2,4-pyrimidinediamine compounds and their uses
View Patent ↗The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.
1. A compound according to Formula (I):
or a salt thereof, wherein:
R 2 and R 4 are different, and wherein one of R 2 and R 4 is a phenyl monosubstituted with (C1-C10) alkyl, (C1-C10) branched alkyl, —OR a optionally substituted with one or more of the same or different R b groups, —O—C(O)OR a , —O—(CH 2 ) m —C(O)OR a , —C(O)OR a , —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(NH)NR c R c , —O—(CH 2 ) m —C(NH)NR c R c or —NH—(CH 2 ) m —NR c R c ;
the other of R 2 and R 4 is a phenyl disubstituted with R 8 ;
R 5 is fluoro, —CN, —NO 2 or (C1-C6) alkyl optionally substituted with one or more of the same or different R 8 groups;
each R 8 is independently R a or R b ;
each R a is H or (C1-C6) alkyl;
each R b is —OCF 3 , —NR c R c , —CF 3 , —CN, —NO 2 , —N 3 , —SO 2 NR c R c , —C(O)R a , —C(O)OR a , —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 ;
each R c is independently R a ; and
each m is independently an integer from 1 to 3.
2. The compound of claim 1 , wherein R 5 is halogen, (C1-C4) alkanyl optionally substituted with one or more of the same or different R 8 groups, (C2-C4) alkenyl optionally substituted with one or more of the same or different R 8 groups or (C2-C4) alkynyl optionally substituted with one or more of the same or different R 8 groups.
3. The compound of claim 2 , wherein R 5 is fluoro or (C1-C4) alkanyl optionally substituted with one or more of the same or different R 8 groups.
4. The compound of claim 3 , wherein each R b is independently —OCF 3 , —NR c R c , —CF 3 , —CN, —NO 2 , —N 3 , —SO 2 NR c R c , —C(O)R a , —C(O)OR a or —C(O)NR c R c .
5. The compound of claim 4 , wherein R 5 is fluoro or —CF 3 .
6. The compound of claim 5 , wherein each m is 1.
7. The compound of claim 6 , wherein R 5 is fluoro.
8. The compound of claim 1 , wherein R 4 is a phenyl monosubstituted with (C1-C10) alkyl, (C1-C10) branched alkyl, —OR a optionally substituted with one or more of the same or different R b groups, —O—C(O)OR a , —O—(CH 2 ) m —C(O)OR a , —C(O)OR a , —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(NH)NR c R c , —O—(CH 2 ) m —C(NH)NR c R c or —NH—(CH 2 ) m —NR c R c ; and R 2 is a phenyl disubstituted with R 8 .
9. The compound of claim 1 , wherein one of R 2 and R 4 is a phenyl monosubstituted with (C1-C10) alkyl, (C1-C10) branched alkyl, —OR a optionally substituted with one or more of the same or different R b groups, —O—C(O)OR a , —O—(CH 2 ) m —C(O)OR a , —C(O)OR a , —O—C(O)NR c R c , —O—(CH 2 ) m —C(O)NR c R c , —O—C(NH)NR c R c or —O—(CH 2 ) m —C(NH)NR c R c ; and the other of R 2 and R 4 is a phenyl disubstituted with R 8 .
10. The compound of claim 1 , wherein R 8 is not hydrogen.
11. The compound of claim 1 , wherein R 2 is phenyl disubstituted with R 8 wherein neither R 8 is hydrogen.
12. The compound of claim 1 , wherein R 4 is phenyl monosubstituted with —OR a .