Granted Patent B2

US 12,290,571 · App. 16/639,499 · Granted May 6, 2025

Inventors: Tracy Matray (Snohomish, WA); Hesham Sherif (Redmond, WA)

Assignee: Sony Group Corporation

A61K47/6889A61K47/545A61K47/59A61K47/6801

Abstract

Claims (51)

1. A compound having the following structure (IA):

or a stereoisomer, pharmaceutically acceptable salt or tautomer thereof, wherein:

M is, at each occurrence, independently a biologically active moiety selected from an non-steroidal anti-inflammatory drug (NSAID), a kinase inhibitor, an anthracycline, an epidermal growth factor receptor (EGFR) inhibitor, an alkylating agent, and an anti-cancer drug, or a fluorescent dye, provided at least one occurrence of M is not a fluorescent dye;

L 1 and L 2 are, at each occurrence, independently an alkylene, heteroalkylene, or heteroatomic linker, wherein the heteroatomic linker is one or more heteroatoms;

L 4 is, at each occurrence, independently an alkylene or heteroalkylene, or absent;

L 5 is, at each occurrence, independently an alkylene or absent;

L 6 is, at each occurrence, independently a linker comprising an amide bond, an ester bond, a disulfide bond, a double bond, a triple bond, an ether bond, a ketone, a diol, a cyano, a nitro or combinations thereof;

L 7 and L 8 are, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;

R 1 is, at each occurrence, independently H, alkyl or alkoxy;

R 2 is —OP(═R a )(R b )R c ;

R 3 is, at each occurrence, independently OH, —OP(═R a )(R b )R c , Q or has the following structure:

R a is O or S;

R b is OH, SH, O − , S − , OR d or SR d ;

R c is OH, SH, O − , S − , OR d , OL′, SR d , alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;

R d is a counter ion;

R 4 is, at each occurrence, independently OH, SH, O − , S − , OR d or SR d ;

R 5 is, at each occurrence, independently oxo, thioxo or absent;

Q is, at each occurrence, independently a moiety having one of the following structures:

wherein:

each X is independently a halogen; and

EWG is an electron withdrawing group;

L′ is, at each occurrence, independently a linker comprising a covalent bond to Q, a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, a linker comprising a covalent bond to a nucleoside or a linker comprising a covalent bond to a further compound of structure (IA), wherein the targeting moiety is an antibody or cell surface receptor antagonist;

L 2 ′ is, at each occurrence, independently a direct bond, an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;

L 3 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene linker, or absent;

n is, at each occurrence, independently an integer of one or greater;

m is, at each occurrence, independently an integer of one or greater;

p is, at each occurrence, independently an integer of one to ten; and

q is, at each occurrence, independently an integer of zero or greater;

wherein R 2 or at least one of occurrence of R 3 has the following structure:

2. The compound of claim 1 , wherein at least one occurrence of R 3 has the following structure:

wherein:

L 2 ′ is a direct bond.

3. The compound of claim 1 , wherein L 3 is a heteroalkylene linker.

4. The compound of claim 1 , wherein m is, at each occurrence, independently an integer from 1 to 25.

5. The compound of claim 1 , wherein n is, at each occurrence, independently an integer from 1 to 10.

6. The compound of claim 1 , wherein R 3 is each independently OH or —OP(═R a )(R b )R c .

7. The compound of claim 1 , wherein R 3 is Q.

8. The compound of claim 1 , wherein R 3 is each independently —OP(═R a )(R b )R c .

9. The compound of claim 8 , wherein R c is OL′.

10. The compound of claim 9 , wherein L′ is a targeting moiety or a linker to a targeting moiety.

11. The compound of claim 1 , wherein R 2 or R 3 has one of the following structures:

12. The compound of claim 1 , wherein M is, at each occurrence, independently an anti-cancer drug, and the targeting moiety is an antibody specific for a tumor cell antigen.

13. The compound of claim 1 , wherein the compound has one of the following structures:

wherein N′ or I′ is M,

wherein N′ has the following structure:

wherein I′ has the following structure:

wherein dT is a deoxythymidine (dT) group and has the following structure:

wherein: R is H.

14. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

15. A method of treating a disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , wherein each M is independently a biologically active moiety effective for treating the disease.

16. The compound of claim 1 , wherein M, at each occurrence, independently has one of the following structures:

Assignments (3)

Continuity (2)

References Cited (400)

Cited By (2)

US 12,461,106 US 12,629,425