Methods and compositions of inhibiting DCN1-UBC12 interaction

A method for treating a cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound having a structure represented by formula:

• or a pharmaceutically acceptable salt thereof, wherein
• each of R1a, R1b, and R1c is independently hydrogen, halogen, —SF5, —NO2, —CH3, —CH2F, —CHF2, —CF3, —OCF3, —NHCH3, —N(CH3)2, (CH2)-phenyl, -(CH2)-pyridinyl, -(CH2)-pyrimidinyl, —O-phenyl, —O-pyridinyl, or —O-pyrimidinyl, provided that at least one of R1a, R1b and R1c is not hydrogen;
• or wherein R1a and R1b are optionally covalently bonded and, together with the intermediate atoms, comprise an optionally substituted 3- to 7-membered fused aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalklyl, or heterocycloalkenyl;
• and wherein R1c is hydrogen, halogen, —OH, —SCF3, —SF5, —NO2, —CH3, —CH2F, —CHF2, —CF3, —OCF3, —NHCH3, or —N(CH3)2;
• R2 is C3-C6 alkyl, —(C1-C6 alkyl)—CF3, —(C1-C6 alkyl)-C≡CH, —(C1-C3 alkyl)-cyclopropyl, —(C1-C3 alkyl)-cyclobutyl, —(C1-C3 alkyl)-cyclopentyl, —(C1-C3 alkyl)-cyclohexyl, or —SO2—(C1-C6 alkyl);
• and wherein R2 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —OH, —SCF3, —SF5, —NO2, —CH3, —CH2F, —CHF2, —CF3, —OCF3, —NHCH3, and —N(CH3)2;
• and
• R3 is Ar1 or —(C1-C3 alkyl)-Ar1;
• wherein Ar1 is phenyl independently substituted with 0, 1, 2, or 3 groups selected from halogen, —SF5, —NO2, —CH3, —CH2F, —CHF2, —CF3, —OCF3, —NHCH3, and —N(CH3)2, or is pyridinyl having a structure represented by:
• wherein each of R20a, R20b, R20c, and R20d is independently selected from hydrogen, halogen, —SF5, —NO2, —CH3, —CH2F, —CHF2, —CF3, —OCF3, —NHCH3, —N(CH3)2, —NHC(O)CH═CH2, and —(CH2)NHC(O)CH═CH2, provided that at least one of R20a, R20b, R20c, and R20d is hydrogen;
• and
• wherein the cancer is a squamous cell carcinoma.