Pyrimidine derivatives used as itk inhibitors

A compound of formula (I):

• wherein
• R1 is hydrogen, —CR7R8R9, —CH2OR24, —CH2NR25R26 or —CH2-6-membered heteroaryl wherein the 6-membered heteroaryl contains one or two nitrogen atoms and is optionally substituted by one or two substituents independently selected from C1-6alkyl and —OH;
• R2 is hydrogen or methyl;
• R3 is C1-6alkyl substituted by —OH or —NH2,
• C3-6cycloalkyl substituted by C1-6alkyl, —OH, —NR27R28, —CO2H or —CONH2,
• —(CH2)m6-membered heterocyclyl wherein the 6-membered heterocyclyl contains one or two heteroatoms independently selected from nitrogen and oxygen and is optionally substituted by —SO2CH3 or C1-6alkyl optionally substituted by —CO2H,
• naphthyl substituted by —CO2H, or
• —(CH2)nphenyl wherein the phenyl is substituted by one or two substituents independently selected from −OR10, —SR11, halo, —CO2H, —SO2NHR12, C1-6alkyl optionally substituted by —OH, —CO2H or —CONR13R14, C2-6alkenyl optionally substituted by —CO2H and C3-6cycloalkyl optionally substituted by —CO2H;
• R4 is hydrogen, —OR15, halo, —CF3, —CN, —NO2, —NR16R17, —CO2R18, —SO2CH3, —NHSO2CH3, C1-6alkyl optionally substituted by —OH, —CN, —CO2R19 or —CONH2, pyridinyl optionally substituted by —OR29, —CH2NR30R31 or —CN, or 5-membered heteroaryl wherein the 5-membered heteroaryl contains one or two heteroatoms independently selected from oxygen and nitrogen and is optionally substituted by C1-6alkyl;
• R5 and R6 are each independently hydrogen or fluoro;
• R7 and R8 are both hydrogen, or R7 and R8 are both fluoro;
• R9 is hydrogen, C1-6alkyl, or phenyl optionally substituted by fluoro;
• R10 is hydrogen or C1-6alkyl optionally substituted by —CO2R20;
• R11 is C1-6alkyl optionally substituted by —CO2H;
• R12 is hydrogen or —COC1-6alkyl;
• R13 and R14 are each independently hydrogen or C1-6alkyl optionally substituted by —OH, or
• R13 and R14, together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl optionally containing an oxygen atom;
• R15, R21 and R22 are each independently C1-6alkyl;
• R16 and R17 are each independently hydrogen, —COR21, —CO2R22, or C1-6alkyl optionally substituted by one or two —OH groups, or R16 and R17, together with the nitrogen atom to which they are attached, are linked to form a 4-, 5- or 6-membered heterocyclyl wherein the 4-membered heterocyclyl is optionally substituted by oxo and the 5- or 6-membered heterocyclyl optionally contains an oxygen atom, a sulphur atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from oxo, —OH, —NH2 and C1-6alkyl optionally substituted by —OH or —NH2;
• R18, R19, R20, R24, R32, R33, R36, R37, R38, R39, R40, R41, R42 and R43 are each independently hydrogen or C1-6alkyl;
• R23 is hydrogen or halo;
• R25 is hydrogen or C1-6alkyl optionally substituted by —OR32 and R26 is C1-8alkyl optionally substituted by —OR33, —NR34R35 or —CF3, or 5- or 6-membered heterocyclyl wherein the 5- or 6-membered heterocyclyl contains a heteroatom selected from oxygen, sulphur and nitrogen and is optionally substituted by one or two oxo substituents, or R25 and R26, together with the nitrogen atom to which they are attached, are linked to form a 4-, 5- or 6-membered heterocyclyl wherein the 4-membered heterocyclyl is optionally substituted by one or two substituents independently selected from halo and the 5- or 6-membered heterocyclyl optionally contains an oxygen atom, a sulphur atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from oxo, C1-6alkyl optionally substituted by —OR36, halo, —OR37 and —CO2R38;
• R27 and R28 are each hydrogen, or R27 and R28, together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl wherein the 6-membered heterocyclyl optionally contains an oxygen atom;
• R29 is tetrahydropyran, or C1-6alkyl optionally substituted by —OR39 or —NR40R41;
• R30 is hydrogen and R31 is C1-6alkyl optionally substituted by —OR42, or R30 and R31, together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl wherein the 6-membered heterocyclyl optionally contains an oxygen atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from C1-6alkyl;
• R34 is hydrogen or C1-6alkyl and R35 is —CO2R43, or R34 and R35, together with the nitrogen atom to which they are attached, are linked to form a 5- or 6-membered heterocyclyl wherein the 5- or 6-membered heterocyclyl optionally contains an oxygen atom or a sulphur atom and is optionally substituted by one or two oxo substituents;
• X is —N— or —CR23—;
• and
• m and n are each independently 0, 1, 2 or 3;
• or a salt thereof.