NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CYSTIC FIBROSIS

摘要

The present invention discloses compounds according to Formula I:;;wherein R1 is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.

主权项

1) A compound according to Formula Iwherein
R1 is
C3-7 mono or spirocyclic cycloalkyl, optionally substituted with one or more independently selected R2 groups,4-7 membered mono or spirocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N, and S, substituted with one or more independently selected R2 groups,C6-10 monocyclic or bicyclic aryl optionally substituted with one or more independently selected R3 groups,5-10 membered monocyclic or fused bicyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected R3 groups, orC1-6 alkyl optionally substituted with one or more independently selected R4 groups, each R2 is selected from
halo,OH,—CN,—OC(═O)C1-4 alkyl,—C(═O)—C1-4 alkoxy,oxo,C1-4 alkyl (optionally substituted with one or more independently selected R5a), andC1-4 alkoxy (optionally substituted with one or more independently selected R5a), each R3 is selected from
halo,—OH,—CN,C1-4 alkyl (optionally substituted with one or more independently selected R5b),C1-4 alkoxy (optionally substituted with one or more independently selected R5b),C2-4 alkenyl (optionally substituted with one or more independently selected R5b),C3-7 cycloalkyl,4-7 membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from N, O, and S,4-7 membered monocyclic heterocycloalkenyl comprising one or more heteroatoms independently selected from N, O, and S,5-10 membered monocyclic or fused bicyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S, and—NHSO2—C1-4 alkyl; each R4 is selected from
halo,OH,C3-7 monocyclic cycloalkyl,—CN, andC1-4 alkoxy (optionally substituted with one or more independently selected R5c), each R5a, R5b, and R5c is independently selected from
halo,OH,—OP(═O)2OH,—CN,—NR6aR6b, andC1-4 alkoxy; and each R6a, or R6b is independently selected from H, and C1-4 alkyl; or a pharmaceutically acceptable salt, or a solvate, or a pharmaceutically acceptable salt of a solvate thereof.