US 11,793,881 B2
Polyethylene glycol conjugate medicament, preparation method therefor and use thereof
Gaoquan Li, Chongqing (CN); Dajun Li, Chongqing (CN); Qian Zhang, Chongqing (CN); Yusong Wei, Chongqing (CN); Yongchen Peng, Chongqing (CN); Xiangwei Yang, Chongqing (CN); Xiafan Zeng, Chongqing (CN); Gang Mei, Chongqing (CN); Diedie Li, Chongqing (CN); Chengzhi Gao, Chongqing (CN); Xiaoling Ding, Chongqing (CN); Yue Liu, Chongqing (CN); Jia Gao, Chongqing (CN); Yuyang Yi, Chongqing (CN); Yanxia Heng, Chongqing (CN); Xi Liu, Chongqing (CN); Tao Tu, Chongqing (CN); Kai Wang, Chongqing (CN); Liwei Liu, Chongqing (CN); Mei Liu, Chongqing (CN); Qiang Luo, Chongqing (CN); Xiao Tang, Chongqing (CN); Jie Lou, Chongqing (CN); Huiyu Chen, Chongqing (CN); Yue Yang, Chongqing (CN); and Yuanqiang Wang, Chongqing (CN)
Assigned to CHONGQING UPGRA BIOTECHNOLOGY CO., LTD., Chongqing (CN)
Appl. No. 17/779,649
Filed by CHONGQING UPGRA BIOTECHNOLOGY CO., LTD., Chongqing (CN)
PCT Filed Nov. 18, 2020, PCT No. PCT/CN2020/129705
§ 371(c)(1), (2) Date May 25, 2022,
PCT Pub. No. WO2021/104120, PCT Pub. Date Jun. 3, 2021.
Claims priority of application No. 201911190064 (CN), filed on Nov. 28, 2019; application No. 202010737415 (CN), filed on Jul. 28, 2020; and application No. 202010738638 (CN), filed on Jul. 28, 2020.
Prior Publication US 2023/0088403 A1, Mar. 23, 2023
Int. Cl. A61K 47/60 (2017.01); A61P 35/00 (2006.01); A61K 45/06 (2006.01)
CPC A61K 47/60 (2017.08) [A61K 45/06 (2013.01); A61P 35/00 (2018.01)] 22 Claims
 
1. A polyethylene glycol conjugated drug of formula (I) or a pharmaceutically acceptable salt thereof,

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wherein:
M is —C(═O)—C1-6 alkylene-C(═O)—, —C(═O)—, —NH—C1-6alkylene-NH—, —C(═O)—C1-6 alkylene-NH—,

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 or PEGm; wherein, PEGm is a single-arm or multi-arm polyethylene glycol segment, and its number-average molecular weight is 5k-40k;
A1, A1′ each independently are

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A2 independently is a direct bond or

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L1 independently is a direct bond or —C(═O)—C1-6 alkylene-C(═O)—;
W1, W1′, W2 each independently are Q1,

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Z4, Z3, Z2, Z1, Z0 each independently are

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Q is —N-AC;
Q1 is —N1-AC1;
Q2 is —N2-AC2;
N, N1, N2 each independently are GFLG, G,

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AC, AC1, AC2 each independently are drug molecules;
n1, n2 each independently are 0, 1, 2, 3, 4, 5 or 6;
Y, Y′ each independently are a direct bond, GLFG, —C(═O)—C1-6 alkylene-C(═O)—,

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X, X′ each independently are

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PEG is a single-arm polyethylene glycol segment, and its number-average molecular weight independently is 5k-40k;
j1 is 1, 2, 3, 4, 5 or 6;
j2, j3 each independently are 0 or 1.