Derivatives of 1,2-dihydro-7-hydroxyquinolines containing fused rings

• US 7,169,922 B2
• Filed: 11/13/2003
• Issued: 01/30/2007
• Est. Priority Date: 08/04/2000
• Status: Expired due to Term

• Current Assignee: Molecular Probes Incorporated (Thermo Fisher Scientific Incorporated)
• Original Assignee: Invitrogen Corp. (Thermo Fisher Scientific Incorporated)
• Inventors: Liu, Jixiang, Diwu, Zhenjun, Gee, Kyle
• Primary Examiner(s): POWERS, FIONA
• Application Number:
  US10/713,670
• Publication Number:
  US 20040147747A1
• Time in Patent Office: 1,174 Days
• Field of Search: 544/99, 546/28, 546/36, 546/41, 546/48, 546/61, 546/62, 546/70, 546/80, 546/89
• US Class Current: 544/99
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/044 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 491/14 Ortho-condensed systems
• CPC Class Codes: C07D 491/147 the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/14 Ortho-condensed systems
• CPC Class Codes: C07D 495/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 498/14 Ortho-condensed systems
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 2563/107 fluorescence
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10T 436/141111 Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/145555 Hetero-N

Abstract

The present invention describes novel dyes, including coumarins, rhodamines, and rhodols that incorporate additional fused aromatic rings. The dyes of the invention absorb at a longer wavelength than structurally similar dyes that do not possess the fused aromatic rings. Many of the dyes of the invention are useful fluorescent dyes. The invention includes chemically reactive dyes, dye-conjugates, and the use of such dyes in staining samples and detecting ligands or other analytes.

Claims

1. A compound of the formula

2. The compound according to claim 1, wherein one of X and E is O, or S, and the other is absent.

3. The compound according to claim 2, wherein said compound is of the formula

4. The compound according to claim 2, wherein said compound is of the formula

5. The compound according to claim 3, wherein X is S.

6. The compound according to claim 1, wherein

R¹ is hydrogen or sulfonic acid;

R³ and R⁴ are each methyl;

R⁶ and R⁷ are each hydrogen or methyl; and

Z is OH.

7. The compound according to claim 1, wherein Y is H or —

(CO)—

H or NO.

8. The compound according to claim 1, wherein said L is independently a single covalent bond or a covalent linkage having 1–

20 nonhydrogen atoms selected from the group consisting of C, N, O, P, and S.

9. The compound according to claim 1, wherein said R_X is independently selected from the group consisting of an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl nitrile, an aldehyde, an alkyl halide, an amine, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a phosphoramidite, a reactive platinum complex, a sulfonyl halide, and a thiol group.

10. The compound according to claim 1, wherein said S_C is independently selected from the group consisting of an amino acid, a peptide, a protein, a tyramine, a carbohydrate, a metal chelating moiety, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid, a hapten, a psoralen, a drug, a hormone, a lipid, a lipid assembly, a polymer, a polymeric microparticle, a biological cell, and a virus.

11. A compound of the formula

12. The compound according to claim 11, wherein said one of X and E is O or S.

13. The compound according to claim 12, wherein

R⁶ and R⁷ are hydrogen;

R³ and R⁴ are each methyl;

R¹ is hydrogen or sulfonic acid;

one of R¹⁵ and R¹⁶ is -L-R_x or -L-S_C, and the other is hydrogen, C₁–

C₆ alkyl, C₁–

C₆ perfluoroalkyl;

or cyano;

wherein L is a single covalent bond, or L is a covalent linkage having 1–

20 nonhydrogen atoms selected from the group consisting of C, N, O, P, and S, and

wherein R_X, is independently selected from the group consisting of an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl nitrile, an aldehyde, an alkyl halide, an amine, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a phosphoramidite, a reactive platinum complex, a sulfonyl halide, and a thiol group; and

wherein S_C is independently selected from the group consisting of an amino acid, a peptide, a protein, a tyramine, a carbohydrate, a metal chelating moiety, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid, a hapten, a psoralen, a drug, a hormone, a lipid, a lipid assembly, a polymer, a polymeric microparticle, a biological cell, and a virus.

14. The compound according to claim 11, wherein one of said R¹⁵ or R¹⁶ is an aromatic or heteroaromatic ring system having 1–

2 fused rings that is optionally substituted one or more times by C₁–

C₆ alkyl, C₁–

C₆ perfluoroalkyl, cyano, halogen, carboxylic acid, sulfonic acid, or halomethyl.

15. A compound of the formula:

16. The compound according to claim 15, wherein said Q is N.

17. The compound according to claim 15, wherein said J is O and said Q is CR²⁸.

18. The compound according to claim 17, wherein one of said R⁵, R²¹, R³⁰, R³¹, R³², R³³, and R³⁴ is -L-R_x or -L-S_C.

19. The compound according to claim 15, wherein

said R³ and R⁴ are each methyl;

R¹ is H or a sulfonic acid;

R⁶ is H; and

J is NR³⁷R³⁸.

20. The compound according to claim 19, wherein Q is CR²⁸ and R²⁸ is of the formula

21. A compound of the formula

22. A compound of the formula:

23. The compound according to claim 22, wherein said conjugated substance is independently selected from the group consisting of an amino acid, a peptide, a protein, a tyramine, a carbohydrate, a metal chelating moiety, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid, a hapten, a psoralen, a drug, a hormone, a lipid, a lipid assembly, a polymer, a polymeric microparticle, a biological cell, and a virus.

24. The compound according to claim 23, wherein said conjugated substance is a metal chelating moiety wherein said metal chelating moiety is optionally substituted by a reactive group.

25. The compound according to claim 24, wherein said metal chelating moiety is BAPTA.

26. The compound according to claim 25, wherein said R²⁸ is said BAPTA.

27. The compound according to claim 26, wherein said reactive group is selected from the group consisting of a carboxylic acid, a succinimidyl ester of a carboxylic acid, a maleimide, a cadaverine, a benzophenone, an aryl azide and a diazirine.

28. The compound according to claim 26, wherein said compound is according to formula

29. The compound according to claim 27, wherein said compound is according to formula