-position with an R 8 group and phenyl di- or tri-substituted with the same or different R 8 groups;

R 4 is phenyl substituted with one or more of the same or different R 8 groups;

R 5 is halogen;

R 6 is hydrogen;

R 8 is selected from the group consisting of R a , R b , R a 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 (C1-C6) alkyl, (C3-C8)cycloalkyl, cyclohexyl, (C4-C11)cycloalkylalkyl, (C5-C10)aryl, phenyl, (C6-C16)arylalkyl, benzyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 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 , —OH, (C 1 -C 3 )haloalkyloxy, —OCF 3 , ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —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, each R c is taken together with the nitrogen atom to which it is 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 a protecting group or R a ;

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

each n is independently an integer from 0 to 3, with the provisos that:

(1) R 2 is not 3,4,5-tri (C 1 -C 6 )alkoxyphenyl; and

(2) the compound is not

N2,N4-bis(3-methylphenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis(3-chlorophenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis(2,5-dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis(3,4-dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis(2,4-dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis(3-bromophenyl)-5-fluoro-2,4-pyrimidinediamine;

N2,N4-bis[(3-chloro-4-methoxyphenyl)]-5-fluoro-2,4-pyrimidinediamine; or

N2,N4-Bis(3-chloro-4-methoxy)-5-fluoro-2,4-pyrimidinediamine.

2. The compound of claim 1 , wherein R 2 is phenyl di-substituted with the same or different R 8 groups.

3. The compound of claim 2 , wherein R 2 is 3,4-substituted.

4. The compound of claim 1 , wherein R 4 is mono-substituted with an R 8 group.

5. The compound of claim 4 , wherein R 4 is para-substituted with the R 8 group.

6. The compound of claim 1 , wherein R 5 is fluoro.

7. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

8. The composition of claim 7 , wherein the compound is in the form of a pharmaceutically acceptable salt.

9. A method for treating a subject suffering from a disease or condition mediated by the regulation or inhibition of Syk kinase, wherein the disease or condition is selected from the group consisting of scleroderma, increased fibrosis, keloids, post-surgical scars, pulmonary fibrosis, vascular spasms, migraine, reperfusion injury, post myocardial infarction, chronic obstructive pulmonary disease, cardiobronchitis, post myocardial infarction, osteoarthritis, ulcerative colitis, Crohn's disease, idiopathic inflammatory bowel disease, irritable bowel syndrome, spastic colon, inflammatory bowel disease, inflammation, and scarring, the method comprising administering to the subject an effective amount of a compound according to claim 1 .

10. A method for treating a subject suffering from an allergic disease or condition mediated by the regulation or inhibition of Syk kinase, wherein the allergic disease or condition is selected from the group consisting of conjunctivitis, rhinitis, asthma, atopic dermatitis and food allergies, the method comprising administering to the subject an effective amount of a compound according to claim 1 .

11. The compound according to claim 1 wherein the phenyl of R 2 or R 4 is trisubstituted at the 3, 4, and 5 positions.