US 12,290,567 B2
Asialoglycoprotein Receptor mediated delivery of therapeutically active conjugates
Kumar Rajappan, San Diego, CA (US); Padmanabh Chivukula, San Diego, CA (US); Kiyoshi Tachikawa, San Diego, CA (US); Steven Tanis, Carlsbad, CA (US); and Priya Karmali, San Diego, CA (US)
Assigned to Arcturus Therapeutics, Inc., San Diego, CA (US)
Filed by Arcturus Therapeutics, Inc., San Diego, CA (US)
Filed on Sep. 3, 2020, as Appl. No. 17/011,880.
Claims priority of provisional application 62/895,417, filed on Sep. 3, 2019.
Prior Publication US 2021/0060168 A1, Mar. 4, 2021
Int. Cl. A61K 47/54 (2017.01); C07H 15/04 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/549 (2017.08) [C07H 15/04 (2013.01); C12N 15/113 (2013.01); C12N 2310/3515 (2013.01)] 19 Claims
 
1. A compound of Formula IA

OG Complex Work Unit Chemistry
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—N—(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—N—(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

OG Complex Work Unit Chemistry
 wherein X4 is optionally substituted;
RN is H, methyl, or mono-, di-, or trifluoromethyl;
Q is akyalkylamino, —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 1-10; j is 1-10; and R3 is hydrogen or an alkyl;
L4 is absent, —C(O)O—, —C(O)NH—, —O—P(O)2—O—, C1-C10 alkyl-O—P(O)2—O—, C3-C10 alkenyl-O—P(O)2—O—, —O—P(O)(S)—O—, C1-C10 alkyl-O—P(O)(S)—O—, C3-C10 alkenyl-O—P(O)(S)—O—, —O—P(O)(BH3)—O—, a C1-C10 alkyl-O—P(O)(BH3)—O—, a C3-C10 alkenyl-O—P(O)(BH3)—O—, —C(O)NH—C1-C10alkyl-O—P(O)2—O—, —C(O)NH—C3-C10alkenyl-O—P(O)2—O—, —C(O)O—C1-C10alkyl-O—P(O)2—O—, —C(O)O—C3-C10alkenyl-O—P(O)2—O—, —C(O)NH—C1-C10alkyl-O—P(O)(S)—O—, —C(O)NH—C3-C10alkenyl-O—P(O)(S)—O—, —C(O)O—C1-C10alkyl-O—P(O)(S)—O—, —C(O)O—C3-C10alkenyl-O—P(O)(S)—O—, —C(O)—NH—C1-C10alkyl-O—P(O)(BH3)—O—, —C(O)—NH—C3-C10alkenyl-O—P(O)(BH3)—O—, —C(O)O—C1-C10alkyl-O—P(O)(BH3)—O— or —C(O)O—C3-C10alkenyl-O—P(O)(BH3)—O—; and
R1 is a biologically active molecule.