One-step, fast, 18F-19F isotopic exchange radiolabeling of difluoro-dioxaborinins and use of such compounds in treatment

Patent metadata

Field	Value
Publication number	US-12378261-B2
Application number	US-201917057284-A
Country	US
Kind code	B2
Filing date	May 23, 2019
Priority date	May 23, 2018
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

A compound according to Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, wherein X 1 and X 2 are each independently 18 F or 19 F; R 1 and R 2 are each independently alkyl, amine, perfluoroalkyl, alkenyl, alkynyl, aryl, or aralkenyl; and R 3 is H, halo, alkyl, alkyl ester, alkenyl, alkynyl, aryl, or aralkenyl; or wherein: R 1 and R 3 or R 2 and R 3 join to form a 6-membered cycloalkyl or heterocyclyl; or R 1 and R 3 , R 2 and R 3 , or R 1 , R 2 , and R 3 join to form a substituted or unsubstituted polycyclic ring, wherein the polycyclic ring comprises fused cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings.

First claim

What is claimed is:

1. A compound according to Formula (I)

or a pharmaceutically acceptable salt and/or solvate thereof, wherein
X 1 and X 2 are each independently 18 F or 19 F; and
R 1 and R 3 , R 2 and R 3 , or R 1 , R 2 , and R 3 join to form a substituted or unsubstituted polycyclic ring;

wherein the compound of Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof is tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 .

2. The compound of claim 1 , wherein the compound of Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof is tetracycline-BF 2 or glycylcycline-BF 2 .

3. The compound of claim 2 , wherein each fluorine atom of tetracycline-BF 2 or glycylcycline-BF 2 is independently 18 F or 19 F.

4. The compound of claim 1 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, is emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 .

5. The compound of claim 4 , wherein each fluorine atom of emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 18 F or 19 F.

6. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers.

7. A method comprising administering a compound of claim 1 to a subject suffering from a cancer.

8. The method of claim 7 , wherein the method comprises administering an effective amount of the compound for imaging the cancer.

9. The method of claim 7 , further comprising, subsequent to the administering, detecting one or more of positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission.

10. The method of claim 7 , wherein the administration comprises intravenous administration.

11. A method for inhibiting the proliferation of one or more cancer cells, the method comprising contacting the one or more cancer cells with a compound of claim 1 .

12. A method for treating cancer in a subject comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1 .

13. The pharmaceutical composition of claim 6 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

14. The method of claim 7 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

15. The method of claim 8 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

16. The method of claim 9 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

17. The method of claim 11 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

18. The method of claim 12 , wherein at least one fluorine atom of tetracycline-BF 2 , glycylcycline-BF 2 , emodin-BF 2 , doxorubicin-BF 2 , or daunorubicin-BF 2 is independently 19 F.

Assignees

• Univ Cornell
• Memorial Sloan Kettering Cancer Center

Inventors

• Ting Richard
• Aras Omer
• An Feifei
• Chen nandi

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title