Super lewis acidic borate esters as 18F-labeled PET probes

Patent metadata

Field	Value
Publication number	US-9409927-B2
Application number	US-201414762544-A
Country	US
Kind code	B2
Filing date	Jan 24, 2014
Priority date	Jan 24, 2013
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

Compounds having a 1-bora-1-fluoro-2,6,7-trioxabicyclo[2.2.2]octane moiety wherein the fluorine is 18 F are described. Also described are reagents for radiolabeling a molecule having Formula I. Method for radiolabeling molecules with the disclosed reagents are also descried, as are radiolabeled molecules prepared thereby.

First claim

What is claimed is:

1. A reagent for radiolabeling a molecule having Formula I:

wherein F is 18 F, L is a bond or a linker of from 1 to 20 atoms in length and Y is a reactive moiety capable of forming a bond with another molecule.

2. The reagent of claim 1 , wherein L is a linker from 1-10 atoms in length.

3. The reagent of claim 1 , wherein L is a substituted or unsubstituted, branched or unbranched, alkyl, alkenyl, or alkynyl group, ether, ester, polyether, polyester, polyalkylene, polyamine, heteroatom substituted alkyl, alkenyl, or alkynyl group, cycloalkyl group, cycloalkenyl group, heterocycloalkyl group, or heterocycloalkenyl group, any of which is optionally substituted with acetyl, alkyl, amino, amido, alkoxyl, alkylhydroxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, carbonyl, halogen, hydroxyl, thiol, cyano, or nitro.

4. The reagent of claim 1 , wherein L is a C 1 -C 6 branched or straight-chain alkyl, or a C 2 -C 6 branched or straight-chain alkyl, wherein one or more of the carbon atoms are substituted with oxygen or an amino group, any of which is optionally substituted with acetyl, alkyl, amino, amido, alkoxyl, alkylhydroxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, carbonyl, halogen, hydroxyl, thiol, cyano, or nitro.

5. The reagent of claim 1 , wherein L is X 1 —(CH 2 ) m —X 2 , wherein m is from 1 to 10, and X 1 and X 2 are, independent of one another, CH 2 , C(O), C(O)O, C(O)N, NH, or O.

6. The reagent of claim 1 , wherein L is —C(O)CH 2 CH 2 C(O)—.

7. The reagent of claim 1 , wherein Y is a protected or unprotected alanine, allosoleucine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isolelucine, leucine, lysine, phenylalanine, methionine, proline, pyroglutamic acid, serine, threonine, tyrosine, tryptophan, or valine.

8. The reagent of claim 1 , wherein Y is an aldehyde, acyl azide, acyl nitrile, ester, succinimidyl ester, sulfosuccinimidyl ester, anhydride, mixed anhydride, carboxylic acid, epoxide, imine, isocyanate, isothiocyanate, sulfonyl chloride, halogen, maleimide, hydrazine, amine, amide, alcohol, carboxylate, or thiol.

9. The reagent of claim 1 , wherein Y has a formula chosen from:

where n is 1, 2, 3, 4, or 5; and
each R 1 , independent of the others, is halogen, hydroxyl, cyano, nitro, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkoxyl, substituted or unsubstituted aryloxyl, or substituted or unsubstituted carboxyl.

10. The reagent of claim 1 , wherein the reagent has a formula chosen from:

11. The reagent of claim 1 , wherein the reagent has a formula chosen from:

Assignees

• Univ South Florida
• H Lee Moffitt Cancer Ct & Res

Inventors

• Mclaughlin Mark Lee
• Tian Haibin

Classifications

• C07B2200/05

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

• C07K7/56

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• C07B59/004

  Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium · CPC title

• C07B59/008

  Peptides; Proteins · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title