Asialoglycoprotein receptor mediated delivery of therapeutically active conjugates

A compound of Formula IA

• or a pharmaceutically acceptable salt or solvate thereof, wherein
• X1, X2 and X3 are each independently selected from the group consisting of C1-C10 alkyl, —(CH2)m—O—(CH2)n— and —(CH2)m—NRN—(CH2)n—, wherein n is 1-36 and m is 1-30;
• Y1, Y2 and Y3 are each independently selected from the group consisting of —NHC(O)—, —C(O)NH—, —OC(O)—, —C(O)O—, —SC(O)—, —C(O)S— and P(Z)(OH)O2, wherein Z is O or S;
• L1, L2 and L3 are each independently selected from the group consisting of a C1-C10 alkyl, —(CH2)e—O—(CH2)f—, —(CH2)e—S—(CH2)f—, —(CH2)e—S(O)2—(CH2)f—, —(CH2)e—NRN—(CH2)f— and —(CH2—CH2—O)k(CH2)2—, wherein e is 1-10, f is 1-16 and k is 1-20;
• G1, G2 and G3 are each independently selected from the group consisting of a monosaccharide, a monosaccharide derivative, a vitamin, a polyol, a polysialic acid and a polysialic acid derivative;
• X4 is selected from the group consisting of
• (a) —(CH2)g—O—(CH2)h— or —(CH2)g—NRN—(CH2)h—, wherein g is 1-30 and h is 1-36,
• (b) an amino acid, and
• (c) —NHC(O)R2, wherein R2 is C1-C10 alkyl, a carbocycle, a heterocyclyl, a heteroaryl, a C1-C10 alkyl-carbocycle, a C1-C10 alkyl-heterocyclyl or a C1-C10 alkyl-heteroaryl, and wherein R2 is optionally substituted;
• RN is H, methyl, or mono-, di-, or trifluoromethyl;
• Q is absent, alkylamino, —C(O)—(CH2)i—, —(CH2)i—O—(CH2)j—, —(CH2)i—NR3—(CH2)j—, —(CH2)i—S—S—(CH2)j—, —(CH2)i—S—(CH2)j—, —(CH2)i—S(O)2—(CH2)j—, —(CH2)i—NHC(O)—(CH2)j—, —(CH2)i—C(O)NH—(CH2)j—, —(CH2)i—SC(O)—(CH2)j—, or —(CH2)i—C(O)S—(CH2)j—, wherein i is 1-30;
• j is 1-36;
• and R3 is hydrogen or an alkyl;
• L4 is absent, —C(O)O—, —C(O)NH—, a phosphate, C1-C10 alkyl-phosphate, C3-C10 alkenyl-phosphate, a phosphorothioate, alkyl-phosphorothioate, C3-C10 alkenyl-phosphorothioate, a boranophospate, a C1-C10 alkyl-boranophospate, a C3-C10 alkenyl-boranophospate, —C(O)NH—C1-C10alkyl-phosphate, —C(O)NH—C3-C10alkenyl-phosphate, —C(O)O—C1-C10alkyl-phosphate, —C(O)O—C3-C10alkenyl-phosphate, —C(O)NH—C1-C10 alkyl-phosphorothioate, —C(O)NH—C3-C10 alkenyl-phosphorothioate, —C(O)O—C1-C10alkyl-phosphorothioate, —C(O)O—C3-C10alkenyl-phosphorothioate, —C(O)—NH—C1-C10alkyl-boranophospate, —C(O)—NH—C3-C10alkenyl-boranophospate, —C(O)O—C1-C10alkyl-boranophospate or —C(O)O—C3-C10alkenyl-boranophospate;
• and
• R1 is a biologically active molecule.