# US 10,308,606 B2 · PSMA-targeted NIR dyes and their uses

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- Number: US 10,308,606 B2
- Document ID: US10308606B2
- Status: Granted
- Kind: B2
- Application number: 15/699,124
- Filed: 2017-09-08
- Published: 2018-04-12
- Granted: 2019-06-04
- Earliest claimed: 2016-09-09
- Assignees: On Target Laboratories, LLC
- Applicants: On Target Laboratories, LLC
- Inventors: Sumith A. Kularatne; Pravin Gagare
- Web page: https://patentgrep.com/patent/US10308606B2

## CPC

- C07D 209/20: substituted additionally by nitrogen atoms, e.g. tryptophane
- A61K 49/00: Preparations for testing in vivo
- A61K 49/0032: {Methine dyes, e.g. cyanine dyes}
- A61K 49/0052: {Small organic molecules (oligomers, polymers, dendrimers A61K49/0054)}
- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61K 49/0056: {Peptides, proteins, polyamino acids}
- C09B 23/0066: {the polymethine chain being part of a carbocyclic ring,(e.g. benzene, naphtalene, cyclohexene, cyclobutenene-quadratic acid)}
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 33/57555: of the prostate
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- C07D 209/24: with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- 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)
- C09B: ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES {, e.g. PIGMENTS}; MORDANTS; LAKES (fermentation or enzyme using processes to synthesise a desired chemical compound C12P)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for a method for synthesizing a compound of the formula:

## Claims

### Claim 1

A method for synthesizing a compound of the formula:
wherein n is 0, 1, 2, 3, or 4;
further wherein R3, R4, and R5 are independently selected from the group consisting of H+, Na+, K+, and NH4+; R6, R7, R8, and R9 are independently selected from the group consisting of H+, Na+, K+, and NH4+; and R10H+;
comprising the steps of:
(a) reacting a compound of formula I:
with a compound of formula:
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N-Diisopropylethylamine under argon and
(b) reacting the resulting compound with sodium carbonate and a dye compound of the formula

### Claim 2 (depends on 1)

The method of claim 1, wherein the polar organic solvent is selected from the group consisting of dimethyl sulfoxide, dimethylformamide, and water.

### Claim 3

A method for synthesizing an isotopic form of a compound of the formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H2, H3, C13 and C14;
further wherein n is 0, 1, 2, 3, or 4;
further wherein R3, R4, and R5 are independently selected from the group consisting of H+, Na+, K+, and NH4+; R6, R7, R8, and R9 are independently selected from the group consisting of H+, Na+,K+, and NH4+;and R10H+;
comprising the steps of:
(a) reacting an isotopic form of a compound of formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H2, H3, C13 and C14,
with an isotopic form of a compound of formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H2, H3, C13 and C14,
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N-Diisopropylethylamine under argon to provide an isotopic form of a compound that comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H2, H3, C13 and C14,
(b) reacting the isotopic form of the compound obtained in step (a) with sodium carbonate and an isotopic form of a dye compound of the formula:
wherein said isotopic form comprises one or more carbon and/or hydrogen isotopes selected from the group consisting of H2, H3, C13 and C14.

### Claim 4

A method for synthesizing a compound of the formula:
wherein n is 0, 1, 2, 3, or 4
(a) reacting a compound of formula
with a compound of formula:
in the presence of a polar organic solvent, 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate and N,N -Diisopropylethylamine under argon
(b) reacting the resulting compound thereof with sodium carbonate and a dye compound of the formula: