Pcna inhibitors and uses thereof

A compound, or a pharmaceutically acceptable salt thereof, having the formula:

• wherein
• L1 is —O—, —NR7—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —NR7C(O)—, —C(O)NR7—, —NR7C(O)NR8—, —NR7S(O)2O—, —OS(O)2NR7—, —NR7S(O)2—, —S(O)2NR7—, —S(O)—, —S(O)2—, —OS(O)2O—, —S(O)2O—, —OS(O)2—, —P(O)(OR7)—, —OP(O)(OR7)O—, —OP(O)(OR7)—, —P(O)(OR7)O—, or —CR8R9—;
• R7, R8, and R9 are independently hydrogen, halogen, —OH, —N3, or substituted or unsubstituted alkyl;
• Ring A is substituted or unsubstituted phenyl or substituted or unsubstituted 5 to 6 membered heteroaryl;
• R1 is independently halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCHX12, —OCH2X1, —CN, —SOn1R1D, —SOv1NR1AR1B, —NR1CNR1AR1B, —ONR1AR1B, —NHC(O)NR1CNR1AR1B, —NR1CC(O)NR1AR1B, —N(O)m1, —NR1AR1B, —C(O)R1C, —C(O)OR1C, —OC(O)R1C, —OC(O)OR1C, —C(O)NR1AR1B, —OR1D, —SR1D, —NR1ASO2R1D, —NR1AC(O)R1C, —NR1AC(O)OR1C, —OC(O)NR1AR1B, —NR1AOR1C, —P(O)R1AR1B, —N3, 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;
• two adjacent R1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 is hydrogen, halogen, —CX23, —CHX22, —CH2X2, —CN, —COOH, —CONH2, —N3, 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, —CX33, —CHX32, —CH2X3, —CN, —COOH, —CONH2, —N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or 29 unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R6 is hydrogen, halogen, —CX63, —CHX62, —CH2X6, —OCX63, —OCHX62, —OCH2X6, —CN, —SOn6R6D, —SOv6NR6AR6B, —NR6CNR6AR6B, —ONR6AR6B, —NHC(O)NR6CNR6AR6B, —NR6CC(O)NR6AR6B, —N(O)m6, —NR6AR6B, —C(O)R6C, —C(O)OR6C, —OC(O)R6C, —OC(O)OR6C, —C(O)NR6AR6B, —OR6D, —SR6D, —NR6ASO2R6D, —NR6AC(O)R6C, —NR6AC(O)OR6C, —OC(O)NR6AR6B, —NR6AOR6C, —P(O)R6AR6B, —N3, 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 and R6 may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R1A, R1B, R1C, R1D, R6A, R6B, R6C, and R6D are independently hydrogen, halogen, —CX3, —CHX2, —CH2X, —CN, —COOH, —CONH2, —N3, 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 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;
• z1 is an integer from 0 to 4;
• m1, m6, v1, and v6 are independently 1 or 2;
• n1 and n6 are independently an integer from 0 to 4;
• X, X1, X2, X3, and X6 are independently —Cl, —Br, —I, or —F;
• and
• m is an integer from 0 to 5.

A method of making compound (I), or a pharmaceutically acceptable salt thereof, said method comprising mixing compound (VII) and compound (X) together in a reaction vessel;

• wherein
• compound (I) has the formula:
• compound (VII) has the formula:
• compound (X) has the formula:
• L1 is —O—, —NR7—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —NR7C(O)—, —C(O)NR7—, —NR7C(O)NR8—, —NR7S(O)2O—, —OS(O)2NR7—, —NR7S(O)2—, —S(O)2NR7—, —S(O)—, —S(O)2—, —OS(O)2O—, —S(O)2O—, —OS(O)2—, —P(O)(OR7)—, —OP(O)(OR7)O—, —OP(O)(OR7)—, —P(O)(OR7)O—, or —CR8R9—;
• R7, R8, and R9 are independently hydrogen, halogen, —OH, —N3, or substituted or unsubstituted alkyl;
• Ring A is substituted or unsubstituted phenyl or substituted or unsubstituted 5 to 6 membered heteroaryl;
• Ring B is substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted quinolinyl, or substituted or unsubstituted isoquinolinyl;
• R1 is independently halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCHX12, —OCH2X1, —CN, —SOn1R1D, —SOv1NR1AR1B, —NR1CNR1AR1B, —ONR1AR1B, —NHC(O)NR1CNR1AR1B, —NR1CC(O)NR1AR1B, —N(O)m1, —NR1AR1B, —C(O)R1C, —C(O)OR1C, —OC(O)R1C, —OC(O)OR1C, —C(O)NR1AR1B, —OR1D, —SR1D, —NR1ASO2R1D, —NR1AC(O)R1C, —NR1AC(O)OR1C, —OC(O)NR1AR1B, —NR1AOR1C, —P(O)R1AR1B, —N3, 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;
• two adjacent R1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 is hydrogen, halogen, —CX23, —CHX22, —CH2X2, —CN, —COOH, —CONH2, —N3, 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, —CX33, —CHX32, —CH2X3, —CN, —COOH, —CONH2, —N3, 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, —CX63, —CHX62, —CH2X6, —OCX63, —OCHX62, —OCH2X6, —CN, —SOn6R6D, —SOv6NR6AR6B, —NR6CNR6AR6B, —ONR6AR6B, —NHC(O)NR6CNR6AR6B, —NR6CC(O)NR6AR6B, —N(O)m6, —NR6AR6B, —C(O)R6C, —C(O)OR6C, —OC(O)R6C, —OC(O)OR6C, —C(O)NR6AR6B, —OR6D, —SR6D, —NR6ASO2R6D, —NR6AC(O)ROC, —NR6AC(O)OR6C, —OC(O)NR6AR6B, —NR6AOR6C, —P(O)R6AR6B, —N3, 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 and R6 may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R1A, R1B, R1C, R1D, R6A, R6B, R6C, and R6D are independently hydrogen, halogen, —CX3, —CHX2, —CH2X, —CN, —COOH, —CONH2, —N3, 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 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;
• z1 is an integer from 0 to 4;
• m1, m6, v1, and v6 are independently 1 or 2;
• n1 and n6 are independently an integer from 0 to 4;
• X, X1, X2, X3, and X6 are independently —Cl, —Br, —I, or —F;
• m is an integer from 0 to 5;
• n is an integer from 0 to 10;
• and
• LG is a leaving group.