Ligands for imaging cardiac innervation

Patent metadata

Field	Value
Publication number	US-12324845-B2
Application number	US-202217587454-A
Country	US
Kind code	B2
Filing date	Jan 28, 2022
Priority date	Dec 26, 2006
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

A method of imaging, the method comprising administering, to a subject, a compound of Structure Alpha, of the formula:

or a pharmaceutically acceptable salt thereof, wherein:
n is 0;
R, R 1 , and R 3 are independently selected from the group consisting of H, OR 4 , F, Cl, Br, I, CF 3 , alkyl (C 1 -C 4 ), aryl, heteroaryl, C(═O)R 4 , CO 2 R 4 , N(R 4 ) 2 , CN, C(═NR 4 )OR 5 , NR 4 C(═NR 5 )NHR 6 , C(═NR 4 )NHR 5 , C(═O)NHR 4 , NR 4 C(═O)NR 5 , NR 4 NR 5 , SO 2 OR 4 , and imaging moiety Im;
R 2 is absent;
R 4 , R 5 , and R 6 are independently selected from the group consisting of H, alkyl, aryl and heteroaryl substituents; wherein the alkyl, aryl, or heteroaryl may be substituted with imaging moiety Im, wherein optionally any two of R 4 , R 5 , and R 6 form a cyclic structure selected from the group consisting of —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 , —CH═CH—, —X═CH—, and —X—CH═CH—, wherein X is selected from the group consisting of O, NH, and NR 7 , and wherein R 7 is selected from the group consisting of alkyl, aryl, and heteroaryl substituents;
W, X, Y and Z are independently selected from the group consisting of H, OR 4 , N(R 4 ) 2 , F, Cl, Br, I, CF 3 , imaging moiety Im, aryl, and heteroaryl;
A is O or absent; and
imaging moiety Im is 18 F, 76 Br, 124 I, 131 I, 99m Tc, 153 Gd, or 111 In;
and acquiring at least one image of the subject.

First claim

What is claimed is:

1. A method of imaging, the method comprising administering, to a subject, a compound of Structure Alpha, of the formula:

or a pharmaceutically acceptable salt thereof, wherein:
n is 0;
R, R 1 , and R 3 are independently selected from the group consisting of H, OR 4 , F, Cl, Br, I, CF 3 , alkyl (C 1 -C 4 ), aryl, heteroaryl, C(═O)R 4 , CO 2 R 4 , N(R 4 ) 2 , CN, C(═NR 4 )OR 5 , NR 4 C(═NR 5 )NHR 6 , C(═NR 4 )NHR 5 , C(═O)NHR 4 , NR 4 C(═O)NR 5 , NR 4 NR 5 , SO 2 OR 4 , and imaging moiety Im;
R 2 is absent;
R 4 , R 5 , and R 6 are independently selected from the group consisting of H, alkyl, aryl and heteroaryl substituents; wherein the alkyl, aryl, or heteroaryl may be substituted with imaging moiety Im, wherein optionally any two of R 4 , R 5 , and R 6 form a cyclic structure selected from the group consisting of —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 , —CH═CH—, —X═CH—, and —X—CH═CH—, wherein X is selected from the group consisting of O, NH, and NR 7 , and wherein R 7 is selected from the group consisting of alkyl, aryl, and heteroaryl substituents;
W, X, Y and Z are independently selected from the group consisting of H, OR 4 , N(R 4 ) 2 , F, Cl, Br, I, CF 3 , imaging moiety Im, aryl, and heteroaryl;
A is O or absent; and
selected from the group consisting of 18 F, 76 Br, 124 I, 131 I, 99m Tc, 153 Gd, and 111 In;
and acquiring at least one image of the subject.

2. The method of claim 1 , wherein the method utilizes PET imaging techniques to acquire the at least one image.

3. The method of claim 1 , wherein the method utilizes SPECT imaging techniques to acquire the at least one image.

4. The method of claim 1 , wherein:
A is absent;
X, W, R and R 3 are hydrogen;
R 1 is NHC(═NH)NH 2 ;
Y is H, F, Cl, or Br; and
Z is OR 4 , wherein R 4 is alkyl substituted with 18 F.

5. The method of claim 1 , wherein any two of R 4 , R 5 , and R 6 form a cyclic structure selected from the group consisting of —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 , —CH═CH—, —X═CH—, and —X—CH═CH—,
wherein X is selected from the group consisting of O, NH, and NR 7 , and
wherein R 7 is selected from the group consisting of alkyl, aryl and heteroaryl substituents.

6. The method of claim 1 , wherein A is absent.

7. The method of claim 1 , wherein X and R 3 are hydrogen.

8. The method of claim 1 , wherein the imaging moiety Im is 18 F.

9. The method of claim 1 , wherein the compound of Structure Alpha has the structure:

or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein the compound of Structure Alpha has the structure:

or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the compound of Structure Alpha has the structure:

or a pharmaceutically acceptable salt thereof.

Assignees

• Lantheus Medical Imaging Inc

Inventors

• Purohit Ajay
• Harris Thomas D
• Radeke Heike S
• Robinson Simon P
• Yu Ming
• Casebier David S
• Azure Michael T

Classifications

• A61K51/0459

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title

• A61K51/0453

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• C07C279/08

  being further substituted by singly-bound oxygen atoms · CPC title

• C07C279/06

  being further substituted by halogen atoms, or by nitro or nitroso groups · CPC title

• C07C217/70

  linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring · CPC title