Phenyl amino pyrimidine compounds and uses thereof

A compound of formula Ia:

• wherein,
• Q is N;
• Z is selected from N and CR1;
• R1 is independently selected from H, halogen, R2, OR2, OH, R4, CN, CF3, (CH2)n, N(R2)2, NO2, R2R4, NR2SO2R3, COR4, CO2H, CO2R2, NR2COR3, NR2COR4, R2CN, R2OH, R2OR3 and OR5R3;
• or
• two R1 substituents together with the carbon atoms to which they are attached form an unsaturated N-containing 5- or 6-membered heterocyclyl;
• n is 1, 2 or 3;
• R2 is substituted or unsubstituted C1-4 alkyl or substituted or unsubstituted C1-4 alkylene where up to 2 carbon atoms can be optionally replaced with CO, NRY, CONRY, S, SO2 or O;
• R3 is R2, C2-4alkenyl or aryl;
• R4 is NH2, NHR2, N(R2)2, substituted or unsubstituted morpholino, substituted or unsubstituted thiomorpholino, substituted or unsubstituted thiomorpholino-1-oxide, substituted or unsubstituted thiomorpholino-1,1-dioxide, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted tetrahydrofuranyl and substituted or unsubstituted tetrahydropyranyl;
• R5 is C2-4 alkylene;
• R5 is C2-4 alkylene;
• R6-R9 are independently selected from H, RXCN, halogen, substituted or unsubstituted C1-4 alkyl, substituted or unsubstituted aryl, OR1, CO2R1, N(R1)2, NO2, CON(R1)2 and CON(R1)2, wherein at least one of R6-R9 is RXCN;
• RX is substituted or unsubstituted C1-4 alkylene wherein up to 2 carbon atoms can be optionally replaced with CO, NSO2R1, NRY, CONRY, SO, SO2, or O;
• RY is H or substituted or unsubstituted C1-4 alkyl;
• and
• R11 is selected from H, halogen, substituted or unsubstituted C1-4 alkyl, OR2, CO2R2, CN, CON(R1)2 and CF3,
• wherein the substituents are selected from the group consisting of C1-4 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylaryl, aryl, heterocyclyl, halo, haloaryl, haloheterocyclyl, hydroxy, C1-4 alkoxy, aryloxy, carboxy, amino, C1-6 alkylacyl, arylacyl, heterocycylylacyl, acylamino, acyloxy, C1-6 alkylsulphenyl, arysulphonyl and cyano, or an enantiomer thereof,
• or a pharmaceutically acceptable salt thereof.

A compound selected from

• N-(cyanomethyl)-3-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-3-methyl-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-2-methyl-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• 2-cyano-N-(3-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzyl)acetamide;
• 2-(3-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzylamino)acetonitrile;
• 2-cyano-N-(3-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)acetamide;
• 2-(3-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenylamino)acetonitrile;
• N-(cyanomethyl)-4-(2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yl)benzamide;
• N-(2-cyanopropan-2-yl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(3-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-thiomorpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-iodophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)methanesulfonamide;
• N-(cyanomethyl)-4-(2-(4-(morpholinomethyl)phenylamino)pyrimidin-4-yl)benzamide;
• N-(2-(cyanomethylamino)-2-oxoethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(4-hydroxypiperidin-1-yl)phenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(4-(hydroxymethyl)piperidin-1-yl)phenylamino)-5-methylpyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(4-(hydroxymethyl)piperidin-1-yl)phenylamino)pyrimidin-4-yl)benzamide;
• 2-cyano-N-(2-methoxy-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)acetamide;
• N-(cyanomethyl)-4-(2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-2-methoxy-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(3-hydroxypiperidin-1-yl)phenylamino)-5-methylpyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-2-methoxy-4-(5-methyl-2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(5-methoxy-2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(4-(pyrrolidin-1-yl)piperidine-1-carbonyl)phenylamino)pyrimidin-4-yl)benzamide;
• 4-(2-(4-(1-benzylpiperidin-4-yloxy)phenylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• N-(cyanomethyl)-4-(2-(6-morpholinopyridin-3-ylamino)pyrimidin-4-yl)benzamide;
• 4-(5-chloro-2-(4-morpholinophenylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• 2-cyano-N-(2-methoxy-4-(5-methyl-2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)acetamide;
• 4-(2-(4-(4-acetylpiperazin-1-yl)phenylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• N-(cyanomethyl)-4-(5-methyl-2-(4-(4-(methylsulfonamido)piperidin-1-yl)phenylamino)pyrimidin-4-yl)benzamide;
• N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)-N-(prop-2-ynyl)methanesulfonamide tosylate;
• N-(cyanomethyl)-4-(2-(4-(4-hydroxypiperidin-1-yl)phenylamino)-5-methylpyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(piperidin-4-yloxy)phenylamino)pyrimidin-4-yl)benzamide;
• ethyl 4-(4-(cyanomethylcarbamoyl)phenyl)-2-(4-morpholinophenylamino)pyrimidine-5-carboxylate;
• 4-(4-(4-(cyanomethylcarbamoyl)phenyl)pyrimidin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyridin-4-yl)benzamide;
• 4-(5-bromo-2-(4-morpholinophenylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• 5-(4-(4-(cyanomethylcarbamoyl)phenyl)pyrimidin-2-ylamino)-N,N-dimethyl-2-morpholinobenzamide;
• N-tert-butyl-5-(4-(4-(cyanomethylcarbamoyl)phenyl)pyrimidin-2-ylamino)-2-morpholinobenzamide;
• 5-(4-(4-(cyanomethylcarbamoyl)phenyl)pyrimidin-2-ylamino)-N-ethyl-2-morpholinobenzamide;
• N-(2-chloro-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)-2-cyanoacetamide;
• 2-cyano-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)-2-(trifluoromethoxy)phenyl)acetamide;
• N-(cyanomethyl)-4-(2-(4-morpholino-3-(trifluoromethyl)phenylamino)pyrimidin-4-yl)benzamide;
• 5-(4-(4-(N-(cyanomethyl)methylsulfonamido)phenyl)pyrimidin-2-ylamino)-N-(2-(dimethylamino)ethyl)-2-morpholinobenzamide;
• N-(cyanomethyl)-N-(4-(2-(4-morpholino-3-(trifluoromethyl)phenylamino)pyrimidin-4-yl)phenyl)methanesulfonamide;
• N-(cyanomethyl)-4-(2-(3-(propoxymethyl)phenylamino)pyrimidin-4-yl)benzamide;
• 2-cyano-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)-2-(trifluoromethyl)phenyl)acetamide;
• 4-(2-(1H-indazol-5-ylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• N-(1-cyanocyclopropyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• 4-(2-(3-(allyloxymethyl)-4-morpholinophenylamino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(1-ethylpiperidin-4-yloxy)phenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-N-(4-(2-(3-fluoro-4-morpholinophenylamino)pyrimidin-4-yl)phenyl)methanesulfonamide;
• N-(4-(2-(3-cyano-4-morpholinophenylamino)pyrimidin-4-yl)phenyl)-N-(cyanomethyl)methanesulfonamide;
• 2-cyano-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)acetamide;
• 5-(4-(4-(N-(cyanomethyl)methylsulfonamido)|phenyl)pyrimidin-2-ylamino)-2-morpholinobenzoic acid;
• N-(cyanomethyl)-4-(2-(4-(3-(diethylamino)propoxy)phenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-(4-(2-morpholinoethoxy)phenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(2-{[4-(1,1-dioxo-1λ6,4-thiomorpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-[2-({4-[(1,1-dioxo-1λ6,4-thiomorpholin-4-yl)methyl]phenyl}amino)pyrimidin-4-yl]benzamide;
• N-(cyanomethyl)-N-methyl-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• N-(cyanomethyl)-4-(5-methyl-2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide;
• and
• N-(cyanomethyl)-4-(5-fluoro-2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide or a pharmaceutically acceptable salt thereof.