One-step, fast, 18F-19F isotopic exchange radiolabeling of difluoro-dioxaborinins and use of such compounds in treatment
Inventors
Ting, Richard • Aras, Omer • An, Feifei • Chen, Nandi
Assignees
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Publication Number
US-12378261-B2
Publication Date
2025-08-05
Expiration Date
Abstract
A compound according to Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, wherein X1 and X2 are each independently 18F or 19F; R1 and R2 are each independently alkyl, amine, perfluoroalkyl, alkenyl, alkynyl, aryl, or aralkenyl; and R3 is H, halo, alkyl, alkyl ester, alkenyl, alkynyl, aryl, or aralkenyl; or wherein: R1 and R3 or R2 and R3 join to form a 6-membered cycloalkyl or heterocyclyl; or R1 and R3, R2 and R3, or R1, R2, and R3 join to form a substituted or unsubstituted polycyclic ring, wherein the polycyclic ring comprises fused cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings.
Core Innovation
The invention relates to difluoro-dioxaborinin compounds defined by Formula (I), including compounds where X1 and X2 are each independently 18F or 19F. The substituent definitions include R1, R2, and R3, and selected pairs or triplets of these substituents can join to form a substituted or unsubstituted polycyclic ring framework.
Within the Formula (I) framework, the disclosed compound set includes tetracycline-BF2, glycylcycline-BF2, emodin-BF2, doxorubicin-BF2, and daunorubicin-BF2, as well as related difluoro-dioxaborinin members where fluorine substituents are present as 18F and/or 19F. The document further includes difluoro-dioxaborinin radiolabeling and isotopic exchange and discusses solvolysis half-life over a reported range, supported by analytical characterization and solvolysis data.
The disclosed compounds are presented as cancer imaging and cancer treatment-related agents, including PET and fluorescence (PET/FL) imaging. The document also describes detection after administration using positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission, together with pharmaceutical compositions and kit formulations that include precursor forms for imaging and related use.
Claims Coverage
The independent claim covers difluoro-dioxaborinin compounds of Formula (I) with the specific BF2-conjugated tetracycline- and anthracycline-family members, where X1 and X2 are each independently 18F or 19F. The claim scope is additionally tied to ring-formation via R substituent joining and includes pharmaceutically acceptable salts and/or solvates.
Difluoro-dioxaborinin compounds of Formula (I) with X1 and X2 being 18F or 19F
A compound according to Formula (I) (or a pharmaceutically acceptable salt and/or solvate thereof) wherein X1 and X2 are each independently 18F or 19F.
Substituted or unsubstituted polycyclic ring formation from R substituents
R1 and R3, R2 and R3, or R1, R2, and R3 join to form a substituted or unsubstituted polycyclic ring.
Specific BF2-conjugated members: tetracycline-BF2, glycylcycline-BF2, emodin-BF2, doxorubicin-BF2, or daunorubicin-BF2
The compound of Formula (I) (or a pharmaceutically acceptable salt and/or solvate thereof) is tetracycline-BF2, glycylcycline-BF2, emodin-BF2, doxorubicin-BF2, or daunorubicin-BF2.
Overall, the claim coverage centers on Formula (I) difluoro-dioxaborinin compounds with independently 18F/19F fluorine substituents, polycyclic ring formation from R1/R2/R3 joining, and specific BF2-conjugated tetracycline and anthracycline-family members (tetracycline-BF2, glycylcycline-BF2, emodin-BF2, doxorubicin-BF2, or daunorubicin-BF2).
Stated Advantages
Rapid room-temperature isotopic exchange.
High specific activity.
Low starting dose.
Stability, with no more than about 50% degradation in 24 h.
Documented Applications
Cancer imaging and cancer treatment-related agents using PET and fluorescence (PET/FL), including post-administration detection modalities based on positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission.
In vivo imaging context including sentinel lymph node imaging.
Cancer treatment in a subject by administering a therapeutically effective amount of the compound.
Pharmaceutical composition and kit formulations including precursor forms for imaging and related use.
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