Claims for Patent: 10,294,215

Summary for Patent: 10,294,215

Title:	Therapeutically active compounds and their methods of use
Abstract:	Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
Inventor(s):	Giovanni Cianchetta, Byron Delabarre, Janeta Popovici-Muller, Francesco G. Salituro, Jeffrey O. Saunders, Jeremy Travins, Shunqi Yan, Tao Guo, Li Zhang
Assignee:	Wuxi Apptec Co Ltd , Servier Pharmaceuticals LLC
Application Number:	US15/638,279
Patent Claims:	1. A pharmaceutical composition comprising 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-C6alkylene)-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, and a pharmaceutically acceptable carrier. 2. The composition of claim 1, wherein R1 is independently selected from hydrogen, —CH3, —CH2CH3, CH2OH, CN, or R1 and R3 are taken together to form ═O. 3. The composition of claim 1, wherein R1 and R2 are taken together to form substituted carbocyclyl or optionally substituted heterocyclyl, wherein the substituents, when present, are independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, CN, ═O, —OH, and —C(O)C1-C4 alkyl. 4. The composition of claim 1, wherein R2 is selected from: —(C1-C4 alkyl) optionally substituted with fluoro or —OH; —(C0-C4 alkylene)-O—(C1-C4 alkyl), —(C0-C2 alkylene)-N(R6)—(C1-C6 alkyl), —(C0-C2 alkylene)-Q, and —O—(C0-C2 alkylene)-Q, wherein Q is optionally substituted with up to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, ═O, —C(O)—C1-C4 alkyl, —CN, and halo. 5. The composition of claim 1, wherein ring B is selected from phenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl,and thiazolyl, wherein ring B is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C3-C6 cycloalkyl, (C0-C2 alkylene)-O—C1-C4 alky),—O—(C1-C4 alkylene)-C3-C6 cycloalkyl, —NH—S(O)2—(C1-C4 alkyl), —S(O)2—NH(C1-C4 alkyl), —S(O)2—NH—(C3-C6 cycloalkyl), —S(O)2-(saturated heterocyclyl), —CN, —S(O)2—(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl)2, —OH, C(O)—O—(C1-C4 alkyl), saturated heterocyclyl, and —NH2. 6. The composition of claim 1, wherein R1 is independently selected from hydrogen, —CH3, —CH2CH3, CH2OH, CN, or R1 and R3 are taken together to form ═O; R2 is selected from: —(C1-C4 alkyl) optionally substituted with fluoro or —OH; —(C0-C4 alkylene)-O—(C1-C4 alkyl), —(C0-C2 alkylene)-N(R6)—(C1-C6 alkyl), —(C0-C2 alkylene)-Q, and —O—(C0-C2 alkylene)-Q, wherein Q is optionally substituted with up to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, ═O, —C(O)—C1-C4 alkyl, —CN, and halo; and B is selected from phenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl,and thiazolyl, wherein ring B is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C3-C6 cycloalkyl, (C0-C2 alkylene)-O—C1-C4 alky), alkylene)-C3-C6 cycloalkyl, —NH—S(O)2—(C1-C4 alkyl), —S(O)2—NH(C1-C4 alkyl), —S(O)2—NH—(C3-C6 cycloalkyl), —S(O)2-(saturated heterocyclyl), —CN, —S(O)2—(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl)2, —OH, C(O)—O—(C1-C4 alkyl), saturated heterocyclyl, and —NH2. 7. 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. 8. The method of claim 7, wherein R1 is independently selected from hydrogen, —CH3, —CH2CH3, CH2OH, CN, or R1 and R3 are taken together to form ═O. 9. The method of claim 7, wherein R1 and R2 are taken together to form substituted carbocyclyl or optionally substituted heterocyclyl, where the substituents, when present, are independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, CN, ═O, —OH, and —C(O)C1-C4 alkyl. 10. The method of claim 7, wherein R2 is selected from: —(C1-C4 alkyl) optionally substituted with fluoro or —OH; —(C0-C4 alkylene)-O—(C1-C4 alkyl), —(C0-C2 alkylene)-N(R6)—(C1-C6 alkyl), —(C0-C2 alkylene)-Q, and —O—(C0-C2 alkylene)-Q, wherein Q is optionally substituted with up to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, ═O, —C(O)—C1-C4 alkyl, —CN, and halo. 11. The method of claim 7, wherein ring B is selected from phenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl,and thiazolyl, wherein ring B is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C3-C6 cycloalkyl, (C0-C2 alkylene)-O—C1-C4 alky), —O—(C1-4 alkylene)-C3-C6 cycloalkyl, —NH—S(O)2—(C1-C4 alkyl), —S(O)2—NH(C1-C4 alkyl), —S(O)2—NH—(C3-C6 cycloalkyl), —S(O)2-(saturated heterocyclyl), —CN, —S(O)2—(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl)2, —OH, C(O)—O—(C1-C4 alkyl), saturated heterocyclyl, and —NH2. 12. The method of claim 7, wherein R1is independently selected from hydrogen, —CH3, —CH2CH3, CH2OH, CN, or R1 and R3 are taken together to form ═O; R2 is selected from: —(C1-C4 alkyl) optionally substituted with fluoro or —OH; —(C0-C4 alkylene)-O—(C1-C4 alkyl), —(C0-C2 alkylene)-N(R6)—(C1-C6 alkyl), —(C0-C2 alkylene)-Q, and —O—(C0-C2 alkylene)-Q, wherein Q is optionally substituted with up to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, ═O, —C(O)—C1-C4 alkyl, —CN, and halo; and B is selected from phenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl,and thiazolyl, wherein ring B is optionally substituted with up to two substituents independently selected from halo, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C3-C6 cycloalkyl, (C0-C2 alkylene)-O—C1-C4 alky), —O—C1-C4 alkylene)- C3-C6 cycloalkyl, —NH—S(O)2—(C1-C4 alkyl), —S(O)2—NH(C1-C4 alkyl), —S(O)2—NH—(C3-C6 cycloalkyl), —S(O)2-(saturated heterocyclyl), —CN, —S(O)2—(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl)2, —OH, C(O)—O—(C1-C4 alkyl), saturated heterocyclyl, and —NH2. 13. The method of claim 7, wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation. 14. The method of claim 7, wherein the IDH2 mutation is an IDH2 R140Q mutation. 15. The method of claim 7, wherein the cancer is selected from glioblastoma, myelodysplastic syndrome, myeloproliferative neoplasm, acute myelogenous leukemia, sarcoma, melanoma, non small cell lung cancer, chondrosarcoma, cholangiocarcinomas or angioimmunoblastic non-Hodgkin's lymphoma. 16. The method of claim 7, wherein the cancer is acute myelogenous leukemia. 17. The method of claims 7, further comprising administering to the patient in need thereof a second therapeutic agent useful in the treatment of cancer. 18. The method of claim 17, wherein the cancer is acute myelogenous leukemia. 19. 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. 20. The method of claim 19, wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation. 21. The method of claim 19, wherein the IDH2 mutation is an IDH2 R140Q mutation. 22. The method of claim 19, wherein the cancer is selected from glioblastoma, myelodysplastic syndrome, myeloproliferative neoplasm, acute myelogenous leukemia, sarcoma, melanoma, non small cell lung cancer, chondrosarcoma, cholangiocarcinomas or angioimmunoblastic non-Hodgkin's lymphoma. 23. The method of claim 19, wherein the cancer is acute myelogenous leukemia. 24. The method of claims 19, further comprising administering to the patient in need thereof a second therapeutic agent useful in the treatment of cancer. 25. The method of claim 24, wherein the cancer is acute myelogenous leukemia. 26. 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. 27. The method of claim 26, wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation. 28. The method of claim 26, wherein the IDH2 mutation is an IDH2 R140Q mutation. 29. The method of claim 26, wherein the cancer is selected from glioblastoma, myelodysplastic syndrome, myeloproliferative neoplasm, acute myelogenous leukemia, sarcoma, melanoma, non small cell lung cancer, chondrosarcoma, cholangiocarcinomas or angioimmunoblastic non-Hodgkin's lymphoma. 30. The method of claim 26, wherein the cancer is acute myelogenous leukemia. 31. The method of claims 26, further comprising administering to the patient in need thereof a second therapeutic agent useful in the treatment of cancer. 32. The method of claim 31, wherein the cancer is acute myelogenous leukemia.