Therapeutically active compounds and their methods of use

A method of treating a cancer characterized by the presence of an IDH2 mutation, wherein the IDH2 mutation results in a new ability of the enzyme to catalyze the NADPH dependent reduction of α ketoglutarate to R(-) 2 hydroxyglutarate in a patient, comprising the step of administering to the patient in need thereof a compound having formula I or a pharmaceutically acceptable salt or hydrate thereof:

• wherein:
• ring A is selected from phenyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, and thiazolyl, wherein ring A is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, —NH—S(O)2—C1-C4 alkyl, —S(O)2—NH(C1-C4 alkyl), CN, S(O)2-C1-C4 alkyl, C1-C4 alkoxy, NH(C1-C4 alkyl), —OH, and —NH2;
• ring B is an optionally substituted 5-6 member monocyclic aryl or monocyclic heteroaryl;
• R1 and R3 are each independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, —O—C1-C4 alkyl, and CN, wherein any alkyl portion of R1 is optionally substituted with —OH, NH2, NH(C1-C4 alkyl), or N(C1-C4 alkyl)2;
• R2 is selected from:
• —(C1-C6 alkyl), —(C2-C6 alkenyl or alkynyl), —(C1-C6 alkylene)-N(R6)—(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)(R6),—(C1-C6 alkylene)-N(R6)—S(O)1-2—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—S(O)1-2—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-S(O)1-2—N(R6)(R6), —(C1-C4 alkylene)-S(O)1-2—N(R6)—(C1-C6 alkylene)-Q, —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-S(O)0-2—(C1-C6 alkyl), —(C0-C6 alkylene)-S(O)0-2—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)—C(O)—N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-Q, wherein:
• any alkyl or alkylene moiety present in R2 is optionally substituted with one or more —OH, —O(C1-C4 alkyl) or halo;
• any terminal methyl moiety present in R2 is optionally replaced with —CH2OH, CF3, —CH2F, —CH2Cl, C(O)CH3, C(O)CF3, CN, or CO2H;
• each R6 is independently selected from hydrogen and C1-C6 alkyl;
• and
• Q is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl, any of which is optionally substituted;
• or
• R1 and R3 are optionally taken together with the carbon to which they are attached to form C(═O), or
• R1 and R2 are optionally taken together to form substituted carbocyclyl, or optionally substituted heterocyclyl, wherein:
• (a) when ring A is unsubstituted phenyl, and ring B is phenyl substituted by methoxy or ethoxy;
• then said phenyl of ring B is not further substituted by oxazolyl;
• (b) when ring A is optionally substituted phenyl or optionally substituted pyridyl and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)-aryl;
• (c) when ring A is optionally substituted phenyl, and ring B is optionally substituted phenyl or pyrrolyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)C(O)NH2;
• (d) when ring A is phenyl substituted with 2 hydroxyl or methoxy, and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH-cycloheptyl;
• (e) when ring A is optionally substituted phenyl and ring B is optionally substituted phenyl;
• then R1 and R2 do not form 2,2,6,6-tetramethylpiperidin-4-yl;
• (f) when ring A and ring B are optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not cysteine, optionally substituted phenylalanine or leucine;
• or methyl ester thereof;
• (g) when ring A is phenyl or pyridin-3-yl optionally substituted with one or more substituents selected from halo, methyl or CF3, and ring B is phenyl optionally substituted with one or more substituents selected from halo, methyl or CF3, methoxy, or CH═C(phenyl)CN;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is other than —NH(C1-C8 alkylene)-N(Ra)(Ra), —NH-1-(aminomethyl)cyclopentylmethyl, —NH-4-(aminomethyl)cyclohe xylmethyl, wherein each Ra is hydrogen, C1-C4 alkyl or two Ras are taken together with the nitrogen to which they are commonly bound to form morpholin-4-yl or piperidin-1-yl;
• (h) when ring A is phenyl, 4-chlorophenyl or 4-methylphenyl and ring B is 4-chlorophenyl or 3,4-dichlorophenyl;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is not —NH-isopropyl;
• (i) when ring A is unsubstituted phenyl and the portion of the compound represented by —NHC(R1)(R2)(R3) is —NH—CH2CH2N(CH3)2, —NH—CH2CH2-morpholin-4-yl or —NH—CH2CH2OH;
• then ring B is other than oxadiazole, imidazole, thiazole or oxazole each of which is substituted with —C(O)NHRb, wherein Rb is isopropyl, cyclopropyl or 2-chloro-6-methylphenyl;
• and
• (j) the compound is other than:
• (E)-3-(4-((4-((3-(diethylamino)propyl)amino)-6-phenyl-1,3,5-triazin-2-yl)amino)-2-methoxyphenyl)-2-phenylacrylonitrile,
• 4-((4-((furan-2-ylmethyl)amino)-6-(pyridin-4-yl)-1,3,5-triazin-2-yl)amino)phenol,
• 3-(4-((5 -aminopentyl)amino)-6-((3-fluorophenyl)amino)-1,3,5-triazin-2-yl)phenol,
• N2,6-bis(3-fluorophenyl)-N4-(piperidin-3-yl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-6-phenyl-N4-(p-tolyl)-1,3,5-triazine-2,4-diamine,
• N2-cyclohexyl-N4,6-diphenyl-1,3,5-triazine-2,4-diamine,
• (R)-3-((4-(3-chlorophenyl)-6-(pyrrolidin-3-ylamino)-1,3,5-triazin-2-yl)amino)-4-methylbenzamide,
• 2-chloro-4-(methylsulfonyl)-N-[4-(phenylamino)-6-(2-pyridinyl)-1,3,5,-triazin-2-yl]-benzamide,
• N2-(2-methoxyethyl)-N4-phenyl-6-[5-[6-(2,2,2-trifluoroethoxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl]1,3,5-triazine-2,4-diamine,
• N2-(2-furanylmethyl)-6-phenyl-N4-[3-(trifluoromethyl)phenyl]-1,3,5-triazine-2,4-diamine,
• 6-(3-methoxyphenyl)-N2-methyl-N4-(3-nitrophenyl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-N4-(4-methylphenyl)-6-phenyl-1,3,5-triazine-2,4-diamine, and
• 4-[4-(5-chloro-2-methylphenyl)-6-(methylamino)-1,3,5-triazin-2-yl]amino-benzenemethanol.

A method of treating a cancer characterized by the presence of an IDH2 mutation, wherein the IDH2 mutation results in a new ability of the enzyme to catalyze reduction of α ketoglutarate to R(−) 2 hydroxyglutarate in a patient, comprising the step of administering to the patient in need thereof a compound having formula I or a pharmaceutically acceptable salt or hydrate thereof:

• wherein:
• ring A is selected from phenyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, and thiazolyl, wherein ring A is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, —NH—S(O)2—C1-C4 alkyl, —S(O)2—NH(C1-C4 alkyl), CN, S(O)2—C1-C4 alkyl, C1-C4 alkoxy, NH(C1-C4 alkyl), —OH, and —NH2;
• ring B is an optionally substituted 5-6 member monocyclic aryl or monocyclic heteroaryl;
• R1 and R3 are each independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, —O—C1-C4 alkyl, and CN, wherein any alkyl portion of leis optionally substituted with —OH, NH2, NH(C1-C4 alkyl), or N(C1-C4 alkyl)2;
• R2 is selected from:
• —(C1-C6 alkyl), —(C2-C6 alkenyl or alkynyl), —(C1-C6 alkylene)-N(R6)—(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)(R6), —(C1-C6 alkylene)-N(R6)—S(O)1-2—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—S(O)1-2—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-S(O)1-2—N(R6)(R6), —(C1-C4 alkylene)-S(O)1-2—N(R6)—(C1-C6 alkylene)-Q, —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-S(O)0-2—(C1-C6 alkyl), —(C0-C6 alkylene)-S(O)0-2—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)-C(O)—N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-Q, wherein:
• any alkyl or alkylene moiety present in R2 is optionally substituted with one or more —OH, —O(C1-C4 alkyl) or halo;
• any terminal methyl moiety present in R2 is optionally replaced with —CH2OH, CF3, —CH2F, —CH2Cl, C(O)CH3, C(O)CF3, CN, or CO2H;
• each R6 is independently selected from hydrogen and C1—C6 alkyl;
• and
• Q is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl, any of which is optionally substituted;
• or
• R1 and R3 are optionally taken together with the carbon to which they are attached to form C(═O), or
• R1 and R2 are optionally taken together to form substituted carbocyclyl, or optionally substituted heterocyclyl, wherein:
• (a) when ring A is unsubstituted phenyl, and ring B is phenyl substituted by methoxy or ethoxy;
• then said phenyl of ring B is not further substituted by oxazolyl;
• (b) when ring A is optionally substituted phenyl or optionally substituted pyridyl and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)-aryl;
• (c) when ring A is optionally substituted phenyl, and ring B is optionally substituted phenyl or pyrrolyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)C(O)NH2;
• (d) when ring A is phenyl substituted with 2 hydroxyl or methoxy, and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH—cycloheptyl;
• (e) when ring A is optionally substituted phenyl and ring B is optionally substituted phenyl;
• then R1 and R2 do not form 2,2,6,6-tetramethylpiperidin-4-yl;
• (f) when ring A and ring B are optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not cysteine, optionally substituted phenylalanine or leucine;
• or methyl ester thereof;
• (g) when ring A is phenyl or pyridin-3-yl optionally substituted with one or more substituents selected from halo, methyl or CF3, and ring B is phenyl optionally substituted with one or more substituents selected from halo, methyl or CF3, methoxy, or CH═C(phenyl)CN;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is other than —NH(C1-C8 alkylene)-N(Ra)(Ra), —NH—1-(aminomethyl)cyclopentylmethyl, —NH—4-(aminomethyl)cyclohe xylmethyl, wherein each Ra is hydrogen, C1-C4 alkyl or two Ras are taken together with the nitrogen to which they are commonly bound to form morpholin-4-yl or piperidin-1-yl;
• (h) when ring A is phenyl, 4-chlorophenyl or 4-methylphenyl and ring B is 4-chlorophenyl or 3,4-dichlorophenyl;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is not —NH—isopropyl;
• (i) when ring A is unsubstituted phenyl and the portion of the compound represented by —NHC(R1)(R2)(R3) is —NH—CH2CH2N(CH3)2, —NH—CH2CH2-morpholin-4-yl or —NH—CH2CH2OH;
• then ring B is other than oxadiazole, imidazole, thiazole or oxazole each of which is substituted with —C(O)NHRb, wherein Rb is isopropyl, cyclopropyl or 2-chloro-6-methylphenyl;
• and
• (j) the compound is other than:
• (E)-3-(4-((4-((3-(diethylamino)propyl)amino)-6-phenyl-1,3,5-triazin-2-yl)amino)-2-methoxyphenyl)-2-phenylacrylonitrile,
• 4-((4-((furan-2-ylmethyl)amino)-6-(pyridin-4-yl)-1,3,5-triazin-2-yl)amino)phenol,
• 3-(4-((5-aminopentyl)amino)-6((3-fluorophenyl)amino)-1,3,5-triazin-2-yl)phenol,
• N2,6-bis(3-fluorophenyl)-N4-(piperidin-3-yl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-6-phenyl-N4-(p-tolyl)-1,3,5-triazine-2,4-diamine,
• N2-cyclohexyl-N4,6-diphenyl-1,3,5-triazine-2,4-diamine,
• (R)-3-((4-(3-chlorophenyl)-6-(pyrrolidin-3-ylamino)-1,3,5-triazin-2-yl)amino)-4-methylbenzamide,
• 2-chloro-4-(methylsulfonyl)-N-[4-(phenylamino)-6-(2-pyridinyl)-1,3,5,-triazin-2-yl]-benzamide,
• N2-(2-methoxyethyl)-N4-phenyl-6-[5-[6-(2,2,2-trifluoroethoxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl]1,3,5-triazine-2,4-diamine,
• N2-(2-furanylmethyl)-6-phenyl-N4-[3-(trifluoromethyl)phenyl]-1,3,5-triazine-2,4-diamine,
• 6-(3-methoxyphenyl)-N2-methyl-N4-(3-nitrophenyl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-N4-(4-methylphenyl)-6-phenyl-1,3,5-triazine-2,4-diamine, and
• 4-[4-(5-chloro-2-methylphenyl)-6-(methylamino)-1,3,5-triazin-2-yl]amino-benzenemethanol.

A method of treating a cancer characterized by the presence of an IDH2 mutation in a patient, comprising the step of administering to the patient in need thereof a compound having formula I or a pharmaceutically acceptable salt or hydrate thereof:

• wherein:
• ring A is selected from phenyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, and thiazolyl, wherein ring A is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, —NH—S(O)2—C1-C4 alkyl, —S(O)2—NH(C1-C4 alkyl), CN, S(O)2—C1-C4 alkyl, C1-C4 alkoxy, NH(C1-C4 alkyl), —OH, and —NH2;
• ring B is an optionally substituted 5-6 member monocyclic aryl or monocyclic heteroaryl;
• R1 and R3 are each independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, —O—C1-C4 alkyl, and CN, wherein any alkyl portion of R1 is optionally substituted with —OH, NH2, NH(C1-C4 alkyl), or N(C1-C4 alkyl)2;
• R2 is selected from:
• —(C1-C6 alkyl), —(C2-C6 alkenyl or alkynyl), —(C1-C6 alkylene)-N(R6)—(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)(R6), —(C1-C6 alkylene)-N(R6)—S(O)1-2—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)—S(O)1-2—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-S(O)1-2—N(R6)(R6), —(C1-C4 alkylene)-S(O)1-2—N(R6)—(C1-C6 alkylene)-Q, —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —C(O)N(R6)—(C1-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkyl)-Q, —(C1-C6 alkylene)-O—(C1-C6 alkyl), —(C1-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-O—(C1-C6 alkylene)-Q, —(C1-C6 alkylene)-O—C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-O—C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)N(R6)—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-N(R6)C(O)—(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-S(O)0-2—(C1-C6 alkyl), —(C0-C6 alkylene)-S(O)0-2—(C0-C6 alkylene)-Q, —(C1-C6 alkylene)-N(R6)-C(O)—N(R6)—(C1-C6 alkyl), —(C0-C6 alkylene)-Q, —(C0-C6 alkylene)-C(O)—(C1-C6 alkyl), —(C0-C6 alkylene)-C(O)—(C0-C6 alkylene)-Q, wherein:
• any alkyl or alkylene moiety present in R2 is optionally substituted with one or more —OH, —O(C1-C4 alkyl) or halo;
• any terminal methyl moiety present in R2 is optionally replaced with —CH2OH, CF3, —CH2F, —CH2Cl, C(O)CH3, C(O)CF3, CN, or CO2H;
• each R6 is independently selected from hydrogen and C1-C6 alkyl;
• and
• Q is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl, any of which is optionally substituted;
• or
• R1 and R3 are optionally taken together with the carbon to which they are attached to form C(═O), or
• R1 and R2 are optionally taken together to form substituted carbocyclyl, or optionally substituted heterocyclyl, wherein:
• (a) when ring A is unsubstituted phenyl, and ring B is phenyl substituted by methoxy or ethoxy;
• then said phenyl of ring B is not further substituted by oxazolyl;
• (b) when ring A is optionally substituted phenyl or optionally substituted pyridyl and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)-aryl;
• (c) when ring A is optionally substituted phenyl, and ring B is optionally substituted phenyl or pyrrolyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH(CH2)C(O)NH2;
• (d) when ring A is phenyl substituted with 2 hydroxyl or methoxy, and ring B is optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not —NH—cycloheptyl;
• (e) when ring A is optionally substituted phenyl and ring B is optionally substituted phenyl;
• then R1 and R2 do not form 2,2,6,6-tetramethylpiperidin-4-yl;
• (f) when ring A and ring B are optionally substituted phenyl;
• then the portion of the compound represented by —NH—C(R1)(R2)(R3) is not cysteine, optionally substituted phenylalanine or leucine;
• or methyl ester thereof;
• (g) when ring A is phenyl or pyridin-3-yl optionally substituted with one or more substituents selected from halo, methyl or CF3, and ring B is phenyl optionally substituted with one or more substituents selected from halo, methyl or CF3, methoxy, or CH═C(phenyl)CN;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is other than —NH(C1-C8 alkylene)-N(Ra)(Ra), —NH—1-(aminomethyl)cyclopentylmethyl, —NH—4-(aminomethyl)cyclohe xylmethyl, wherein each Ra is hydrogen, C1-C4 alkyl or two Ras are taken together with the nitrogen to which they are commonly bound to form morpholin-4-yl or piperidin-1-yl;
• (h) when ring A is phenyl, 4-chlorophenyl or 4-methylphenyl and ring B is 4-chlorophenyl or 3,4-dichlorophenyl;
• then the portion of the compound represented by —NHC(R1)(R2)(R3) is not —NH—isopropyl;
• (i) when ring A is unsubstituted phenyl and the portion of the compound represented by —NHC(R1)(R2)(R3) is —NH—CH2CH2N(CH3)2, —NH—CH2CH2-morpholin-4-yl or —NH—CH2CH2OH;
• then ring B is other than oxadiazole, imidazole, thiazole or oxazole each of which is substituted with -C(O)NHRb, wherein Rb is isopropyl, cyclopropyl or 2-chloro-6-methylphenyl;
• and
• (j) the compound is other than:
• (E)-3-(4-((4-((3-(diethylamino)propyl)amino)-6-phenyl-1,3,5-triazin-2-yl)amino)-2-methoxyphenyl)-2-phenylacrylonitrile,
• 4-((4-((furan-2-ylmethyl)amino)-6-(pyridin-4-yl)-1,3,5-triazin-2-yl)amino)phenol,
• 3-(4-((5-aminopentyl)amino)-6-((3-fluorophenyl)amino)-1,3,5-triazin-2-yl)phenol,
• N2,6-bis(3-fluorophenyl)-N4-(piperidin-3-yl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-6-phenyl-N4-(p-tolyl)-1,3,5-triazine-2,4-diamine,
• N2-cyclohexyl-N4,6-diphenyl-1,3,5-triazine-2,4-diamine,
• (R)-3-((4-(3-chlorophenyl)-6-(pyrrolidin-3-ylamino)-1,3,5-triazin-2-yl)amino)-4-methylbenzamide,
• 2-chloro-4-(methylsulfonyl)-N-[4-(phenylamino)-6-(2-pyridinyl)-1,3,5,-triazin-2-yl]-benzamide,
• N2-(2-methoxyethyl)-N4-phenyl-6-[5[-6-(2,2,2-trifluoroethoxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl]1,3,5-triazine-2,4-diamine,
• N2-(2-furanylmethyl)-6-phenyl-N4[3-(trifluoromethyl)phenyl]-1,3,5-triazine-2,4-diamine,
• 6-(3-methoxyphenyl)-N2-methyl-N4-(3-nitrophenyl)-1,3,5-triazine-2,4-diamine,
• N2-butyl-N4-(4-methylphenyl)-6-phenyl-1,3,5-triazine-2,4-diamine, and
• 4-[4-(5-chloro-2-methylphenyl)-6-(methylamino)-1,3,5-triazin-2-yl]amino-benzenemethanol.