Complement Pathway Modulators and Uses Thereof

摘要

The present invention provides a compound of formula I a method for manufacturing the compounds of the invention, and its therapeutic uses as inhibitor of the complement alternative pathway and particularly as inhibitor of Factor B for the treatment of e.g. age-related macular degeneration and diabetic retinopathy. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.;

主权项

1. A compound according to Formula I or salt or stereoisomer thereof, wherein R1 is hydrogen or halogen R2 is C1-C4alkyl; R3 is hydrogen, C1-C6alkyl, C1-C4alkoxyC1-C4alkyl, or haloC1-C4alkyl; R4 is halogen, cyano or hydrogen, wherein at least one of R1 and R4 is not hydrogen; R5 is independently selected at each occurrence from hydrogen, C1-C6alkyl, C1-C4alkoxyC1-C4alkyl, phenyl, and C3-C6cycloalkyl; k is 0-3; R6 is CH2CHR7R8, or R6 is CH═CHR9, wherein R9 is C3-C6cycloalkyl or phenyl optionally substituted with 0, 1, or 2 groups independently selected from halogen, C1-C4alkyl, C1-C4alkoxy, halo C1-C4alkyl or cyano; or R6 is bicyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from N, O or S, partially unsaturated carbocycle or partially unsaturated heterocycle having 1 or 2 ring heteroatoms independently selected from N, O or S, each of which is optionally substituted with 0 to 3 substituents independently selected from amino, halogen, cyano, hydroxy, C1-C4alkyl or C1-C4alkoxy; or R6 is CH2heterocycle having 4 to 7 ring atoms and 1 or 2 ring heteroatoms selected from N, O or S, which is optionally substituted with 0, 1, or 2 groups independently selected from phenyl, halogen and C1-C6alkyl, or two substituents, taken in combination form a benzo ring optionally substituted with halogen; R7 is (CH2)pNR10R11 or C(O)NRA2, wherein RA is independently selected at each occurrence from hydrogen and C1-C4alkyl, or NRA2 taken in combination form a 4-6 member azacycle; p is 0 or 1; R8 is C1-C6alkyl, C3-C6cycloalkyl; or R8 is phenyl optionally substituted with 0-2 R12; or R8 is a 5 or 6 member heteroaryl having 1 or 2 ring heteroatoms selected from N, O and S and optionally substituted with 0-2 R13 groups; R10 is hydrogen or C1-C4alkyl; R11 is hydrogen, optionally substituted C1-C6alkyl or C1-C6haloalkyl, wherein the optional substituents are selected from C1-C4alkoxy, C3-C6cycloalkyl and 4-6 member heterocycle having 1-2 ring heteroatoms selected from N, O and S; or NR10R11, taken in combination form a 4 to 7 member saturated azacycle optionally substituted with 0, 1, or 2 C1-C4alkyl groups; R12 is independently selected at each occurrence from hydrogen, cyano, hydroxy, halogen, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4haloalkyl or C1-C4alkoxy; R13 is independently selected at each occurrence from hydrogen, C1-C4alkyl, or halogen.