Matrix metalloproteinase inhibitors and imaging agents, and methods using same

Patent metadata

Field	Value
Publication number	US-11286251-B2
Application number	US-201716088868-A
Country	US
Kind code	B2
Filing date	Apr 7, 2017
Priority date	Apr 8, 2016
Publication date	Mar 29, 2022
Grant date	Mar 29, 2022

Abstract

The present invention provides certain compounds, or salts or solvates thereof, which can be used as matrix metalloproteinase-targeted inhibitors or imaging agents.

First claim

What is claimed is:

1. A compound selected from the group consisting of:

or a salt, solvate, stereoisomer, or tautomer thereof.

2. A compound of formula I, or a salt, solvate, stereoisomer, or tautomer thereof:

wherein:
R is —NHR 1 ;
R 1 is selected from the group consisting of:

R 2 is selected from the group consisting of:

R 3 is selected from the group consisting of

and
each occurrence of n is independently an integer ranging from 0 to 30;

wherein the compound further comprises a radioisotope, which is bound to R 3 . in its place.

3. The compound of claim 2 , wherein the radioisotope is at least one selected from the group consisting of 99m Tc, 18 F, 111 In, 64 Cu, and 68 Ga.

4. The compound of claim 3 , which is at least one selected from the group consisting of:

or a salt, solvate, stereoisomer, or tautomer thereof, wherein M is a metal.

5. A pharmaceutical composition comprising at least one compound of claim 2 and further comprising at least one pharmaceutically acceptable carrier.

6. A compound of formula II or a salt, solvate, stereoisomer, or tautomer thereof:

wherein:
R is selected from the group consisting of H, OH, alkoxy, cycloalkoxy, aroxy, heteroaroxy, SH, thioalkoxy, thiocycloalkoxy, —NH 2 , —NHR′, —NR′R′, —NH(aryl), and —NH(heteroaryl); and
each occurrence of R′ is independently selected from the group consisting of C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl.

7. The compound of claim 6 , which is selected from the group consisting of:

or a salt, solvate, stereoisomer, or tautomer thereof.

8. A pharmaceutical composition comprising at least one compound of claim 6 and further comprising at least one pharmaceutically acceptable carrier.

9. A kit comprising at least one compound of claim 2 , an applicator, and instructions to use the at least one compound to evaluate a subject's risk of developing a cardiovascular disease or disorder or to treat a matrix metalloproteinase-related disease or disorder in a subject.

10. A kit comprising at least one compound of claim 6 , an applicator, and instructions to use the at least one compound to evaluate a subject's risk of developing a cardiovascular disease or disorder or to treat a matrix metalloproteinase-related disease or disorder in a subject.

Assignees

• Univ Yale
• Us Veterans Affairs

Inventors

• Sadeghi Mehran
• Ye Yunpeng
• Kim Hye-Yeong
• Huang Henry(Yiyun)
• Toczek Jakub

Classifications

• C07D273/01

  having one nitrogen atom · CPC title

• A61K51/044

  having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins (rifampin A61K51/0459) · CPC title

• A61K51/065

  conjugates with carriers being macromolecules · CPC title

• C07D413/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K51/088

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title