Azetidine-substituted fluorescent compounds

Patent metadata

Field	Value
Publication number	US-10161932-B2
Application number	US-201816000614-A
Country	US
Kind code	B2
Filing date	Jun 5, 2018
Priority date	Apr 1, 2014
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The presently-disclosed subject matter includes azetidine-substituted fluorescent compounds, where the compounds may be used as probes, dyes, tags, and the like. The presently-disclosed subject matter also includes kits comprising the same as well as methods for using the same to detect a target substance.

First claim

What is claimed is:

1. A composition, comprising a compound and a binding element, wherein the compounds is of the formula:

wherein:
each R is independently selected from halogen, H, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , SO 3 H, and alkyl, alkyl being optionally substituted with halogen, ═O, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), NH 2 , NHR, NR 2 , NO 2 , CHO, COO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , and/or SO 3 H;
Q is selected from CR 2 , NR, O, SiR (2) , and Se;
W is selected from C and N;
X is selected from a lone pair of electrons, H, alkyl, aryl, halogen, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , and SO 3 H, X being optionally substituted with halogen, ═O, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), NH 2 , NHR, NR 2 , NO 2 , CHO, COO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), C(O)NR 2 , PO 3 H 2 , and/or SO 3 H;
Y is selected from H, CR (2) , C(O)NR 2 , NR, O, and S; and
Z is selected from H, halogen, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , SO 3 H, aryl, and alkyl, alkyl and aryl being optionally substituted with halogen, ═O, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), NH 2 , NHR, NR 2 , NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , and SO 3 H, or wherein Z and Y, taken together with the atoms to which they are bonded, can form a substituted or unsubstituted 5-7 membered ring.

2. The composition of claim 1 , wherein the binding element binds the compound reversibly or irreversibly.

3. The composition of claim 1 , wherein the binding element is bound to the compound.

4. The composition of claim 1 , wherein the binding element is selective for a target substance.

5. The composition of claim 1 , wherein the binding element comprises a polypeptide, an amino acid, a polynucleotide, a nucleotide, or a nucleoside.

6. The composition of claim 1 , wherein the binding element comprises an antibody, an antibody fragment, or an antigen.

7. The composition of claim 1 , wherein the binding element comprises a cell or a virus.

8. The composition of claim 1 , wherein the binding element comprises a hormone.

9. The composition of claim 1 , wherein the binding element comprises a synthetic polymer or a polymeric microparticle.

10. The composition of claim 1 , wherein the binding element comprises a polysaccharide or a lipid.

11. The composition of claim 1 , wherein the binding element comprises an enzymatic substrate.

12. The composition of claim 1 , wherein X partially or wholly comprises a linker joining the compound to the binding element.

13. The composition of claim 1 , wherein X partially or wholly comprises a binding element.

14. The composition of claim 1 , wherein amine is independently selected from NH 2 , NH(alkyl), NH(aryl), N(alkyl) 2 , and N(aryl) 2 .

15. The composition of claim 1 , wherein Y and Z, taken together with the atoms to which they are bonded, form the 5-7 membered ring substituted with one or more substituents selected from halogen, CN, ═O, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), NH 2 , NHR, NR 2 , NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , SO 3 H, and alkyl.

16. The composition of claim 3 , wherein Y and Z, taken together with the atoms to which they are bonded, form the 5-7 membered ring substituted with an unsubstituted or substituted azetidine group.

17. The composition of claim 1 , wherein the compound is according to the following formula:

wherein R′ is selected from halogen, H, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , SO 3 H, and alkyl, alkyl being optionally substituted with halogen, ═O, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), —NH 2 , NHR, NR 2 , NO 2 , CHO, COO, COOH, COO(alkyl), COO(aryl), PO 3 H 2 , and/or SO 3 H.

18. The composition of claim 1 , wherein the compound is according to the following formula:

wherein R′ is selected from an azetidine group that is unsubstituted or substituted with one or more of halogen, H, CN, OH, O(alkyl), O(aryl), SH, S(alkyl), S(aryl), amine, NO 2 , CHO, COOH, C(O)NR 2 , COO(alkyl), COO(aryl), PO 3 H 2 , SO 3 H, and alkyl.

19. The composition of claim 1 , wherein the compound is according to the following formula:

20. The composition of claim 1 , wherein the compound is according to the following formula:

21. The composition of claim 1 , wherein the compound is according to the following formula:

22. The composition of claim 1 , wherein the compound is according to the following formula:

23. The composition of claim 1 , wherein the compound is according to the following formula:

24. The composition of claim 1 , wherein the compound is according to the following formula:

25. The composition of claim 1 , wherein the compound is according to the following formula:

26. The composition of claim 1 , wherein the compound is according to the following formula:

27. The composition of claim 1 , wherein X is a substituted aryl.

28. The composition of claim 1 , wherein X is selected from:

29. The composition of claim 1 , wherein X is selected from H and a lone pair of electrons.

30. The composition of claim 1 , wherein the compound is according to a formula selected from:

31. A method for detecting a target substance, comprising: contacting a

Assignees

• Hughes Howard Med Inst

Inventors

• Lavis Luke D
• Grimm Jonathan B
• Chen Jiji
• Lionnet Timothee
• Zhang Zhengjian
• Revyakin Andrey
• Slaughter Joel

Classifications

• C09B69/008

  Dyes containing a substituent, which contains a silicium atom · CPC title

• G01N33/582

  with fluorescent label · CPC title

• C09K11/06

  containing organic luminescent materials · CPC title

• C09K2211/1044

  containing two nitrogen atoms as heteroatoms · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title