发明名称 Compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis
摘要 The present invention discloses compounds according to Formula I:; wherein R1, R2, R3, L, and the subscript m are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions, and methods of treatment using the same, for the treatment of cystic fibrosis by administering a compound of the invention.
申请公布号 US9382254(B2) 申请公布日期 2016.07.05
申请号 US201414271080 申请日期 2014.05.06
申请人 GALAPAGOS NV 发明人 De Blieck Ann;De Munck Tom Roger Lisette;Joannesse Caroline Martine Andrée Marie;Kelgtermans Hans;Mammoliti Oscar;Menet Christel Jeanne Marie;Tricarico Giovanni Alessandro;Van der Plas Steven Emiel
分类号 C07D409/12;C07D417/12;C07D487/04;C07D333/36;C07D409/14;C07D413/12;C07D333/38 主分类号 C07D409/12
代理机构 Quarles & Brady LLP 代理人 Quarles & Brady LLP
主权项 1. A compound according to Formula I wherein R1 is H, —CH3, —CF3, or cyclopropyl; L is —NR4—; the subscript m is 0, or 1; R2 is C1-4 alkyl or C1-4 alkyl substituted with one or more independently selected R5 groups,C3-7 cycloalkyl,4-10 membered monocyclic, bridged-, spiro-, or fused bicyclic heterocycloalkyl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected Ra groups,5-6 membered monocyclic heterocycloalkenyl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected Ra groups,C6-10 mono or bicyclic aryl optionally substituted with one or more independently selected Rb, or5-10 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 Rb; R3 is C3-7 cycloalkyl optionally substituted with one or more independently selected Rc groups,4-7 membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, and S, and optionally substituted with Rc,C6-10 mono or bicyclic aryl optionally substituted with one or more independently selected Rd groups,phenyl fused to a 5-6 membered heterocycloalkyl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected Rd groups,phenyl fused to a C5-6 cycloalkyl, optionally substituted with one or more independently selected Rd groups,5-10 membered mono 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 Rd groups,5-6 membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S, fused to a 5-6 membered heterocycloalkyl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected Rd groups,5-6 membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S, fused to a C5-6 cycloalkyl comprising one or more heteroatoms independently selected from N, O, and S, and optionally substituted with one or more independently selected Rd groups,C2-6 alkenyl,C3-6 alkyl, orC1-6 alkyl substituted with one or more independently selected Re groups; R4 is C1-6 alkyl or C1-6 alkyl substituted with one or more independently selected R6 groups, orC3-7 cycloalkyl; each R5 is independently selected from halo,OH,—CN,C1-4 alkoxy,—NR8eR8f,C3-7 cycloalkyl,6 membered mono or fused bicyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S, andphenyl optionally substituted with one or more independently selected halo,C1-4 alkyl optionally substituted with one or more independently selected halo, orC1-4 alkoxy; each R6, is independently selected from halo,OH,—CN,—NR8gR8h, andC1-4 alkoxy; each Ra is selected from halo,CN,oxo,C1-4 alkyl or C1-4 alkyl substituted with one or more independently selected R7a,C1-4 alkoxy or C14 alkoxy substituted with one or more independently selected R7a,—C(═O)O—C1-4 alkyl,phenyl,5-10 membered mono, or fused bicyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, or S, and optionally substituted with one or more independently selected C1-4 alkyl, and—NR8aR8b; each Rb is selected from halo,—CN,C1-4 alkyl or C1-4 alkyl substituted with one or more independently selected R7b,C1-4 alkoxy or C1-4 alkoxy substituted with one or more independently selected R7b,—OC(═O)C1-4 alkyl, and—NR8cR8d; each Rc is selected from halo,OH,—CN,oxo,C1-4 alkyl or C1-4 alkyl substituted with one or more independently selected R7c),C1-4 alkoxy or C1-4 alkoxy substituted with one or more independently selected R7c),phenyl or phenyl substituted with one or more independently selected halo, C1-4 alkyl,C1-4 alkoxy, —CN, or —NR9aR9b), and5-6 membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, or S or N, O, or S substituted with one or more independently selected halo, C1-4 alkyl, C1-4 alkoxy, CN, —NR9cR9d; each Rd is selected from halo,—CN,—OH,C1-4 alkyl or C1-4 alkyl substituted with one or more independently selected R7d,C1-4 alkoxy or C1-4 alkoxy substituted with one or more independently selected R7d,C3-7 cycloalkyl,5-10 membered mono or fused bicyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, or S, and—NH-Phenyl; each Re is selected from halo,OH,—CN,C1-4 alkoxy or C1-4 alkoxy substituted with one or more independently selected R7e,C3-7 cycloalkyl,phenyl or phenyl with one or more independently selected halo, C1-4 alkyl, C1-4 alkoxy, CN, and —NR9eR9f, and5-6 membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from N, O, and S or N, O, and S substituted with one or more independently selected halo, C1-4 alkyl, C1-4 alkoxy, CN, and —NR9gR9h; each R7a, R7b, R7c, R7d, and R7e is independently selected from halo,OH,—CN,—NR8iR8j, andC1-4 alkoxy; each R8a, R8b, R8c, R8d, R8e, R8f, R8g, R8h, R8i, or R8j is independently selected from H, and C1-4 alkyl; each R9a, R9b, R9c, R9d, R9e, R9f, R9g, or R9h 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.
地址 Mechelen BE