Compositions, methods, and systems for the synthesis and use of imaging agents

Patent metadata

Field	Value
Publication number	US-9713651-B2
Application number	US-201314420810-A
Country	US
Kind code	B2
Filing date	Aug 9, 2013
Priority date	Aug 10, 2012
Publication date	Jul 25, 2017
Grant date	Jul 25, 2017

Abstract

The present invention provides compounds with imaging moieties for imaging a subject. The present invention also relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, a composition or plurality of imaging agents is enriched in 18 F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs.

First claim

What is claimed:

1. A compound comprising the structure:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from the group consisting of alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, and an imaging moiety;
R 2 is hydrogen;
R 3 is selected from the group consisting of alkyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, and alkoxyalkyl optionally substituted halo;
J is selected from the group consisting of S, O, CH 2 O, and a bond;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, alkyl optionally substituted, and an imaging moiety;
n is 0, 1, 2, or 3;
W is heteroaryl, or aryl;
each R 6 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, heteroalkyl optionally substituted, alkoxy optionally substituted, aryloxy optionally substituted, heteroaryloxy optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, halo, haloalkyl, —N(R 7 ) 2 , —NO 2 , —OH, —C(═O)R 8 , —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)N(R 7 ) 2 , —N(R 7 )C(═O)R 8 , —CN, —OR 8 , and an imaging moiety;
m is 0, 1, 2, 3, 4, 5, 6, or 7;
each R 7 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, and aryl optionally substituted;
each R 8 is independently selected from the group consisting of hydrogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkoxyalkyl optionally substituted, aryl optionally substituted, heteroaryl optionally substituted, and haloalkyl;
wherein the optional substituent may be an imaging moiety, and provided that at least one imaging moiety is present in the compound and is 18 F; and
provided that when W is aryl, R 3 is selected from the group consisting of unsubstituted alkyl or alkyl optionally substituted with a moiety other than a halogen, heteroalkyl optionally substituted, alkoxy optionally substituted, and alkoxyalkyl optionally substituted.

2. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof, wherein I m is an imaging moiety.

3. A pharmaceutical composition comprising a compound or a salt thereof of claim 1 , and optionally a pharmaceutically acceptable excipient.

4. A sterile aqueous solution comprising a compound or a salt thereof of claim 1 .

5. A method of imaging, comprising administering to a subject a compound or salt thereof of claim 1 , and acquiring at least one image of a portion of the subject.

6. A method of detecting, imaging or monitoring myocardial perfusion, comprising administering to a subject a compound or salt thereof of claim 1 , and scanning the subject using diagnostic imaging.

7. A diagnostic kit comprising one or more vials containing a precursor to a compound or a salt thereof of claim 1 ; and optionally other components.

8. A sterile aqueous solution comprising a compound or a salt thereof of claim 6 .

9. A method of imaging, comprising administering to a subject a compound or salt thereof of claim 2 , and acquiring at least one image of a portion of the subject.

10. A method of detecting, imaging or monitoring myocardial perfusion, comprising administering to a subject a compound or salt thereof of claim 2 , and scanning the subject using diagnostic imaging.

11. The compound of claim 1 , wherein J is O or S.

12. The compound of claim 1 , wherein W is aryl.

13. The compound of claim 1 , wherein W is naphthyl.

14. The compound of claim 1 , wherein W is phenyl.

15. The compound of claim 1 , wherein R 3 is unsubstituted alkyl.

16. The compound of claim 1 , wherein R 3 is methyl.

17. The compound of claim 1 , wherein W is aryl and R 3 is unsubstituted alkyl.

18. The compound of claim 1 , wherein W is phenyl and R 3 is unsubstituted alkyl.

Assignees

• Lantheus Medical Imaging Inc

Inventors

• Cesati Richard R
• Radeke Heike S
• Pandey Suresh K
• Purohit Ajay
• Robinson Simon P

Classifications

• A61K51/0421

  having six-membered rings with one oxygen as the only ring hetero atom · CPC title

• C07D237/04

  having less than three double bonds between ring members or between ring members and non-ring members · CPC title

• C07D401/12

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

• C07F7/0812

  comprising a heterocyclic ring · CPC title

• B01J19/24

  Stationary reactors without moving elements inside (B01J19/08, B01J19/26 take precedence; with stationary particles B01J8/02) · CPC title