Steroids and protein-conjugates thereof

Patent metadata

Field	Value
Publication number	US-12377159-B2
Application number	US-202318361275-A
Country	US
Kind code	B2
Filing date	Jul 28, 2023
Priority date	Nov 8, 2016
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

Described herein are protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.

First claim

What is claimed is:

1. A compound of Formula (A):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 and R 2 together form

wherein R 4 is linear or branched alkyl, aryl, arylalkyl, or an N-containing heterocycloalkyl,
wherein the alkyl, aryl, arylalkyl, and N-containing heterocycloalkyl are, independently in each instance, optionally substituted with —NR c R d ,
wherein R c and R d are, independently in each instance, —H, alkyl, or optionally substituted aryl;

R 3 is —NR a R b ,
wherein R a and R b are, independently in each instance, —H, alkyl, or optionally substituted aryl;

R 5 is, independently in each instance, —OH, halo, alkyl, or arylalkyl; and
n is an integer from 0-19.

2. The compound of claim 1 , wherein the compound of Formula (A) is a compound of Formula (A 1 ):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 , R 2 , and R 3 are as defined above; and
R 5A and R 5B are, independently in each instance, —H or halo.

3. The compound of claim 2 , wherein:
R 1 and R 2 together form

wherein R 4 is linear or branched alkyl, aryl, or arylalkyl,
wherein the alkyl, aryl, and arylalkyl are, independently in each instance, optionally substituted with —NR c R d ,
wherein R c and R d are, independently in each instance, —H, alkyl, or optionally substituted aryl.

4. The compound of claim 1 , wherein R a is H and R b is H or alkyl.

5. The compound of claim 1 , wherein the compound of Formula (A) is a compound of Formula (A 4 ):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 3 is —NR a R b ;
R 4 is linear or branched alkyl; and
R a and R b are, independently in each instance, —H or alkyl.

6. The compound of claim 5 , wherein R 4 is C 1-4 linear or branched alkyl.

7. The compound of claim 5 , wherein R 3 is —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 .

8. The compound of claim 1 , wherein the compound of Formula (A) is a compound of Formula (A 6 ):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 3 is —NR a R b ;
R 4 is linear or branched alkyl; and
R a and R b are, independently in each instance, —H or alkyl.

9. The compound of claim 1 , wherein the compound of Formula (A) is a compound of Formula 1110, 1120, 1130 or 1140:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 3 and R 4 are as defined above.

10. The compound of claim 9 wherein R 4 is n-propyl.

11. The compound of claim 10 according to formula 1120.

12. The compound of claim 9 wherein R 4 is H 2 NCH 2 CH 2 — or

13. The compound of claim 1 wherein R 4 is linear or branched alkyl, aryl, or arylalkyl.

14. The compound of claim 13 wherein R 3 is —NH 2 , —N(H)CH 3 , or —N(CH 3 ) 2 .

15. The compound of claim 13 wherein R 4 is n-propyl.

16. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

18. The compound of claim 1 , of the formula

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

19. The compound of claim 1 , of the formula

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

20. The compound of claim 1 , of the formula

or a pharmaceutically acceptable salt or solvate.

21. The compound of claim 1 , according to Formula (A 2 )

wherein n is an integer from 0 to 4.

22. The compound of claim 1 , according to Formula (A 3 ):

wherein n is an integer from 1-4.

23. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

Assignees

• Regeneron Pharma

Inventors

• Han Amy
• Murphy Andrew J
• Olson William

Classifications

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K47/6803 Primary

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• C07J71/0031 Primary

  at positions 16, 17 · CPC title

• C07J41/005

  the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives · CPC title

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title