METTL16 inhibitors and uses thereof

A method for treating liver cancer, lymphoma, cervical cancer, pancreatic cancer, or glioblastoma in a human patient in need thereof, the method comprising:

• (i) detecting an elevated expression level of METTL16 relative to a control in a biological sample from the human patient, wherein the control is a human patient that does not have cancer, and wherein the METTL16 is expressed by the liver cancer, lymphoma, cervical cancer, pancreatic cancer, or glioblastoma;
• and
• (ii) administering an effective amount of the compound of Formula (I) or a pharmaceutically acceptable salt thereof to the human patient having the elevated expression level of METTL16 in the biological sample in step (i);
• wherein the compound of Formula (I) is:
• wherein:
• n is an integer from 0 to 6;
• R1 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR1A, —NR1AR1B, —COOR1A, —CONR1AR1B, —NO2, —SR1A, —SO3R1A, —SO4R1A, —SO2NR1AR1B, —NHNR1AR1B, —ONR1AR1B, —NHC(O)NHNR1AR1B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R1A and R1B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR2A, —NR2AR2B, —COOR2A, —CONR2AR2B, —NO2, —SR2A, —SO3R2A, —SO4R2A, —SO2NR2AR2B, —NHNR2AR2B, —ONR2AR2B, —NHC(O)NHNR2AR2B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2A and R2B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R3 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR3A, —NR3AR3B, —COOR3A, —CONR3AR3B, —NO2, —SR3A, —SO3R3A, —SO4R3A, —SO2NR3AR3B, —NHNR3AR3B, —ONR3AR3B, —NHC(O)NHNR3AR3B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R3A and R3B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R4 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR4A, —NR4AR4B, —COOR4A, —CONR4AR4B, —NO2, —SR4A, —SO3R4A, —SO4R4A, —SO2NR4AR4B, —NHNR4AR4B, —ONR4AR4B, —NHC(O)NHNR4AR4B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R4A and R4B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R5 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR5A, —NR5AR5B, —COOR5A, —CONR5AR5B, —NO2, —SR5A, —SO3RSA, —SO4R5A, —SO2NR5AR5B, —NHNR5AR5B, —ONR5AR5B, —NHC(O)NHNR5AR5B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R5A and R5B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R6 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR6A, —NR6AR6B, —COOR6A, —CONR6AR6B, —NO2, —SR6A, —SO3R6A, —SO4R6A, —SO2NR6AR6B, —NHNR6AR6B, —ONR6AR6B, —NHC(O)NHNR6AR6B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R6A and R6B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R7 is hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OR7A, —NR7AR7B, —COOR7A, —CONR7AR7B, —NO2, —SR7A, —SO3R7A, —SO4R7A, —SO2NR7AR7B, —NHNR7AR7B, —ONR7AR7B, —NHC(O)NHNR7AR7B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• R7A and R7B are each independently hydrogen, halogen, —CF3, —CBr3, —CCl3, —CI3, —CHF2, —CHBr2, —CHCl2, —CHI2, —CH2F, —CH2Br, —CH2Cl, —CH2I, —OCF3, —OCBr3, —OCCl3, —OCI3, —OCHF2, —OCHBr2, —OCHCl2, —OCHI2, —OCH2F, —OCH2Br, —OCH2Cl, —OCH2I, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.