Contrast agents for myocardial perfusion imaging

Patent metadata

Field	Value
Publication number	US-9718786-B2
Application number	US-201514845320-A
Country	US
Kind code	B2
Filing date	Sep 4, 2015
Priority date	Feb 13, 2004
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

First claim

What is claimed is:

1. A method for synthesizing a compound, comprising:
reacting a precursor species having the following structure,

wherein R 3 is C 1-6 alkyl substituted with a hydroxyl group, alkoxy substituted with a hydroxyl group, or alkoxyalkyl substituted with a hydroxyl group, in the presence of p-toluenesulfonyl chloride, to produce a compound having the following structure,

wherein R 4 is C 1-6 alkyl substituted with a tosyl group, alkoxy substituted with a tosyl group, or alkoxyalkyl substituted with a tosyl group.

2. The method of claim 1 , further comprising:
reacting the compound in the presence of a 18 F-containing species to produce a contrast agent comprising 18 F.

3. The method of claim 1 , wherein the precursor species has the following structure,

4. The method of claim 1 , wherein the compound has the following structure,

5. The method of claim 1 , further comprising:
reacting a species having the following structure,

wherein R 2 is C 1-6 alkyl substituted with a protected hydroxyl group, alkoxy substituted with a protected hydroxyl group, or alkoxyalkyl substituted with protected hydroxyl group, the protected hydroxyl group comprising a trialkylsilyl group, in the presence of tetraalkylammonium fluoride, to produce the precursor species.

6. The method of claim 5 , wherein the species has the following structure,

7. The method of claim 5 , further comprising:
reacting, via an etherification reaction, a heterocyclic species having the following structure,

wherein R 1 is chloro or a hydroxyl group, with a substituted phenyl species having the following structure,

wherein R 2 is C 1-6 alkyl substituted with a protected hydroxyl group, alkoxy substituted with a protected hydroxyl group, or alkoxyalkyl substituted with a protected hydroxyl group, the protected hydroxyl group comprising a trialkylsilyl group.

8. The method of claim 7 , wherein the heterocyclic species has the following structure,

9. The method of claim 7 , wherein the substituted phenyl species has the following structure,

10. A method for synthesizing a contrast agent, comprising:
reacting a compound having the following structure,

wherein R 4 is C 1-6 alkyl substituted with a tosyl group, alkoxy substituted with a tosyl group, or alkoxyalkyl substituted with a tosyl group, in the presence of a 18 F-containing species to produce a contrast agent comprising 18 F.

11. A method for synthesizing a contrast agent, comprising:
reacting a precursor compound having the structure:

in the presence of a 18 F-containing species to produce a contrast agent comprising the structure:

12. The method of claim 11 , wherein the precursor compound is formed via reaction of p-toluenesulfonyl chloride with a hydroxyl-containing compound comprising the structure:

13. The method of claim 12 , wherein the hydroxyl-containing compound is formed via reaction of tetraalkylammonium fluoride with a species comprising the structure:

14. The method of claim 13 , wherein the species is formed via reaction with a heterocyclic species comprising the structure:

with a substituted phenyl species comprising the structure:

Assignees

• Lantheus Medical Imaging Inc

Inventors

• Casebier David S
• Purohit Ajay
• Radeke Heike S

Classifications

• A61K49/10 Primary

  Organic compounds · CPC title

• C07D237/16 Primary

  Two oxygen atoms · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title