Modulators of cystic fibrosis transmembrane conductance regulator

A compound of Formula I:

• or pharmaceutically acceptable salts thereof, wherein:
• Ar1 is a 5-6 membered aromatic monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is optionally fused to a 5-12 membered monocyclic or bicyclic, aromatic ring, wherein each ring contains 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ar1 has m substituents, each independently selected from —WRW;
• W is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of W are optionally and independently replaced by O, —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —C(O)NR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, NR′SO2—, or —NR′SO2NR′—;
• RW is independently R′, halo, NO2, CN, CF3, OCF3, an optionally substituted group selected from a C1-C8 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 7-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• m is 0-5;
• k is 0-3;
• each R1 is independently —X—RX;
• X is a bond or is an optionally substituted C1-C6 alkylidene chain wherein up to two methylene units of X are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR′—, —CONR′NR′—, —CO2—, —OCO—, —NR′CO2—, —O—, —NR′CONR′—, —OCONR′—, —NR′NR′, —NR′NR′CO—, —NR′CO—, —S—, —SO, —SO2—, —NR′—, —SO2NR′—, NR′SO2—, or —NR′SO2NR′—;
• RX is independently halo, NO2, CN, CF3, OCF3, OCH3, an optionally substituted group selected from a C1-C8 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 7-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R2 is hydrogen, halo, or a C1-C6 aliphatic group optionally substituted with —X—RX;
• R3 is hydrogen or a C1-C6 aliphatic group optionally substituted with —X—RX;
• R′ is independently selected from hydrogen, an optionally substituted group selected from a C1-C8 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 7-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R′ are taken together with the atom(s) to which they are bound to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• provided that
• when R2 is hydrogen and m is 0, Ar1 is not phenyl, pyridyl or pyrimidinyl;
• when R2 is hydrogen, m is 1, and Ar1 is phenyl or pyridyl, —WRW is not halo, —C1-C3 aliphatic, —SMe, —OC1-C3 aliphatic, —CN, —NH2 or —CONH2;
• when R2 is hydrogen, R3 is hydrogen, m is 2, Ar1 is phenyl, pyridyl or pyrimidinyl, and one instance of —WRW is halo, —CH3, —CH2CH3, or —OCH3, the second instance of —WRW is not —CH3, —CH2CH3, —OCH3, or halo;
• and
• when R2 is hydrogen, R3 is hydrogen, m is 3 and Ar1 is phenyl, all instances of —WRW are not simultaneously halo or C1-C3 aliphatic.