Isatoic anhydride derivatives and applications thereof

Patent metadata

Field	Value
Publication number	US-9867883-B2
Application number	US-201615331196-A
Country	US
Kind code	B2
Filing date	Oct 21, 2016
Priority date	Apr 24, 2014
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

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. An isatoic anhydride derivative having 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, aikoxy, 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 isatoic anhydride derivative of claim 1 , wherein p is 1, L 2 is a linker group and R 1 is a chemically reactive group.

3. The isatoic anhydride derivative of claim 2 , wherein R 1 represents an azide, alkyne, protected thiol, a group including a disulfide moiety, alkene, arylalkene maleimide, acetal, aldehyde, ketone, ketal, hydrazone, epoxide, N-hydroxysuccinimide ester, a (sulfo)N-hydroxysuccinimide ester group, a thioester, a boronic acid, a boronic ester, or a trialkoxysilyl group.

4. The isatoic anhydride derivative of claim 1 , wherein p is 1, L 2 is a linker group and R 1 is a binding group.

5. The isatoic anhydride derivative of claim 4 , wherein R 1 represents a biotin group or a hapten.

6. The isatoic anhydride derivative of claim 1 , wherein p is 1, L 2 is a linker group and R 1 represents a detectable label.

7. The isatoic anhydride derivative 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 or 2 and L 2 represents a pendant C 1-60 organo when p is 0.

8. The isatoic anhydride derivative of claim 7 , wherein L 1 and L 2 independently represent R 5 , Ar, R 5 —Ar, Ar—R 5 , R 5 —Ar—R 5 , —(CH 2 )n-, —(R 5 O)m-(CH 2 )n-, —(CH 2 )n-, —(R 5 O)m-R 5 , —(CH 2 )n-(OR 5 )m-R 5 , with or without heteroatoms along the main chain, and —(CH 2 )n-(OR 5 )m-XR 5 , and —(CH 2 )n 1 -(OR 5 )m 1 -HA-(CH 2 )n 2 -(OR 5 )m 2 -R 5 , wherein R 5 represents a C 1-8 aliphatic; Ar represents a di-radical aryl group; n, n 1 and n 2 independently represent integers of 1 to 30; m, m 1 , and m 2 independently represent integers of 0 to 30; HA represents —CO—, —C(O)X—, —XC(O)—, —X—, —S—, —S(O)—, —XS(O) 2 —, —S(O) 2 X—; and X represents O, S, NH, or NR 5 provided that if X is —NH—, the secondary amine does not substantially react with the anhydride of the isatoic anhydride derivative.

Assignees

• Univ North Carolina Charlotte

Inventors

• Ogle Craig A
• Fowler Anthony J

Classifications

• C12N2310/16

  Aptamers · CPC title

• A61K47/59

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• C12N2310/351

  Conjugate · 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

• A61K47/545 Primary

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