US 11,993,626 B2
Functionalized N-acetylgalactosamine analogs
Wing C. Poon, Union City, CA (US); Xiaoyang Guan, Union City, CA (US); David Yu, Union City, CA (US); Ruiming Zou, Union City, CA (US); Xiaojun Li, Union City, CA (US); Michael Su, Union City, CA (US); Gang Zhao, Union City, CA (US); Gengyu Du, Union City, CA (US); Yun-Chiao Yao, Union City, CA (US); and Aldrich N. K. Lau, Palo Alto, CA (US)
Assigned to Hongene Biotech Corporation, Union City, CA (US)
Filed by Hongene Biotech Corporation, Union City, CA (US)
Filed on Dec. 13, 2022, as Appl. No. 18/065,503.
Claims priority of provisional application 63/290,010, filed on Dec. 15, 2021.
Prior Publication US 2023/0279041 A1, Sep. 7, 2023
Int. Cl. C07H 15/26 (2006.01); C07H 21/00 (2006.01)
CPC C07H 15/26 (2013.01) [C07H 21/00 (2013.01)] 31 Claims
 
1. A compound of Formula (II):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
each of R1a, R1b, R1c, R2a, R2b, R2c, R3a, R3b, and R3c is independently hydrogen, benzyl, or —C(═O)R8;
each of R4a, R4b and R4c is independently —C(═O)C1-6 alkyl or —C(═O)C1-6 haloalkyl;
R5 is a hydroxy protecting group;
R6 is hydrogen, a phosphoramidite moiety, —C(═O)CH2CH2C(═O)R6A, or —P(OR6B)NR6CR6D;
Y2 is a bond, NR7, NR7C(═O), C(═O)O, or O;
each of X1, X2 and X3 is independently —O(CH2)1-3—, —NH(CH2)1-3—, —C(═O)(CH2)1-3— or —NHC(═O)(CH2)1-3-;
each of L1a, L1b, L1c, L2a, L2b, L2c, L3a, L3b, and L3c is independently a bond, —C(═O)—, —C(═S)—, —S(═O)2—, —C(═O)NR9—, —C(═S)NR9—, —C(═O)O—, —C(═S)O—, —NR9C(═O)NR9—, —NR9C(═S)NR9—, —OP(═O)(OH)O—, —OP(═S)(OH)O—, —O—, —S—, —NR9—, optionally substituted C1-10 alkylene, optionally substituted C6-10 arylene, optionally substituted C3-10 cycloalkylene, optionally substituted 5-10 membered hetetroarylene, optionally substituted 5 to 10 membered heterocyclylene, or optionally substituted 2 to 15 membered heteroalkylene wherein one or more carbon atoms are replaced with C(═O), O, S or N, provided that at least one of L1a, L1b and L1c is not a bond, at least one of L2a, L2b and L2c is not a bond, and at least one of L3a, L3b and L3c is not a bond;
L4 is a bond, optionally substituted C1-8 alkylene or —(CH2)1-3(OCH2CH2)1-5OCH2-;
L5 is a bond, optionally substituted C1-10 alkylene, or optionally substituted 2 to 15 membered heteroalkylene wherein one or more carbon atoms are replaced with C(═O), O, S or N;
each of R7 and R9 is independently hydrogen, unsubstituted C1-6 alkyl, or substituted C1-6 alkyl;
each R8 is independently C1-6 alkyl, C1-6 haloalkyl, or optionally substituted phenyl;
R6A is —OH, —OR10 or —NR11R12;
each of R6B, R6C and R6D is independently H, C1-6 haloalkyl, or unsubstituted or substituted C1-6 alkyl;
R10 is unsubstituted or substituted C1-6 alkyl, or a hydroxy protecting group;
each of R11 and R12 is independently H, unsubstituted or substituted C1-6 alkyl, or an amino protecting group;
each of m and n is independently 1, 2, 3, 4, 5 or 6;
k is 0 or 1;
x is 0, 1, 2, 3, 4, 5 or 6; and
each RN is independently halo, cyano, hydroxy, amino, unsubstituted C1-6 alkyl, substituted C1-C6 alkyl, C1-C6 haloalkyl, hydroxy(C1-C6 alkyl), amino(C1-C6 alkyl), (C1-C6 alkyl)amino, C1-C6 alkoxy, C1-C6 haloalkoxy, (C1-C6 alkoxy)C1-C6 alkyl, or —O(C1-C6 alkoxy)C1-C6 alkyl, or two adjacent RN attached to the same carbon atom form oxo (═O).