# US 2021/0276971 A1 · Triazamacrocycle-derived chelator compositions for coordination of imaging and therapy metal ions and methods of using same

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- Number: US 2021/0276971 A1
- Document ID: US20210276971A1
- Status: Published application
- Kind: A1
- Application number: 17/253,307
- Filed: 2019-06-20
- Published: 2021-09-09
- Earliest claimed: 2018-06-20
- Assignees: The Research Foundation for The State University of New York
- Applicants: The Research Foundation for The State University of New York
- Inventors: Eszter Boros; Brett Vaughn
- Web page: https://patentgrep.com/patent/US20210276971A1

## CPC

- C07D 257/02: not condensed with other rings
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention provides a compound having the structure: and methods of using the compound in targeted PET imaging.

## Claims

### Claim 1

A compound having the structure:
wherein
n is 0 or 1;
Y1, Y2 and Y3 are each, independently, —H, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylaryl-OH)2, alkyl-N(alkylheteroaryl-OH)2, alkyl-N(alkyl-CO2H)2, alkyl-N (alkylaryl-OH) (alkyl-CO2H), alkyl-N(alkylheteroaryl-OH) (alkyl-CO2H), alkyl-P(O) (OH)2, alkylaryl-P(O) (OH)2 and alkylheteroaryl-P(O) (OH)2,
wherein each occurrence of R4 is, independently, —H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3 or —Si(alkyl)3;
Z1 is
wherein X1 is NH, O or S, and
Y4 is —CO2H, —CO2R5, aryl-CO2H, heteroaryl-CO2H, aryl-CO2R5 or heteroaryl-CO2R5,
wherein each occurrence of R5 is, independently, —H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3 or —Si (alkyl)3;
A is a targeting moiety; and
L is a chemical linker,
or a pharmaceutically acceptable salt of the compound.

### Claim at position 2

2-4. (canceled)

### Claim 5 (depends on 1)

The compound of claim 1, wherein the targeting moiety A is trastuzumab, bombesin, somatostatin or 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) or a derivative or fragment thereof.

### Claim at position 4

6-8. (canceled)

### Claim 9 (depends on 1)

The compound of claim 1, wherein the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alkylheteroaryl, aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.

### Claim at position 6

10-11. (canceled)

### Claim 12 (depends on 1)

The compound of claim 1 having the structure:

### Claim at position 8

13-14. (canceled)

### Claim 16 (depends on 1)

The compound of claim 1 having the structure:

### Claim at position 10

17-20. (canceled)

### Claim 21 (depends on 1)

A metal complex comprising the compound of claim 1, wherein the compound coordinates to a metal.

### Claim 22

(canceled)

### Claim 23 (depends on 21)

The metal complex of claim 21 having the structure:
or a pharmaceutically salt thereof.

### Claim 24

(canceled)

### Claim 25 (depends on 21)

A method of detecting target cells in a subject comprising administering an effective amount of the metal complex of claim 21 to the subject, and imaging the subject with a molecular imaging device to detect the metal complex in the subject.

### Claim at position 16

26-27. (canceled)

### Claim 28 (depends on 21)

A method of detecting the presence of target cells in a subject which comprises determining if an amount of the metal complex of claim 21 or a pharmaceutically acceptable salt thereof, is present in the subject at a period of time after administration of the metal complex to the subject, thereby detecting the presence of the target cells based on the amount of the metal complex determined to be present in the subject.

### Claim 29

(canceled)

### Claim 30 (depends on 1)

The compound of claim 1
where A has the structure:
wherein
R1, R2 and R3 are each, independently, —H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3 or —Si(alkyl)3.

### Claim at position 20

31-32. (canceled)

### Claim 33 (depends on 30)

The compound of claim 30, wherein R1, R2 and R3 are each H.

### Claim at position 22

34-35. (canceled)

### Claim 36 (depends on 1)

The compound of claim 1 having the structure:
wherein
Y1 is —H,
Y2 is —H,
L is alkyl-NH,
or a pharmaceutically acceptable salt of the compound.

### Claim 37 (depends on 1)

The compound of claim 1 having the structure:
wherein
Y1 is —H,
Y2 is —H,
L is alkyl-C(O)NH-alkyl-NH,
or a pharmaceutically acceptable salt of the compound.

### Claim 38 (depends on 1)

The compound of claim 1 having the structure:
wherein
Y1 is —H,
Y2 is —H,
Y3 is —H,
L is alkyl-NH,
or a pharmaceutically acceptable salt of the compound.

### Claim 39 (depends on 1)

The compound of claim 1 having the structure:
wherein
Y1 is —H,
Y2 is —H,
Y3 is —H,
L is an alkyl-C(O)NH-alkyl chemical linker,
or a pharmaceutically acceptable salt of the compound.

### Claim 40 (depends on 1)

The compound of claim 1 having the structure:
or a pharmaceutically salt thereof.

### Claim 41

(canceled)

### Claim 42 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim at position 30

43-44. (canceled)

### Claim 45 (depends on 21)

The metal complex of claim 21 having the structure:
or a pharmaceutically salt thereof.

### Claim at position 32

46-47. (canceled)

### Claim 48 (depends on 21)

A method of imaging prostate cancer cells in a subject comprising:
1) administering to the subject an effective amount of the metal complex of claim 21 or a pharmaceutically acceptable salt thereof,
wherein the compound specifically accumulates at prostate cancer cells in the subject;
3) detecting in the subject the location of the metal complex; and
4) obtaining an image of the cancer cells in the subject based on the location of the metal complex.

### Claim 49

(canceled)

### Claim 50 (depends on 21)

A method of reducing the size of a prostate tumor or of inhibiting proliferation of prostate cancer cells comprising contacting the tumor or cancer cells with the metal complex claim 21 or a pharmaceutically acceptable salt thereof, so as to thereby reducing the size of the tumor or inhibit proliferation of the cancer cells.