Azetidine-substituted fluorescent compounds

Patent metadata

Field	Value
Publication number	US-9933417-B2
Application number	US-201515301270-A
Country	US
Kind code	B2
Filing date	Apr 1, 2015
Priority date	Apr 1, 2014
Publication date	Apr 3, 2018
Grant date	Apr 3, 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 compound 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 compound of claim 1 , wherein amine is independently selected from NH 2 , NH(alkyl), NH(aryl), N(alkyl) 2 , and N(aryl) 2 .

3. The compound 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.

4. The compound 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.

5. The compound of claim 1 , 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.

6. The compound of claim 1 , 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.

7. The compound of claim 1 , according to the following formula:

8. The compound of claim 1 , according to the following formula:

9. The compound of claim 1 , according to the following formula:

10. The compound of claim 1 , according to the following formula:

11. The compound of claim 1 , according to the following formula:

12. The compound of claim 1 , according to the following formula:

13. The compound of claim 1 , according to the following formula:

14. The compound of claim 1 , according to the following formula:

15. The compound of claim 1 , wherein X is a substituted aryl.

16. The compound of claim 1 , wherein X is selected from:

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

18. A compound according to a formula selected from:

19. A method for detecting a target substance, comprising:
contacting a sample with a compound 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, S, 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), 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; and
detecting an emission light from the compound, the emission light indicating the presence of the target substance.

20. The method of c

Assignees

• Hughes Howard Med Inst

Inventors

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

Classifications

• C09B11/28

  Pyronines {; Xanthon, thioxanthon, selenoxanthan, telluroxanthon dyes} · CPC title

• C09B57/02

  Coumarine dyes · CPC title

• C07D473/18

  one oxygen and one nitrogen atom, e.g. guanine · CPC title

• C07D405/04

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

• C07D493/10

  Spiro-condensed systems · CPC title