Inhibitors of vap-1

A compound having structural Formula (IV):

• or an alkene isomer, tautomer, or an isotopic variant thereof;
• or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
• wherein:
• X1 and X4 are independently ═N— or ═CH—;
• X5 is ═N— or —CR5—;
• X6 is ═N— or —CR6—;
• Y is a bond, —O—, —S—, —NR7—, —OCX2—, —(CH2)z2W—, —C(O)O—, or —C(O)NH—;
• W is a bond, —O—, —S—, or —NH—;
• z1 and z2 are independently an integer from 0 to 3;
• n1, n2, n5, n6, and n7 are independently an integer from 0 to 4;
• m1, m2, m5, m6, m7, v1, v2, v5, v6, and v7 are independently 1 or 2;
• L1 is a bond, —O—, —S—, —NR1L—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, or substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• R1L is hydrogen, 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;
• R1 is independently hydrogen, halogen, —CX1.13, —CHX1.12, —CH2X1.1, —CN, —SOn1R1A, —SOv1NR1BR1C, —NHNR1BR1C, —ONR1BR1C, —NHC(O)NHNR1BR1C, —NHC(O)NR1BR1C, —N(O)m1, —NR1BR1C, —C(O)R1D, —C(O)OR1D, —C(O)NR1BR1C, —OR1A, —NR1BSO2R1A, —NR1BC(O)R1D, —NR1BC(O)OR1D, —NR1BOR1D, —OCX1.13, —OCHX1.12, R12-substituted or unsubstituted alkyl, R12-substituted or unsubstituted heteroalkyl, R12-substituted or unsubstituted cycloalkyl, R12-substituted or unsubstituted heterocycloalkyl, R12-substituted or unsubstituted aryl, or R12-substituted or unsubstituted heteroaryl, or at least one amino acid;
• R2 is hydrogen, halogen, —CX2.13, —CHX2.12, —CH2X2.1, —CN, —SOn2R2A, —SOv2NR2BR2C, —NR2BR2C, —C(O)R2D, —C(O)OR2D, —C(O)NR2BR2C, —OR2A, —OCX2.13, —OCHX2.12, 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 R4 are independently hydrogen or —F;
• R5 is hydrogen, halogen, —CX5.13, —CHX5.12, —CH2X5.1, —CN, —N3, —SOn5R5A, —SOv5NR5BR5C, —NHNR5BR5C, —ONR5BR5C, —NHC(O)NHNR5BR5C, —NHC(O)NR5BR5C, —N(O)m5, —NR5BR5C, —C(O)R5D, —C(O)OR5D, —C(O)NR5BR5C, —OR5A, —NR5BSO2R5A, —NR5BC(O)R5D, —NR5BC(O)OR5D, —NR5BOR5D, —OCX5.13, —OCHX5.12, 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, —CX6.13, —CHX6.12, —CH2X6.1, —CN, —N3, —SOm6R6A, —SOv6NR6BR6C, —NHNR6BR6C, —ONE6BR6C, —NHC(O)NHNR6BR6C, —NHC(O)NR6BR6C, —N(O)m6, —NR6BR6C, —C(O)R6D, —C(O)OR6D, —C(O)NR6BR6C, —OR6A, —NR6BSO2R6A, —NR6BC(O)R6D, —NR6BC(O)OR6D, —NR6BOR6D, —OCX6.13, —OCHX6.12, 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, —CX7.13, —CHX7.12, —CH2X7.1, —CN, —SOn7R7A, —SOv7NR7BR7C, —NR7BR7C, —C(O)R7D, —C(O)OR7D, —C(O)NR7BR7C, —OCX7.13, —OCHX7.12, 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;
• R12 is hydrogen, halogen, —CX12.13, —CHX12.12, —CH2X12.1, —CN, —SOn12R12A, —SOv12NR12BR12C, —NR12BR12C, —C(O)R12D, —C(O)OR12D, —C(O)NR12BR12C, —OR12A, —OCX12.13, —OCHX12.12, 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 is hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, R12A-substituted or unsubstituted alkyl, R12A-substituted or unsubstituted heteroalkyl, R12A-substituted or unsubstituted cycloalkyl, R12A-substituted or unsubstituted heterocycloalkyl, R12A-substituted or unsubstituted aryl, or R12A-substituted or unsubstituted heteroaryl;
• R1B is hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, R12B-substituted or unsubstituted alkyl, R12B-substituted or unsubstituted heteroalkyl, R12B-substituted or unsubstituted cycloalkyl, R12B-substituted or unsubstituted heterocycloalkyl, R12B-substituted or unsubstituted aryl, or R12B-substituted or unsubstituted heteroaryl;
• R1C is hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, R12C-substituted or unsubstituted alkyl, R12C-substituted or unsubstituted heteroalkyl, R12C-substituted or unsubstituted cycloalkyl, R12C-substituted or unsubstituted heterocycloalkyl, R12C-substituted or unsubstituted aryl, or R12C-substituted or unsubstituted heteroaryl;
• or R1B and R1C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R1D is hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, R12D-substituted or unsubstituted alkyl, R12D-substituted or unsubstituted heteroalkyl, R12D-substituted or unsubstituted cycloalkyl, R12D-substituted or unsubstituted heterocycloalkyl, R12D-substituted or unsubstituted aryl, or R12D-substituted or unsubstituted heteroaryl;
• R2A, R2B, R2C, R2D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R12A, R12B, R12C, and R12D are independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, 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;
• or R2B and R2C;
• R5B and R5C;
• R6B and R6C;
• R7B and R7C;
• R8B and R8C;
• or R12B and R12C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• and
• X, X1.1, X2.1, X5.1, X6.1, X7.1, and X12.1 are independently —Cl, —Br, —I, or —F.