Modulators of cystic fibrosis transmembrane conductance regulator

A method of modulating CFTR activity comprising the step of contacting said CFTR with a compound of formula (VA):

• or a pharmaceutically acceptable salt or tautomer thereof, wherein:
• k is 0 or 1;
• Each R1 is independently H, halo or C1-3 alkyl;
• Each W is a bond or a C1-6 straight or branched aliphatic chain wherein up to 2 of the carbon units 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′SO7—, or —NR′SO2NR′—;
• and RW is independently R′, halo, —NO2, —CN, —CF3, or —OCF3;
• m is 0-5;
• Each R′ is hydrogen or a group selected from a C1-8 aliphatic, a 3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 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;
• and
• Each of Z1 or Z2 is independently —CH—, —CR1—, or N, and at least one of Z1 or Z2 is N.