Cyclooctenes for bioorthogonol reactions

• US 10,179,775 B2
• Filed: 08/11/2015
• Issued: 01/15/2019
• Est. Priority Date: 08/11/2014
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Hilderbrand, Scott A., Varga, Balazs R., Weissleder, Ralph
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US15/502,806
• Publication Number:
  US 20170233365A1
• Time in Patent Office: 1,253 Days
• CPC Class Codes: C07C 2601/18 with a ring being at least seven-membered
• CPC Class Codes: C07C 43/196 containing hydroxy or O-metal groups
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 263/52 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 321/12 Eight-membered rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

This disclosure relates to trans-cyclooctene compounds and methods of using the same in bioorthogonal labeling experiments.

Claims

1. A compound of Formula I:

2. The compound of claim 1, wherein the compound of Formula I is a compound of Formula IA:

3. The compound of claim 1, wherein R² is selected from H and C_1-6alkyl.

4. The compound of claim 1, wherein R² is an amine-reactive crosslinking group selected from the group consisting of an isothiocyanate, an isocyanate, an acyl azide, an NHS ester, a sulfonyl chloride, an aldehyde, a glyoxal, an epoxide, an oxirane, a carbonate, an aryl halide, an imidoester, a carbodiimide, an anhydride, a hydrazine, a hydrazide, a hydroxyl amine, and a fluorophenyl ester.

5. The compound of claim 4, wherein R² is an NHS ester which is an NHS carbamate.

6. The compound of claim 5, wherein the NHS carbamate is N,N′

-disuccinimidyl carbonate.

7. The compound of claim 1, wherein n is 1.

8. The compound of claim 1, wherein the compound of Formula I is selected from the group consisting of:

9. A compound of Formula II:

10. The compound of claim 9, wherein R³ is H.

11. The compound of claim 9, wherein R⁵ is a C_1-6alkyl.

12. The compound of claim 9, wherein R⁵ is an amine-reactive crosslinking group selected from the group consisting of an isothiocyanate, an isocyanate, an acyl azide, an NHS ester, a sulfonyl chloride, an aldehyde, a glyoxal, an epoxide, an oxirane, a carbonate, an aryl halide, an imidoester, a carbodiimide, an anhydride, a hydrazine, a hydrazide, a hydroxyl amine, and a fluorophenyl ester.

13. The compound of claim 12, wherein R⁵ is an NHS ester which is an NHS carbamate.

14. The compound of claim 13, wherein the NHS carbamate is N,N′

-disuccinimidyl carbonate.

15. The compound of claim 9, wherein n is 3.

16. The compound of claim 9, wherein the compound of Formula II is selected from the group consisting of:

17. A compound of Formula III:

18. The compound of claim 17, wherein R⁷ is a H.

19. The compound of claim 17, wherein R⁷ is an amine-reactive crosslinking group selected from the group consisting of an isothiocyanate, an isocyanate, an acyl azide, an NHS ester, a sulfonyl chloride, an aldehyde, a glyoxal, an epoxide, an oxirane, a carbonate, an aryl halide, an imidoester, a carbodiimide, an anhydride, a hydrazine, a hydrazide, a hydroxyl amine, and a fluorophenyl ester.

20. The compound of claim 19, wherein R⁷ is an NHS ester which is an NHS carbamate.

21. The compound of claim 20, wherein the NHS carbamate is N,N′

-disuccinimidyl carbonate.

22. The compound of claim 17, wherein n is 1.

23. The compound of claim 17, wherein m is 2.

24. The compound of claim 17, wherein the compound of Formula III is selected from the group consisting of: