SDP-containing heterobifunctional agents

Patent metadata

Field	Value
Publication number	US-9145361-B2
Application number	US-201214006129-A
Country	US
Kind code	B2
Filing date	Mar 22, 2012
Priority date	Mar 25, 2011
Publication date	Sep 29, 2015
Grant date	Sep 29, 2015

Abstract

The present disclosure is directed to a reactive ester agent for conjugating a click-reactive group to a carrier molecule or solid support. The reactive ester agent has the general formula IA, wherein the variables R 1 , R 2 , R 3 , R a and L are described throughout the application.

First claim

The invention claimed is:

1. A compound of Formula IA or a salt thereof:

wherein
L is a linker,
R 1 is a halogen,
R 2 is a halogen,
R 3 comprises a water solubilizing group, and
R a is a click-reactive group selected from the group consisting of an alkyne reactive moiety, an azide reactive moiety, a diene, a dienophile, an epoxide or an aziridine compound.

2. The compound of claim 1 , where the click-reactivity of R a is copper-catalyzed.

3. The compound of claim 1 , where the click-reactivity of R a is not copper-catalyzed.

4. The compound of claim 1 , wherein L is a covalent bond, -alkyl-, -substituted alkyl-, -alkenyl-, -substituted alkenyl-, -heterocyclyl-, -substituted heterocyclyl-, -aryl-, -substituted aryl-, -heteroaryl-, -substituted heteroaryl-, -cycloalkyl-, -substituted cycloalkyl-, -oxy-, -alkoxy-, -substituted alkoxy-, -alkoxyalkyl-, poly(alkoxyalkyl)-, PEG, -thio-, -amino-, or -substituted amino-.

5. The compound of claim 1 , wherein R 1 and R 2 are chloro.

6. The compound of claim 1 , wherein R 3 is —COO − , —SO 3 − , substituted azenyl, PEG, phosphate, or bisphosphonate.

7. The compound of claim 5 , wherein R 3 is —SO 3 − .

8. The compound of claim 1 , wherein the compound of Formula IA is a salt.

9. The compound of claim 8 , wherein the salt comprises a potassium ion, a sodium ion, or a triethylammonium ion.

10. The compound of claim 1 , wherein R a is an alkyne reactive moiety or an azide reactive moiety.

11. The compound of claim 7 , wherein R a is an alkyne reactive moiety or an azide reactive moiety.

12. The compound of claim 11 , where the compound has the formula comprising:

13. The compound of claim 11 , where the compound has the formula comprising:

14. The compound of claim 11 , where the compound has the formula comprising:

wherein A is a substituted or unsubstituted cyclooctyne ring that may contain a heteroatom and/or be fused to one or more 5- or 6-membered aromatic or heteroaromatic rings.

15. The compound of claim 12 , wherein the compound is

16. The compound of claim 13 , wherein the compound is

17. The compound of claim 14 , wherein the compound is selected from the group consisting of:

18. A method of click-labeling a carrier molecule or solid support, said method comprising:
contacting said carrier molecule or solid support comprising a nucleophilic group X and having the formula R b —X with a compound of Formula IA or a salt thereof:

wherein
L is a linker,
R 1 is a halogen,
R 2 is a halogen,
R 3 comprises a water solubilizing group, and
R a is a click-reactive group selected from the group consisting of an alkyne reactive moiety, an azide reactive moiety, a diene, a dienophile, an epoxide or an aziridine compound;
and
forming a compound of Formula I or a salt thereof:

wherein
L is the linker,
R a is the click-reactive group, and
R b is the carrier molecule or solid support comprising the nucleophilic group X.

19. A click-labeled carrier molecule prepared by the method of claim 18 .

Assignees

• Gee Kyle
• Chen Aimei
• Kang Hee Chol
• Life Technologies Corp

Inventors

• Gee Kyle
• Chen Aimei
• Kang Hee Chol

Classifications

• C07D223/26

  having a double bond between positions 10 and 11 · CPC title

• C07D225/08 Primary

  condensed with two six-membered rings · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07D225/02

  not condensed with other rings · CPC title

• C07D223/08

  Oxygen atoms · CPC title