Isatoic anhydride derivatives and applications thereof

Patent metadata

Field	Value
Publication number	US-10179175-B2
Application number	US-201715848750-A
Country	US
Kind code	B2
Filing date	Dec 20, 2017
Priority date	Apr 24, 2014
Publication date	Jan 15, 2019
Grant date	Jan 15, 2019

Abstract

Isatoic anhydride derivatives having an N-substituent which includes a quaternary ammonium group are useful for labeling and/or functionalizing a target material and/or for coupling materials together. The isatoic anhydride derivatives of the present disclosure can be advantageously water soluble, easily prepared and purified. Isatoic anhydride derivatives useful in the present disclosure preferably have at least one chemically reactive group or at least one binding group or at least one detectable label. Anthranilate derivatives made from the isatoic anhydrides derivatives or otherwise and kits including the isatoic anhydride derivatives are also disclosed.

First claim

What is claimed is:

1. A method of modifying a material, the method comprising combining an isatoic anhydride derivative with a material to form either (i) a isatoic anhydride derivative including the material coupled through R 1 having the structure of Formula (II) or (ii) an anthranilate derivative having the material coupled through the anhydride of the isatoic anhydride derivative having the structure of Formula (III):

wherein M represents the material, Xa represents NH, NR 5 , S, or O and R′ 1 represents a group formed from the reaction or interaction of R 1 and the material M;
wherein the isatoic anhydride derivative has the following formula:

wherein V, W, Y, and Z individually represent H, N 3 , NO 2 , amino, alkylamino, dialkylamino, branched or linear alkyl, branched or linear alkenyl, branched or linear alkynyl, branched or linear alkoxy, branched or linear sulfenyl, an alkyne or azido substituted alkylamino, dialkylamino, alkyl, alkoxy, sulfenyl, formyl, acetyl, or halide; L 1 represents a linker group; R 3 and R 4 independently represent a linear or branched alkyl, an alkyl ether, or together form a cyclic heteroalkyl, or cyclic heteroaryl; Q − represents an anion; p is an integer from 0 to 2; when p is 0, L 2 represents a pendant organo group; when p greater than 0, L 2 represents a second independent linker group; R 1 represents a chemically reactive group, a binding group, or a detectable label.

2. The method of claim 1 , comprising forming the anthranilate of Formula (III) wherein M is a biological material, p is 1 and R 1 is a chemically reactive group or a binding group.

3. The method of claim 1 , comprising forming the anthranilate of Formula (III) wherein M is a biological material, p is 1 and R 1 is a detectable label.

4. The method of claim 1 , comprising forming the anthranilate of Formula (III) wherein M is a polymeric nanoparticle.

5. The method of claim 1 , further comprising coupling another material to the anthranilate of Formula (III) by coupling or binding the second material to R 1 .

6. The method of claim 1 , wherein V and Z are H and W and Y independently represents H, N 3 , NO 2 , NH 2 , NHR 5 , NR 5 R 5 , a C 1-6 alkyl, a C 1-6 alkenyl, a C 1-6 alkynyl, an alkyne or azido substituted NHR 5 , NR 5 R 5 , C 1-6 , OC 1-6 , SC 1-6 , —CHO or acetal; R 3 and R 4 independently represent a C 1-6 alkyl or together form a 5-6 membered ring heterocycle; R 5 represents C 1-8 aliphatic; Q − represents a halide anion; L 1 represents a di-radical C 1-60 organo; L 2 represents a di-radical C 1-60 organo when p is 1 and L 2 represents a pendant C 1-60 organo when p is 0.

7. The method of claim 1 , comprising forming the anthranilate of Formula (III) and wherein p is 1; R 1 is a chemically reactive group; and M represents RNA, an RNA aptamer, DNA, a DNA aptamer, a protein, a peptide, an enzyme, a peptide aptamer, an antibody, or an antibody.

8. The method of claim 7 , wherein each of V, Z, W and Y represent H.

9. The method of claim 7 , wherein L 1 represents R 5 ; and L 2 represents —(CH 2 )n-(R 5 O)m-R 5 ; R 5 represents a C 1-8 aliphatic; n represents integers of 1 to 30; and m represents integers of 0 to 30.

10. The method of claim 7 , wherein R 3 and R 4 independently represent a linear or branched C 1-8 alkyl.

11. The method of claim 7 , wherein Q- represents a halide anion.

12. The method of claim 1 , comprising forming the anthranilate of Formula (III) and wherein L 1 represents R 5 ; and L 2 represents —(CH 2 )n-(R 5 O)m-R 5 ; R 5 represents a C 1-8 aliphatic; n represents integers of 1 to 30; and m represents integers of 0 to 30; R 3 and R 4 independently represent a linear or branched C 1-8 alkyl; Q- represents a halide anion; p is 1; R 1 is a chemically reactive group; and M represents RNA, an RNA aptamer, DNA, a DNA aptamer, a protein, a peptide, an enzyme, a peptide aptamer, an antibody, or an antibody.

13. The method of claim 12 , wherein M represents a peptide.

14. The method of claim 1 , comprising forming the anthranilate of Formula (II).

15. The method of claim 14 , wherein each of V, Z, W and Y represent H.

16. The method of claim 14 , wherein L 1 represents R 5 ; and L 2 represents —(CH 2 )n-(R 5 O)m-R 5 ; R 5 represents a C 1-8 aliphatic; n represents integers of 1 to 30; and m represents integers of 0 to 30.

17. The method of claim 14 , wherein R 3 and R 4 independently represent a linear or branched C 1-8 alkyl.

18. The method of claim 14 , wherein Q- represents a halide anion.

19. The method of claim 1 , comprising forming the anthranilate of Formula (II) and wherein L 1 represents R 5 ; and L 2 represents —(CH 2 )n-(R 5 O)m-R 5 ; R 5 represents a C 1-8 aliphatic; n represents integers of 1 to 30; and m represents integers of 0 to 30; R 3 and R 4 independently represent a linear or branched C 1-8 alkyl; Q- represents a halide anion; p is 1; R 1 is a chemically reactive group; and M represents RNA, an RNA aptamer, DNA, a DNA aptamer, a protein, a peptide, an enzyme, a peptide aptamer, an antibody, or an antibody.

20. The method of claim 19 , wherein M represents a peptide.

Assignees

• Univ North Carolina Charlotte

Inventors

• Ogle Craig A
• Fowler Anthony J

Classifications

• A61K47/593

  Polyesters, e.g. PLGA or polylactide-co-glycolide · CPC title

• C12N2310/351

  Conjugate · CPC title

• A61K47/545 Primary

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• C12N2310/16

  Aptamers · CPC title

• C12N15/115

  Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers} · CPC title