US 11,813,334 B2
Polyethylene glycol conjugate drug, and preparation method therefor and use thereof
Gaoquan Li, Chongqing (CN); Dajun Li, Chongqing (CN); Qian Zhang, Chongqing (CN); Diedie Li, Chongqing (CN); Chengzhi Gao, Chongqing (CN); Yue Liu, Chongqing (CN); Xiaoling Ding, Chongqing (CN); Yusong Wei, Chongqing (CN); Xiangwei Yang, Chongqing (CN); Yongchen Peng, Chongqing (CN); Jia Gao, Chongqing (CN); Qiang Luo, Chongqing (CN); Yanxia Heng, Chongqing (CN); Mei Liu, Chongqing (CN); Yuyang Yi, Chongqing (CN); Xiafan Zeng, Chongqing (CN); Tao Tu, Chongqing (CN); Xiao Tang, Chongqing (CN); Xi Liu, Chongqing (CN); Jianhuan Li, Chongqing (CN); Zhaojie Wang, Chongqing (CN); Bin Wang, Chongqing (CN); Jinping Wan, Chongqing (CN); Mingyang Hou, Chongqing (CN); Jiao Liu, Chongqing (CN); Huiyu Chen, Chongqing (CN); Jie Lou, Chongqing (CN); Yue Yang, Chongqing (CN); and Yuanqiang Wang, Chongqing (CN)
Assigned to CHONGQING UPGRA BIOTECHNOLOGY CO., LTD., Chongqing (CN)
Appl. No. 17/779,825
Filed by CHONGQING UPGRA BIOTECHNOLOGY CO., LTD., Chongqing (CN)
PCT Filed Mar. 11, 2020, PCT No. PCT/CN2020/078713
§ 371(c)(1), (2) Date May 25, 2022,
PCT Pub. No. WO2021/103342, PCT Pub. Date Jun. 3, 2021.
Claims priority of application No. 201911192038.2 (CN), filed on Nov. 28, 2019.
Prior Publication US 2023/0101564 A1, Mar. 30, 2023
Int. Cl. A61K 47/60 (2017.01); A61P 35/00 (2006.01); A61K 47/64 (2017.01)
CPC A61K 47/60 (2017.08) [A61K 47/641 (2017.08); A61P 35/00 (2018.01)] 23 Claims
OG exemplary drawing
 
1. A polyethylene glycol conjugated drug of formula (I) or a pharmaceutically acceptable salt thereof;

OG Complex Work Unit Chemistry
wherein Lys represents a lysine residue, PEG1 is a single-arm, four-arm or eight-arm polyethylene glycol segment, and j represents the number of arms of PEG1;
X represents carbonyl; M represents GFLG; wherein G of M is linked to an α-amino group or an ε-amino group on Lys;
Y1 is selected from:

OG Complex Work Unit Chemistry
when j is 4 or 8, there are 4 or 8 Y1s at the same time, and in this case, the Y1s are the same or different;
W1 is selected from:

OG Complex Work Unit Chemistry
when j is 4 or 8, there are 4 or 8 W1s at the same time, and in this case, the W1s are the same or different;
Q represents

OG Complex Work Unit Chemistry
each of Z0, Z1, Z2 and Z3 is independently selected from

OG Complex Work Unit Chemistry
Z0, Z1, Z2, and Z3 may be the same or different, and when there are multiple Z0s, multiple Z1s, multiple Z2s, or multiple Z3s at the same time, the Z0s are the same or different, the Z1s are the same or different, the Z2s are the same or different, or the Z3s are the same or different;
each of N1, N2 and N3 independently is G or GFLG; N1, N2 and N3 are the same or different, and when there are multiple Nis, multiple N2s or multiple N3s at the same time, the N1s are the same or different, the N2s are the same or different, or the N3s are the same or different;
AC1, AC2 and AC3 are drug molecules with anti-tumor activity; AC1, AC2 and AC3 are the same or different, and when there are multiple AC1s, multiple AC2s or multiple AC3s at the same time, the AC1s are the same or different, the AC2s are the same or different, or the AC3s are the same or different;
W2 is selected from H, N1′-AC1′, Q′,

OG Complex Work Unit Chemistry
when j is 4 or 8, there are 4 or 8 W2s at the same time, and in this case, the W2s are the same or different;
Q′ represents

OG Complex Work Unit Chemistry
each of Z0′, Z1′ and Z2′ is independently selected from:

OG Complex Work Unit Chemistry
Z0′, Z1′ and Z2′ are the same or different, and when there are multiple Z0's, multiple Z1's or multiple Z2's at the same time, the Z0's are the same or different, the Z1's are the same or different, or the Z2's are the same or different;
each of N1′ and N2′ independently is G or GFLG; N1′ and N2′ are the same or different, and when there are multiple N1's or multiple N2's at the same time, the N1's are the same or different or the N2's are the same or different;
AC1′ and AC2′ are drug molecules with anti-tumor activity; AC1′ and AC2′ are the same or different, and when there are multiple AC1's or multiple AC2's at the same time, the AC1's are the same or different or the AC2's are the same or different;
U represents PEG2 or

OG Complex Work Unit Chemistry
wherein PEG2 represents a single-arm polyethylene glycol segment, which is linked to Y1 or Y2 through an amide bond;
Y2 represents

OG Complex Work Unit Chemistry
W3 represents N1″-AC1″, wherein N1″ is GFLG and AC1″ is a a drug molecule with anti-tumor activity).