Sumo inhibitor compounds and uses thereof

A compound of formula I or an isomer or a pharmaceutically acceptable salt thereof:

• wherein
• is selected from a single bond or double bond;
• I is 1, m is 0, and n is 0 or 1;
• M is selected from CR3R4, —NR5, C═O, O, S═O, O═S═O, and S;
• Y is selected from CR6R7, —NR8, C═O, O, S═O, O═S═O, and S;
• Z is N;
• ring A is 5-membered heteroaryl;
• wherein ring A is optionally substituted with one or more substituent groups;
• E is selected from
• R1 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, cyano, —CX13, —CHX12, —CH2X1, —OCX13, —OCH2X1, —OCHX12, —SOn1R1A, —SOv1NR1AR1B, —NHC(O)NR1AR1B, —N(O)m1, —NR1AR1B, —NHNR1AR1B, —C(O)R1A, —(O)OR1A, —C(O)NR1AR1B, —C(O)NHNR1AR1B, —OR1A, —NR1ASO2R1B, —NR1AC(O)R1B, —NR1AC(O)OR1B, —NR1AOR1B, azido, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R2 is selected from substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or
• R1 and R2 substituents join to form a substituted or unsubstituted cycloalkyl or heterocycloalkyl;
• R3 is selected from hydrogen, halogen, —CX33, —CHX32, —CH2X3, —OCX33, —OCH2X3, —OCHX32, —CN, —SOn3R3A, —SOv3NR3AR3B, —NHC(O)NR3AR3B, —N(O)m3, —NR3AR3B, —NHNR3AR3B, —C(O)R3A, —C(O)—OR3A, —C(O)NR3AR3B, —OR3A, —NR3ASO2R3B, —NR3AC(O)R3B, —NR3AC(O)OR3B, —NR3AOR3B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R4 is selected from hydrogen, halogen, —CX43, —CHX42, —CH2X4, —OCX43, —OCH2X4, —OCHX42, —CN, —SOn4R4A, —SOv4NR4AR4B, —NHC(O)NR4AR4B, —N(O)m4, —NR4AR4B, —NHNR4AR4B, —C(O)R4A, —C(O)—OR4A, —C(O)NR4AR4B, —C(O)NHNR4AR4B, —OR4A, —NR4ASO2R4B, —NR4AC(O)R4B, —NR4AC(O)OR4B, —NR4AOR4B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or
• R3 and R4 substituents join to form a substituted or unsubstituted cycloalkyl or heterocycloalkyl;
• R5 is selected from hydrogen, halogen, —CX53, —CHX52, —CH2X5, —OCX53, —OCH2X5, —OCHX52, —CN, —SOn5R5A, —SOv5NR5AR5B, —NHC(O)NR5AR5B, —N(O)m5, —NR5AR5B, —NHNR5AR5B, —C(O)R5A, —C(O)—OR5A, —C(O)NR5AR5B, —C(O)NHNR5AR5B, —OR5A, —NR5ASO2R5B, —NR5AC(O)R5B, —NR5AC(O)OR5B, —NR5AOR5B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R6 is selected from hydrogen, halogen, —CX63, —CHX62, —CH2X6, —OCX63, —OCH2X6, —OCHX62, —CN, —SOn6R6A, —SO6NR6AR6B, —NHC(O)NR6AR6B, —N(O)m6, —NR6AR6B, —NHNR6AR6B, —C(O)R6A, —C(O)OR6A, —C(O)NR6AR6B, —C(O)NHNR6AR6B, —OR6A, —NR6ASO2R6B, —NR6AC(O)R6B, —NR6AC(O)OR6B, —NR6AOR6B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R7 is selected from hydrogen, halogen, —CX73, —CHX72, —CH2X7, —OCX73, —OCH2X7, —OCHX72, —CN, —SOn7R7A, —SO7NR7AR7B, —NHC(O)NR7AR7B, —N(O)m7, —NR7AR7B, —NHNR7AR7B, —C(O)R7A, —C(O)OR7A, —C(O)NR7AR7B, —C(O)NHNR7AR7B, —OR7A, —NR7ASO2R7B, —NR7AC(O)R7B, —NR7AC(O)OR7B, —NR7AOR7B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R8 is selected from hydrogen, halogen, —CX83, —CHX82, —CH2X8, —OCX83, —OCH2X8, —OCHX82, —CN, —SO18R8A, —SO8NR8AR8B, —NHC(O)NR8AR8B, —N(O)m8, —NR8AR8B, —NHNR8AR8B, —C(O)R8A, —C(O)—OR8A, —C(O)NR8AR8B, —C(O)NHNR8AR8B, —OR8A, —NR8ASO2R8B, —NR8AC(O)R8B, —NR8AC(O)OR8B, —NR8AOR8B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R17 is selected from hydrogen, halogen, —CX173, —CHX172, —CH2X17, —OCX173, —OCH2X17, —OCHX172, —CN, —SOn11R17A, —SOv17NR17AR17B, —NHC(O)NR17AR17B, —N(O)m17, —NR17AR17B, —NHNR17AR17B, —C(O)R17A, —C(O)—OR17A, —C(O)NR17AR17B, —C(O)NHNR17AR17B, —OR17A, —NR17ASO2R17B, —NR17AC(O)R17B, —NR17AC(O)OR17B, —NR17AOR17B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R18 is selected from hydrogen, halogen, —CX183, —CHX182, —CH2X18, —OCX183, —OCH2X18, —OCHX182, —CN, —SOn18R18A, —SOv18NR18AR18B, —NHC(O)NR18AR18B, —N(O)m18, —NR18AR18B, —NHNR18AR18B, —C(O)R18A, —C(O)—OR18A, —C(O)NR18AR18B, —C(O)NHNR18AR18B, —OR18A, —NR18ASO2R18B, —NR18AC(O)R18B, —NR18AC(O)OR18B, —NR18AOR18B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or
• R17 and R18 substituents join to form a substituted or unsubstituted cycloalkyl or heterocycloalkyl;
• R19 is selected from hydrogen, halogen, —CX193, —CHX192, —CH2X19, —OCX193, —OCH2X19, —OCHX192, —CN, —SOn19R19A, —SOv19NR19AR19B, —NHC(O)NR19AR19B, —N(O)m19, —NR19AR19B, —NHNR19AR19B, —C(O)R19A, —C(O)—OR19A, —C(O)NR19AR19B, —C(O)NHNR19AR19B, —OR19A, —NR19ASO2R19B, —NR19AC(O)R19B, —NR19AC(O)OR19B, —NR19AOR19B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R20 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, —CX203, —CHX202, —CH2X20, —OCX203, —OCH2X20, —OCHX202, —CN, —SOn20R20A, —SOv20NR20AR20B, —NHC(O)NR20AR20B, —N(O)m20, —NR20AR20B, —NHNR20AR20B, —C(O)R20A, —C(O)—OR20A, —C(O)NR20AR20B, —C(O)NHNR20AR20B, —OR20A, —NR20ASO2R20B, —NR20AC(O)R20B, —NR20AC(O)OR20B, —NR20AOR20B, —N3, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or
• R17 and R20 substituents join to form a substituted or unsubstituted cycloalkyl or heterocycloalkyl;
• R21 is selected from hydrogen, halogen, —CX213, —CHX212, —CH2X21, —OCX213, —OCH2X21, —OCHX212, —CN, —SOn21R21A, —SOv21NR21AR21B, —NHC(O)NR21AR2B, —N(O)m21, —NR21AR2B, —NHNR21AR2B, —C(O)R21A, —C(O)—OR21A, —C(O)NR21AR2B, —C(O)NHNR21AR21B, —OR21A, —NR21ASO2R21B, —NR21AC(O)R21B, —NR21AC(O)OR21B, —NR21AOR21B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted and substituted or unsubstituted heteroaryl;
• R22 is selected from hydrogen, halogen, —CX223, —CHX222, —CH2X22, —OCX223, —OCH2X22, —OCHX222, —CN, —SOn22R22A, —SOv22NR22AR22B, —NHC(O)NR22AR22B, —N(O)m22, —NR22AR22B, —NHNR22AR22B, —C(O)R22A, —C(O)—OR22A, —C(O)NR22AR22B, —C(O)NHNR22AR22B, —OR22A, —NR22ASO2R22B, —NR22AC(O)R22B, —NR22AC(O)OR22B, —NR22AOR22B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• or
• R21 and R22 substituents join to form a substituted or unsubstituted cycloalkyl or heterocycloalkyl;
• R23 is selected from hydrogen, halogen, —CX233, —CHX232, —CH2X23, —OCX233, —OCH2X23, —OCHX232, —CN, —SOn23R23A, —SOv23NR23AR23B, —NHC(O)NR23AR23B, —N(O)m23, —NR23AR23B, —NHNR23AR23B, —C(O)R23A, —C(O)—OR23A, —C(O)NR23AR23B, —C(O)NHNR23AR23B, —OR23A, —NR23ASO2R23B, —NR23AC(O)R23B, —NR23AC(O)OR23B, —NR23AOR23B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R24 is selected from hydrogen, halogen, —CX243, —CHX242, —CH2X24, —OCX243, —OCH2X24, —OCHX242, —CN, —SOn24R24A, —SOv24NR24AR24B, —NHC(O)NR24AR24B, —N(O)m24, —NR24AR24B, —NHNR24AR24B, —C(O)R24A, —C(O)—OR24A, —C(O)NR24AR24B, —C(O)NHNR24AR24B, —OR24A, —NR24ASO2R24B, —NR24AC(O)R24B, —NR24AC(O)OR24B, —NR24AOR24B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R25 is selected from hydrogen, halogen, —CX253, —CHX252, —CH2X25, —OCX253, —OCH2X25, —OCHX252, —CN, —SOn25R25A, —SOv25NR25AR25B, —NHC(O)NR25AR25B, —N(O)m25, —NR25AR25B, —NHNR25AR25B, —C(O)R25A, —(O)—OR25A, —C(O)NR25AR25B, —C(O)NHNR25AR25B, —OR25A, —NR25ASO2R25B, —NR25AC(O)R25B, —NR25AC(O)OR25B, —NR25AOR25B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R26 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, —CX263, —CHX262, —CH2X26, —OCX263, —OCH2X26, —OCHX262, —CN, —SOn26R26A, —SOv26NR26AR26B, —NHC(O)NR26AR26B, —N(O)m26, —NR26AR26B, —NHNR26AR26B, —C(O)R26A, —C(O)—OR26A, —C(O)NR26AR26B, —C(O)NHNR26AR26B, —OR26A, —NR26ASO2R26B, —NR26AC(O)R26B, —NR26AC(O)OR26B, —NR26AOR26B, —N3, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R27 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, —CX273, —CHX272, —CH2X27, —OCX273, —OCH2X27, —OCHX272, —CN, —SOn27R27A, —SOv27NR27AR27B, —NHC(O)NR27AR27B, —N(O)m27, —NR27AR27B, —NHNR27AR27B, —C(O)R27A, —C(O)—OR27-A —C(O)NR27AR27B, —C(O)NHNR27AR27B, —OR27A, —NR27ASO2R27B, —NR27AC(O)R27B, —NR27AC(O)OR27B, —NR27AOR27B, —N3, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R28 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, —CX283, —CHX282, —CH2X28, —OCX283, —OCH2X28, —OCHX282, —CN, —SOn28R28A, —SOv28NR28AR28B, —NHC(O)NR28AR28B, —N(O)m28, —NR28AR28B, —NHNR28AR28B, —C(O)R28A, —C(O)—OR28-A —C(O)NR28AR28B, —C(O)NHNR28AR28B, —OR28A, —NR28ASO2R28B, —NR28AC(O)R28B, —NR28AC(O)OR28B, —NR28AOR28B, —N3 substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R29 is selected from hydrogen, halogen, —CX293, —CHX292, —CH2X29, —OCX293, —OCH2X29, —OCHX292, —CN, —SOn29R29A, —SOv29NR29AR29B, —NHC(O)NR29AR29B, —N(O)m29, —NR29AR29B, —NHNR29AR29B, —C(O)R29A, —C(O)—OR29A, —C(O)NR29AR29B, —C(O)NHNR29AR29B, —OR29A, —NR29ASO2R29B, —NR29AC(O)R29B, —NR29AC(O)OR29B, —NR29AOR29B, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R30 is selected from hydrogen, halogen, substituted or unsubstituted alkyl, —CX303, —CHX302, —CH2X30, —OCX303, —OCH2X30, —OCHX302, —CN, —SOn30R30A, —SOv30NR30AR30B, —NHC(O)NR30AR30B, —N(O)m30, —NR30AR30B, —NHNR30AR30B, —C(O)R30A C(O)OR30A, —C(O)NR30AR30B, —C(O)NHNR30AR30B, —OR30A, —NR30ASO2R30B, —NR30AC(O)R30B, —NR30AC(O)OR30B, —NR30AOR30B, —N3, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• Each R1A, R1B, R3A, R3B, R4A, R4B, R5A, R5B, R6A, R6B, R7A, R7B, R8A, R8B, R17A, R17B, R18A, R18B, R19A, R19B, R20A, R20B, R21A, R21B, R22A, R22B, R23A, R23B, R24A, R24B, R25A, R25B, R26A, R26B, R27A, R27B, R28A, R28B, R29A, R29B, R30A, and R30B is independently selected from hydrogen, —CX3, —CHX2, —CH2X, —C(O)OH, —C(O)NH2, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O)NH2, —NHSO2H, —NHC═(O)H, —NHC(O)OH, —NHOH, —OCX3, —OCHX2, —OCH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R4A and R4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R5A and R5B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R6A and R6B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R7A and R7B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R8A and R8B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R17A and R17B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R18A and R18B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R19A and R19B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R20A and R20B, substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R21A and R21B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R22A and R22B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R23A and R23B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R24A and R24B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R25A and R25B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R26A and R26B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R27A and R27B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R28A and R28B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R29A and R29B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R30A and R30B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• Each m1, m3, m4, m5, m6, m7, m8, m17, m18, m19, m20, m21, m22, m23, m24, m25, m26, m27, m28, m29, and m30 are independently 1 or 2;
• Each v1, v3, v4, v5, v6, v7, v8, v17, v18, v19, v20, v21, v22, v23, v24, v25, v26, v27, v28, v29 and v30 are independently 1 or 2;
• Each n1, n3, n4, n5, n6, n7, n8, n17, n18, n19, n20, n21, n22, n23, n24, n25, n26, n27, n28, n29 and n30 are independently an integer from 0 to 2;
• and
• Each X, X1, X3, X4, X5, X6, X7, X8, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29 and X30 are independently —Cl, —Br, —I or —F;
• provided the compound is not 1-{4-[4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1,2,3,4-tetrahydroisoquinolin-2-yl}prop-2-en-1-one;
• further provided the compound is not ethyl 2-{4-chloro-2-[2-(prop-2-enoyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]phenoxy}acetate;
• further provided the compound is not 1-(1-cyclohexyl-1,2,3,4-tetrahydroisoquinolin-2-yl)prop-2-en-1-one;
• further provided the compound is not 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)prop-2-en-1-one;
• further provided the compound is not 1-(1,2,3,4-tetrahydroisoquinolin-2-yl)prop-2-en-1-one;
• further provided the compound is not substituted 2′-(prop-2-enoyl)-3′,4′-dihydro-2′H-spiro[cyclohexane-1,1′-isoquinoline]-4-carboxylic acid;
• further provided the compound is not 1-(7-chloro-1,2,3,4-tetrahydroisoquinolin-2-yl)prop-2-en-1-one.