Compounds useful for in vivo imaging of protein oxidation and/or cancer treatment
AssigneeWake Forest University Health Sciences
InventorsCristina M. Furdui, Leslie B. Poole, S. Bruce King
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Abstract
Provided herein are compounds of Formula I, Formula II Formula III which are useful in labeling tissues in a subject (e.g., PET imaging of a subject), for treatment of cancer, and/or for preparing a medicament. Also provided are compounds containing a group that is reactive with sulfenylated proteins for treatment of cancer and/or for preparing a medicament. Methods of synthesis of the compounds and precursor compounds are also provided.
Claims18
A method of synthesizing a compound of Formula I:
- wherein:
- F is fluoro;
- x is an integer of from 1 to 10;
- L1 is a linker;
- and
- R1 is a group that is reactive with sulfenylated proteins, comprising:
- A) reacting a compound of formula A:
- N3—(CH2)x+1—Z, wherein Z is a leaving group, and x is as defined above, with fluorine, to form a compound:
- N3—(CH2)x+1—F;
- providing an alkyne-containing compound of formula B:
- and then
- reacting the compound N3—(CH2)x+1—F with the alkyne-containing compound of formula B, said reacting carried out by a copper-catalyzed Click reaction, or
- B) reacting a compound of formula A:
- N3—(CH2)x+1—Z, wherein Z is a leaving group, and x is as defined above, with an alkyne-containing compound of formula B:
- said reacting carried out by a copper-catalyzed Click reaction, to form a compound C:
- and then
- adding L1-R1 to the compound to form a compound D (e.g., through amide bond formation of activated carboxylic acids):
- and then
- reacting the compound D with fluorine to displace Z with the fluorine, to thereby synthesize said compound of Formula I.
A method of labeling tissues in a subject, comprising:
- administering a compound of Formula I:
- wherein:
- F is fluoro;
- x is an integer of from 1 to 10;
- L1 is a linker;
- and
- R1 is a group that is reactive with sulfenylated proteins,
- to said subject, and then
- performing a PET scan on the subject, wherein the PET scan detects the presence or absence of binding of said compound to said tissues, the presence of binding indicating the presence of sulfenylated proteins in said tissues.
A method for determining whether a cancerous tissue has an increased likelihood of responding to radiation treatment, comprising:
- administering a compound of Formula I:
- wherein:
- F is fluoro;
- x is an integer of from 1 to 10;
- L1 is a linker;
- and
- R1 is a group that is reactive with sulfenylated proteins,
- to said subject, and then
- performing a PET scan on the subject, wherein the PET scan detects the presence or absence of binding of said compound to said cancerous tissue, the presence of binding indicating an increased likelihood of response of said cancerous tissue to radiation treatment.
A method of treatment for a cancer in a subject in need thereof, comprising administering to the subject a treatment-effective amount of a compound:
- L1-R1, or L1-R1-L2-R2,
- wherein:
- L1 and L2 are each independently present or absent, and when present is independently a C1-C10 alkyl, a ketone, an amide, an ester, a carbamate, a urea, an ether, a carbonate, or a combination of two or more thereof;
- R1 is a group that is reactive with sulfenylated proteins;
- and
- R2 is a cellular directing group,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.