MODULATORS OF THE TRANSMEMBRANE BEHAVIOR REGULATOR OF CYSTIC FIBROSIS

Abstract

Provided are cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions containing at least one such modulator, methods of treating CFTR-mediated diseases, including cystic fibrosis, by using such modulators and pharmaceutical compositions, combination compositions and therapies employing such modulators, and processes and intermediate products for manufacturing such modulators.It refers to a compound of Formula (I), tautomers thereof, deuterated derivatives of such compounds and tautomers, and pharmaceutically acceptable salts of any of the foregoing, wherein: ring A is selected from 7- and 8-membered heterocycles containing 0-2 additional heteroatoms selected from O and N, wherein ring A is substituted with 0-4 groups selected from: C3-C6 cycloalkyl, C1-C5 alkyl, 5- and 6-membered heterocycle, among others; ring B is a 9-12-membered heteroaryl group containing 1-4 heteroatoms selected from N, O, and S, wherein ring B is substituted with 1-4 groups selected from: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, among others; each X is CH and N; Z is CH and N; R1 is H, C1-C5 alkyl, C1-C5 haloalkyl, among others; each R2 is C1-C5 alkyl, C1-C5 haloalkyl, C1-C5 alkoxy, among others; each R3 is C1-C3 alkyl, C1-C3 alkoxy, OH, and halogen; n is an integer from 2 to 5; yp is an integer from zero to 3.