Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof

A method of treating a subject suffering from a disorder or disease mediated by activation of the complement alternative pathway, wherein the disease or disorder is selected from the group consisting of age-related macular degeneration, diabetic retinopathy, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, asthma, and glomerulonephritis, wherein the method comprises administering to the subject a therapeutically effective amount of the compound, of salt or tautomer thereof, of Formula (I):

• Wherein
• n is 0, 1 or 2;
• R is hydrogen, C1-C4alkyl, or hydroxyC1-C4alkyl;
• R1 is halogen, hydroxy, C1-C6alkyl, C2-C6alkenyl, C3-C6cycloalkyl, C1-C6alkoxy, haloC1-C6alkyl, hydroxyC1-C6alkyl, aminoC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxy, C3-C6cycloalkylC1-C6alkoxy, haloC1-C6alkoxy, —S(O)pC1-C6alkyl, —CH2NHC(O)C1-C4alkyl or —OCH2C(O)R7,
• p is 0, 1, or 2;
• R2 is C1-C6alkyl, C1-C6alkoxy, hydroxyC1-C6alkyl or halogen;
• R3 is hydrogen, halogen, cyano, C1-C4alkyl, haloC1-C4alkyl, —CH2C(O)R7, phenyl or 5 or 6 member heteroaryl having 1, 2 or 3 ring heteroatoms independently selected from N, O or S, wherein the phenyl or heteroaryl is optionally substituted with 0, 1, or 2 C1-C4alkyl groups, and wherein alkyl and haloalkyl optionally substituted with 0 or 1 hydroxy;
• R4 is phenyl, naphthyl or heteroaryl, where the heteroaryl is a five or six member heteroaryl having 1, 2 or 3 ring heteroatoms independently selected from N, O or S, and where the phenyl or heteroaryl is optionally substituted by R5 and further substituted by 0 or 1 substituents selected from halogen, C1-C4alkyl, C1-C4alkoxy, hydroxy C1-C4alkyl, hydroxy, and cyanomethyl;
• R5 is —C(O)R8, —CH2C(O)R8, R9, —C(O)NHSO2C1-C4alkyl, —SO2NHC(O)C1-C4alkyl, —SO2N(H)m(C1-C4alkyl)2-m, —SO2C1-C4alkyl, cyano, halogen, hydroxyC1-C4alkyl and 5 member heteroaryl having 1-4 ring nitrogen atoms and 0 or 1 ring sulfur or oxygen atoms;
• m is 0, 1, or 2;
• W is O or C(R6)2;
• R6 is independently selected at each occurrence from the group consisting of hydrogen, hydroxy, amino, mono- and di-C1-C4alkylamino, C1-C4alkyl, hydroxyC1-C4alkyl, cyanoC1-C4alkyl or C1-C4alkoxy;
• or
• C(R6)2, taken in combination, form a spirocyclic carbocycle having 3 to 6 ring atoms;
• R7 is hydroxy, C1-C4alkoxy, amino or mono- and di-C1-C4alkylamino;
• R8 is hydroxy, C1-C4alkoxy, amino or a 5 to 7 member saturated heterocycle having 1, 2, or 3 ring heteroatoms independently selected from N, O or S;
• or
• R8 is mono- and di-C1-C4alkylamino which is unsubstituted or substituted with halogen, hydroxy or C1-C4alkyl;
• and
• R9 is a 5 membered heteroaryl having 1 to 4 ring nitrogen atoms and 0 or 1 ring oxygen or sulfur atoms, which heterocycle is optionally substituted by 0 to 2 C1-C4alkyl groups.