CFTR regulators and methods of use thereof

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein,
• L1 is —CH2—;
• R20 is substituted or unsubstituted pyridyl, furanyl, or thiophenyl;
• n1, n3, n4, n5, n6, n7, n8, and n9 are independently an integer from 0 to 4;
• m1, m2, m3, m4, m5, m6, m7, m8, m9, v1, v2, v3, v4, v5, v6, v7, v8, and v9 are independently 1 or 2;
• R1 is hydrogen, —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, 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, —CHX2.12, —CH2X2.1, —CN, —SOv2NR2BR2C, —NHNR2BR2C, —ONR2BR2C, —NHC(O)NHNR2BR2C, —NHC(O)NR2BR2C, —N(O)m2, —NR2BR2C, C(O)R2D, —C(O)NR2BR2C, —NR2BSO2R2A, —NR2BC(O)R2D, —NR2BC(O)OR2D, —NR2BOR2D, —OCX2.13, —OCHX2.12, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R3 is hydrogen, —CX3.13, —CHX3.12, —CH2X3.1, —CN, —SOn3R3A, —SOv3NR3BR3C, —NH NR3BR3C, —ONR3BR3C, —NHC(O)NHNR3BR3C, —NHC(O)NR3BR3C, —N(O)m3, —NR3BR3C, —C(O)R3D, —C(O)OR3D, —C(O)NR3BR3C, —OR3A, —NR3BSO2R3A, —NR3BC(O)R3D, —NR3BC(O)OR3D, —NR3BOR3D, —OCX3.13, —OCHX3.12, 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,
• R4 is hydrogen, —CX4.13, —CHX4.12, —CH2X4.1, —CN, —SOn4R4A, —SOv4NR4BR4C, —NHNR4BR4C, —ONR4BR4C, —NHC(O)NHNR4BR4C, —NHC(O)NR4BR4C, —N(O)m4, —NR4BR4C, —C(O)R4D, —C(O)OR4D, —C(O)NR4BR4C, —OR4A, —NR4BSO2R4A, —NR4BC(O)OR4D, —NR4BOR4D, —OCX4.13, —OCHX4.12, 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;
• R5 is hydrogen, —CX5.13, —CHX5.12, —CH2X5.1, —CN, —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)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;
• R1 and R2, R2 and R3, R3 and R4, or R1 and R5 are optionally joined to form, together with the atoms to which they are attached, 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, —SOn6R6A, —SOv6NR6BR6C, —NHNR6BR6C, —ONR6BR6C, —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, —NHNR7BR7C, —ONR7BR7C, —NHC(O)NHNR7BR7C, —NHC(O)NR7BR7C, —N(O)m7, —NR7BR7C, —C(O)R7D, —C(O)OR7D, —C(O)NR7BR7C, —OR7A, —NR7BSO2R7A, —NR7AC(O)R7C, —NR7BC(O)OR7D, —NR7BOR7D, —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;
• R8 is hydrogen, halogen, —CX8.13, —CHX8.12, —CH2X8.1, —CN, —SOn8R8A, —SOv8NR8BR8C, —NHNR8BR8C, —ONR8BR8C, —NHC(O)NHNR8BR8C, —NHC(O)NR8BR8C, —N(O)m8, —NR8BR8C, —C(O)R8D, —C(O)OR8D, —C(O)NR8BR8C, —OR8A, —NR8BSO2R8A, —NR8BC(O)R8D, —NR8BC(O)OR8D, —NR8BOR8D, —OCX8.13, —OCHX8.12, 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;
• R9 is hydrogen, halogen, —CX9.13, —CHX9.12, —CH2X9.1, —CN, —SOn9R9A, —SOv9NR9BR9C, —NHNR9BR9C, —ONR9BR9C, —NHC(O)NHNR9BR9C, —NHC(O)NR9BR9C, —N(O)m9, —NR9BR9C, —C(O)R9D, —C(O)OR9D, —C(O)NR9BR9C, —OR9A, —NR9BSO2R9A, —NR9BC(O)R9D, —NR9BC(O)OR9D, —NR9BOR9D, —OCX9.13, —OCHX9.12, 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, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8C, R8D, R9A, R9B, R9C and R9D are independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —Cl3, —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, —OCF3, —OCCl3, —OCBr3, —OCl3, —OCHF2, —OCHCl2, —OCHBr2, —OCHI2, 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;
• R1B, R1C, R2B, R2C, R3B, R3C, R4B, R4C, R5B, R5C, R6B, R6C, R7B, R7C, R8B, R8C, R8B and R9C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• X1.1, X2.1, X3.1, X4.1, X5.1, X6.1, X7.1, X8.1, X9.1 are independently —Cl, —Br, —I or —F, and
• wherein at least one of R1, R2, R3, R4 and R5 is —NO2, with the proviso that, when R3 is —NO2 and R6, R7, R8 and R9 are hydrogen, then R5 is not —NH2, or when R1 is —NO2, and R6, R7, R8 and R9 are hydrogen, then R4 is not NH2.