Granted Patent B2

US 12,433,950 · App. 17/835,395 · Granted Oct 7, 2025

Inventors: Yongxin Robert Zhao (Hangzhou, CN); Qingliang Yang (Hangzhou, CN); Yuanyuan Huang (Hangzhou, CN); Hangbo Ye (Hangzhou, CN); Huihui Guo (Hangzhou, CN)

Assignee: HANGZHOU DAC BIOTECH CO., LTD.

A61K47/6803A61K47/68031A61K47/68035A61K47/6829A61K47/6831A61K47/6855A61K47/6863A61K47/6883A61K47/6889

Abstract

Claims (48)

1. A linker compound of Formula (I) or (II):

wherein

“ ” and “ ” represent a single bond, and “ ” can be an enantiomer or stereoisomer bond when linked to a single or a double bond;

represents either a single bond, or a double bond, or a triple bond;

provided that when represents a single bond, both L V1 and L V2 are not H; when represents a double bond, either L V1 or L V2 can be H, but they are not H at the same time; when represents a triple bond, L V1 is absent and L V2 can optionally be H;

L V1 and L V2 , represent H or a same or different leaving group that is optionally substituted by a thiol, and the leaving group is selected from the group consisting of a halide selected from fluoride, chloride, bromide, and iodide, methanesulfonyl (mesyl), toluenesulfonyl (tosyl), trifluoromethyl-sulfonyl (triflate), trifluoromethylsulfonate, nitrophenoxyl, N-succinimidyloxyl (NHS), phenoxyl; dinitrophenoxyl; pentafluorophenoxyl, tetrafluorophenoxyl, trifluorophenoxyl, difluorophenoxyl, monofluorophenoxyl, pentachlorophenoxyl, 1H-imidazole-1-yl, chlorophenoxyl, dichlorophenoxyl, trichlorophenoxyl, tetrachlorophenoxyl, N-(benzotriazol-yl)oxyl, 2-ethyl-5-phenylisoxazolium-3′-sulfonyl, phenyloxadiazole-sulfonyl (-sulfone-ODA), 2-ethyl-5-phenylisoxazolium-yl, phenyloxadiazol-yl (ODA), and oxadiazol-yl;

Y is a functional group that selected from the group consisting of following structures:

 disulfide;

 haloacetyl;

 acyl halide (acid halide);

 N-hydroxysuccinimide ester;

 maleimide;

 monosubstituted maleimide;

 disubstituted maleimide;

 monosubstituted succinimide;

  disubstituted succinimide; —CHO aldehyde;

 ethenesulfonyl;

 acryl (acryloyl);

 2-(tosyloxy)acetyl;

 2-(mesyloxy)acetyl;

 2-(nitrophenoxy)acetyl;

 (dinitrophenoxy)acetyl;

 2-(fluorophenoxy)-acetyl;

 2-(difluorophenoxy)-acetyl;

 2-(((trifluoromethyl)-sulfonyl)oxy)acetyl;

 ketone, or aldehyde,

 2-(pentafluorophenoxy)acetyl;

 methylsulfonephenyloxadiazole (ODA);

 acid anhydride,

 alkyloxyamino;

 azido,

 alkynyl and

 hydrazide, wherein X 1′ is F, Cl, Br, I or L V3 ; X 2 ′ is O, NH, N(Ria), or CH 2 ; R 3 and R 5 are independently H, R 1a , aromatic, heteroaromatic, or aromatic group wherein one or several H atoms are replaced independently by —R 1a , -halogen, —OR 1a , —SR 1a , —NR 1a R 2 , —NO 2 , —S(O)R 1a , —S(O) 2 R 1a , or —COOR 1a ; L V3 is a leaving group selected from the group consisting of nitrophenol; N-hydroxysuccinimide (NHS); phenol; dinitrophenol; pentafluorophenol; tetrafluorophenol; difluorophenol; monofluorophenol; pentachlorophenol; triflate; imidazole; dichlorophenol; tetrachlorophenol; 1-hydroxybenzotriazole; tosylate; mesylate; 2-ethyl-5-phenylisoxazolium-3′-sulfonate, and anhydrides formed its self, or formed with acetyl anhydride, or formyl anhydride; R 1a is selected from the group consisting of H, C 1 -C 8 alkyl; C 2 -C 8 heteroalkyl, alkylcycloalkyl, heterocycloalkyl; C 3 -C 8 aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, heteroaryl; C 2 -C 8 ester, ether, amide, amine, imine, polyamine, hydrazine, hydrazone, urea, semicarbazide, carbazide, alkoxyamine, alkoxylamine, urethane, amino acid, acyloxylamine, glycoside, or hydroxamic acid: peptide containing 1-8 amino acids, or polyethyleneoxy unit of formula (OCH 2 CH 2 ) p or (OCH 2 CH(CH 3 )) p , wherein p is an integer from 1 to about 1000, and a combination thereof;

R 1 is absent;

T is

 wherein is the site of linkage,

X 2 , X 3 , and X 5 each are NHNH;

m, m 1 , m 2 , m 3 , m 4 and m 5 are independently an integer from 1 to 10,

L 1 is alkylcarbonyl;

L 2 , and X 1 are absent.

2. The linker compound of claim 1 , wherein represents a triple bond.

3. The linker compound of claim 1 , wherein represents a triple bond, and L V2 is H.

4. The linker compound of claim 1 , wherein Y is

5. The linker compound of claim 1 , wherein represents a triple bond, L V2 is H, and Y is

6. The linker compound of claim 1 , wherein represents a single bond, and L V1 and L V2 represent Br or I.

7. The linker compound of claim 1 , wherein represents a double bond, and L V1 and L V2 represent H or Br.

8. The linker compound of claim 1 , wherein m 1 is 2.

9. The linker compound of claim 1 , wherein m 5 is 2.

Assignments (1)

Continuity (2)

References Cited (122)