Phospholipid drug conjugate, method of its production and application

Inventors

ЧЖАН, Фуяо
ЦАЙ, Шэнюнь
ЧЭНЬ, Сяньцзе

Assignees

ШАНХАЙ БЕСТ-ЛИНК БАЙОСАЙЕНС, ЭлЭлСи

Dates

Publication Date: 20260506
Application Date: 20240927
Priority Date: 20230927

Claims (20)

1. A phospholipid drug conjugate represented by formula (I),
formula (I)
or a stereoisomer of said phospholipid drug conjugate, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,
Where:
X 0 - O or S;
X 1 - O, S or NR 1a ;
X 2 - O, S or NR 2a ;
L 1 , L 2 are absent or represent a linking block;
M 0 - OR 0a , SR 0b , NR 0c R 0d or T 0 -(LD) n ;
K 1 - P 1 or ; Y 1 - branching center; P 1 - pharmacokinetic regulatory block; M 1 - T 1 -(LD) n ;
Y 2 - branching center;
M 2 is absent or T 2 -(LD) n ;
at least one of M 0 , M 1 and M 2 contains an LD fragment;
Q 2a - T 2a -R 1 or absent; Q 2b - T 2b -R 2 or absent; at least one of Q 2a and Q 2b is present;
T 0 , T 1 , T 2 - each is independently selected from the missing or extended parts;
T 2a , T 2b are absent or represent a linking block;
L is L3 - Ls , where L3 is a medium-responsive linking unit selected from enzyme-responsive linkers, pH-responsive linkers, light-responsive linkers, and redox-responsive linkers; Ls is present or absent, and if present, is a self-disintegrating linking moiety;
D is a fragment of a biologically active molecule; if there are several D in the conjugate, D may be the same or different;
R 1a and R 2a are each independently selected from: hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 3 -C 10 alkene, C 3 -C 10 alkyne, C 3 -C 8 cycloalkyl, C 2 -C 8 heterocycloalkyl, C 6 -C 10 aryl, C 5 -C 10 heteroaryl, or an amino protecting group;
R 0a - each independently selected from: hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 3 -C 10 alkene, C 3 -C 10 alkyne, C 3 -C 8 cycloalkyl, C 2 -C 8 heterocycloalkyl, C 6 -C 10 aryl, C 5 -C 10 heteroaryl or a hydroxo protecting group;