Claims for Patent: 8,835,430

Summary for Patent: 8,835,430

Title:	2,4-pyrimidinediamine compounds and their uses
Abstract:	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.
Inventor(s):	Rajinder Singh, Ankush Argade, Donald Payan, Susan Molineaux, Sacha Holland, Jeffrey Clough, Holger Keim, Somasekhar Bhamidipati, Catherine Sylvain, Hui Li, Alexander Rossi
Assignee:	Rigel Pharmaceuticals Inc
Application Number:	US14/038,521
Patent Claims:	1. A compound according to the formula: or a salt thereof, wherein: R2 is phenyl tri-substituted with the same or different R8 groups; R4 is phenyl substituted with one or more of the same or different R8 groups; R2 and R4 are different; R5 is halogen; R6 is hydrogen; R8 is selected from the group consisting of Ra, Rb, —O—(CH2)m—Rb, —S—(CH2)m—Rb, —O—CHRaRb, —O—CRa(Rb)2, —O—(CHRa)m—Rb, —C(O)NH—(CH2)m—Rb, —C(O)NH—(CHRa)m—Rb, —O—(CH2)m—C(O)NH—(CH2)m—Rb, —S—(CH2)m—C(O)NH—(CH2)m—Rb, —O—(CHRa)m—C(O)NH—(CHRa)m—Rb, —NH—(CH2)m—Rb, —NH—(CHRa)m—Rb, —NH[(CH2)mRb], —N[(CH2)mRb]2, —NH—C(O)—NH—(CH2)m—Rb, —NH—C(O)—(CH2)m—CHRbRb and —NH—(CH2)m—C(O)—NH—(CH2)m—Rb; each Ra 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 Rb is a suitable group independently selected from the group consisting of ═O, —ORd, —OH, (C1-C3) haloalkyloxy, halogen, —CF3, —NO2, ═N2, —N3, —S(O)Rd, —S(O)2Rd, —S(O)2ORd, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Rd, —OS(O)2Rd, —OS(O)2ORd, —OS(O)2NRcRc, —C(O)Rd, —C(O)ORd, —C(O)NRcRc, OC(O)Rd, —OC(O)ORd, —OC(O)NRcRc, —OC(NH)NRcRc, —OC(NRa)NRcRc, —[NHC(O)]nRd, —[NRaC(O)]nRd, —[NHC(O)]nORd, —[NRaC(O)]nORd, —[NHC(O)]nNRcRc, —[NRaC(O)]nNRcRc, —[NHC(NH)]nNRcRc and —[NRaC(NRa)]nNRcRc; each Rc is independently hydrogen or Ra, or, alternatively, each Rc 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 Ra or suitable Rb groups; each Rd is independently hydrogen or Ra; 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 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; N2,N4-Bis(3-chloro-4-methoxy)-5-fluoro-2,4-pyrimidinediamine; or a compound in which R2 is 3,4,5-trimethoxyphenyl. 2. The compound of claim 1, wherein R4 is mono-substituted with an R8 group. 3. The compound of claim 2, wherein R4 is ortho-substituted with the R8 group. 4. The compound of claim 2, wherein R4 is meta-substituted with the R8 group. 5. The compound of claim 2, wherein R4 is para-substituted with the R8 group. 6. The compound of claim 1, wherein R5 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. The compound according to claim 1, provided R2 is not 3,4,5-tri(C1-C6)trialkoxyphenyl. 10. The compound of claim 9, wherein R4 is mono-substituted with an R8 group. 11. The compound of claim 10, wherein R4 is ortho-substituted with the R8 group. 12. The compound of claim 10, wherein R4 is meta-substituted with the R8 group. 13. The compound of claim 10, wherein R4 is para-substituted with the R8 group. 14. The compound of claim 9, wherein R5 is fluoro. 15. A pharmaceutical composition comprising a compound according to claim 9 and a pharmaceutically acceptable carrier, diluent or excipient. 16. The composition of claim 15, wherein the compound is in the form of a pharmaceutically acceptable salt.