WO1995019976A1 - Derives chemoluminescents heterocycliques - Google Patents
Derives chemoluminescents heterocycliques Download PDFInfo
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- WO1995019976A1 WO1995019976A1 PCT/BE1995/000007 BE9500007W WO9519976A1 WO 1995019976 A1 WO1995019976 A1 WO 1995019976A1 BE 9500007 W BE9500007 W BE 9500007W WO 9519976 A1 WO9519976 A1 WO 9519976A1
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- WO
- WIPO (PCT)
- Prior art keywords
- group
- chemoluminescent
- derivatives
- formula
- optionally substituted
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
Definitions
- the present invention relates to heterocyclic chemoluminescent derivatives of acridinium, substituted acridinium derivatives, phenanthridinium, substituted phenantridinium derivatives, quinolenium, substituted quinolenium derivatives, isoquinolenium and substituted isoquinolenium derivatives as well as a conjugate comprising one of these derivatives, linked to a specific biological component.
- Another aspect of the invention relates to the diagnostic and / or assay kit comprising this conjugate or one of these derivatives, and the use of the conjugate or of one of these chemoluminescent derivatives for the assay and / or detection of a specific biological compound.
- Chemoluminescence is a formation of light obtained by a chemical reaction.
- the general mechanism of this reaction has been described in particular by Schuster et al (Advances in Physical Organic Chemistry, 187-238 (1984)) by the following reaction:
- chemoluminescence immuno assay This chemoluminescence process is widely used in analytical chemistry and clinical biology, in particular for immunoassays (chemoluminescence immuno assay or "CLIA").
- EP - A- 273115, EP - A - 257 541 and EP - A - 263657 describe heterocyclic chemoluminescent compounds derived from acr idinium, phenantr idinium, quinolenium and isoquinolenium and their isomers, optionally conjugated to antigens, antibodies or nucleic acids for use in chemoluminescence tests.
- the chemoluminescent power of these derivatives is calculated by the emission of light generated in contact with hydrogen peroxide in an alkaline medium. Studies by F. McCapra (Accounts of Chemical Research (1976), 9, 6, p. 201-209) have established a mechanism of chemoluminescence of acridinium compounds.
- the present invention aims to obtain heterocyclic derivatives of acridinium, phenant idinium, quinoline and isoquinolenium as well as their isomers and any derivatives obtained by substitution, improved, in particular stable derivatives and / or having chemoluminescence high, in particular when the pKa value of the leaving group is high, preferably when the pKa is greater than 12.
- the present invention also aims to obtain chemoluminescent derivatives characterized by a dose-response curve allowing their use in the assay and / or diagnosis over a wide concentration range.
- a final object of the present invention is to obtain a diagnostic kit comprising said active and / or stable chemoluminescent derivative. Characteristic elements of the invention.
- the present invention relates to derivatives heterocyclic chemoluminescent, preferably derivatives chosen from the group consisting of acridinium, substituted acridinium, phenanthridinium, substituted phenantridinium, quinolenium, substituted quinolenium, isoquinolenium and substituted isoquinolenium corresponding to formulas I IV times in Figure 1, in which:
- R x is H, a radical chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, optionally substituted, or a chain of formula [R ⁇ XR ⁇ ] n where n ⁇ 1 and X represents one or more heteroatoms, - R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 / R ⁇ o ' R n e R i2 are substituents which do not interfere with chemoluminescence (but which can modify it qualitatively and quantitatively), R 3 to R 12 are hydrogen or radicals chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, optionally substituted,
- R 2 is an amine, a hydroxylamine, a chaicogenolamine, an oxi e or an isostere of oxime, and their phosphorus, aesene and antimony analogs the radical or radicals of which are chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl arylalkyl, heteroaryl, heteroarylalkyl, acyl, arylacyl, hdisputedroarylacyle, alkylsulfonyl, alkénylsulfonyle, alkynylsulfonyle, arylsulfonyl, heteroarylsulfonyl, alkylsulfinyl, alkénylsulfinyle, alkynylsulfinyle arylsulfinyl, heteroarylsulfinyl, alkylsulfinyl, alkénylsul
- X and Y are elements chosen from the group consisting of 0, S, Se and Te and in which R 13 , R 14 and / or R 15 are radicals chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, optionally substituted, - or a chalcogenolamine of formula:
- - Z represents an element chosen from the group consisting of O, S, Se and Te,
- A represents an element chosen from the group consisting of N, P, As, Sb,
- X represents an element chosen from the group consisting of C, O, S, Se and Te,
- Y represents an element chosen from the group consisting of O, S, Se and Te and
- R 13 , R 14 and / or R 15 are radicals chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, optionally substituted, - either an oxime or an isostere of oxime and its phosphorous derivatives , arsenic and antimony of formula:
- X is an element chosen from the group consisting of N, P, As, Sb and C - R 15 and
- R 13 , R 14 and R 1S are radicals chosen from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, optionally substituted.
- R x is a methyl
- R 2 is an amine of formula: R 13
- R-_ is a methyl
- R 2 is an amine of formula:
- R 13 and R 14 are aryl or heteroaryl radicals, optionally substituted.
- R x is a methyl
- R 2 is an amine of formula:
- R 13 and R 14 are aryl or heteroaryl radicals, optionally substituted.
- R x is a methyl
- R 2 is a hydroxylamine or a chalcogenolamine of formula:
- - 'R I3 is an alkyl, aryl or heteroaryl radical, possibly substituted and
- R 14 is an acyl, alkylsulfonyl, arylsulfonyl or arylcarboxyl radical, optionally substituted.
- R 1 is a methyl
- R 2 is an oxime of formula:
- R 13 and R 14 are optionally substituted alkyl, aryl or heteroaryl radicals.
- the chemoluminescent derivatives are the compounds: N-phenyl-N- (N-methylpyr idinium -2 -yl) - 10 -methylacr idinium- 9 - carboxamide or
- conjugate comprising a chemoluminescent derivative according to the invention linked to a specific biological component.
- specific biological compound means any biological molecule (lipid, saccharide, protein, peptide, nucleic acid, ...) or set of biological molecules, specific to a species (viral, bacterial, plant, animal or other) , an individual, a pathology (such as cancer or caused by a viral, bacterial or other agent), an activity or a biochemical system (such as an enzymatic reaction, ).
- Said biological component is capable of being detected and / or measured, or capable of being used for assaying and / or detecting a specific biological component.
- this specific biological compound is chosen from the group consisting of antibodies, haptens, antigens, nucleic acids, agonists, cell transporters, fatty acids, lipids and / or a mixture of them.
- the present invention also relates to the diagnostic and / or assay kit comprising the conjugate or one of the chemoluminescent derivatives according to the invention and the use of the conjugate and / or of a chemoluminescent derivative according to the invention for the assay and / or the detection of a specific biological compound.
- the diagnostic and / or assay kit comprising the conjugate or one of the chemoluminescent derivatives according to the invention and the use of the conjugate and / or of a chemoluminescent derivative according to the invention for the assay and / or the detection of a specific biological compound.
- FIG. 1 represents the general formulas of the chemoluminescent derivatives according to the present invention.
- FIG. 2 represents the synthesis of the N-phenyl-N- iodomercurate (N-methylpyridinium-2-yl) -10- methylacridinium-9-carboxamide (BPACAM1) according to the invention.
- FIG. 3 represents the synthesis of the iodomercurate of N- (N 1 -hydroxysuccinimidylbenzoate-4-yl) -N-
- FIG. 4 represents the synthesis of the iodomercurate of N-pyridyl-N- (N-methylpyridinium-2-yl) -10- methylacridinium-9-carboxamide (PPACAM1) according to the invention.
- FIG. 5 represents the synthesis of the i o d o m e r c u r a t e of (N - hydroxysuccinimidylformylpropionanilide) -10-methylacridinium-9-carboxylate (FA6) according to the invention.
- FIG. 6 represents the synthesis of the i o d o m e r c u r a t e of (N - hydroxysuccinimidylformylpropioperfluoroanilide) -10 - methylacridinium-9-carboxylate (FA13) according to the invention.
- FIG. 7 represents the synthesis of the iodomercurate of 4 - (-methylsulfonamido- (N-hydroxysuccinimidyl) -benzoate) - 10 -methylacridinium-9 - carboxylate (SHA1) according to the invention.
- FIG. 8 represents the synthesis of 4- (N-perfluorophenylsulfonamido- (N-hydroxysuccinimidyl) -benzoate) - 10 -methylacridinium-9-carboxylate iodomercurate according to the invention.
- Figure 9 shows the synthesis of
- FIG. 10 represents the synthesis of the iodomercurate of (1- (N-hydroxysuccinimidylbenzoate-4-yl) -1-perfluorophenyl-1-iminomethane) -10-methylacridinium-9 - carboxylate (FA12) according to the invention.
- FIG. 12 represents the synthesis of the iodomercurate of 4 - (N-phenylsulfonamido - (N-hydroxysuccinimidyl) ' -benzoate) -10 -methylacridinium-9 - carboxylate (SHA2) according to the invention.
- FIG. 13 represents a comparative study of the stability of FA6, FA10 and DMAE (measurement of chemoluminescence as a function of time).
- Figures 14 to 29 show the mass spectra of the products of the invention.
- Figures 30 to 47 show the infrared spectra of the products of the invention.
- EXAMPLE 1 SYNTHESIS OF BPACAM1 (fi ⁇ . 2).
- the acid chloride is suspended in 40 ml of anhydrous tetrahydrofuran (THF) containing three equivalents of triethylamine (Et 3 N). The mixture is stirred, and 1.52 g of
- EXAMPLE 2 SYNTHESIS OF BPCAM3. (fia. 3).
- the purification of product III is carried out by solubilization of the acid in basic medium, passage over active carbon and reprecipitation in acid medium.
- EXAMPLE 3 SYNTHESIS OF PPACAM1. (fia. 4)
- Product III is isolated from the solution by precipitation with petroleum ether (100/140).
- N-phenylhvdroxylamine 500 ml of water, 25 g of ammonium chloride (NH 4 C1) are placed in a 2-liter berlin and 50 g of nitrobenzene (I). This mixture is mechanically stirred and 62 g of powdered zinc are added in portions to the solution. After 15 minutes the solution heats up and the rest of the zinc (about 30 g) is carefully added to the solution. The temperature of the reaction mixture is between 65 and 80 ° C throughout the duration of the reduction.
- the solution is filtered to remove the zinc oxide.
- the filtrate is then saturated with NaCl and cooled as quickly as possible to 0 ° C.
- the N-phenylhydroxylamine (II) which crystallizes from the solution is isolated by filtration and freed from nitrobenzene which may be present by washing with petroleum ether.
- the product is then dried over P 2 O s and stored under nitrogen at -20 ° C.
- product VI 1 g is dissolved in 30 ml of anhydrous dioxane. To this solution, 0.23 g of N-hydroxysuccinimide (NHS) and 0.41 g of dicyclohexylcarbodiimide (DCC) are added. The disappearance of product VI is followed by thin layer chromatography. When the reaction is complete, the dicyclohexylurea formed is removed by filtration and the solvent distilled under reduced pressure. The residue is taken up in 10 ml of ethyl acetate to precipitate the remaining dicyclohexylurea. The product (VII) is purified by chromatography on a silica column, the mobile phase being a mixture of toluene and ethyl acetate (v / v: 2: 1).
- EXAMPLE 6 SYNTHESIS OF SHA1 (Fi ⁇ 7). Iodomercurate of 4- (N-methylsulfonamido - (N- hydroxysuccinimidyl) -benzoate) - 10 -methylacridinium-9 - carboxylate
- EXAMPLE 8 SYNTHESIS OF SHA3 (Fi ⁇ . 8).
- the N-perfluorophenylhydroxylamine (II) crystallizes from the solution. It is isolated by filtration and dried under vacuum. The product is stored under nitrogen at -20 ° C.
- the residue is dissolved in chloroform, the chloroform phase is washed with water and dried over anhydrous sodium sulfate.
- the crude product (IV) is obtained after evaporation of the solvent on a rotary evaporator.
- the pure product is obtained by recrystallization from toluene.
- EXAMPLE 10 SYNTHESIS OF FA12 (Fig. 10). (1- (N-hydroxysuccinimidylbenzoate-4-yl) -1- perfluorophenyl-1-iminomethane) -10 -methylacridinium-9-carboxylate iodomercurate
- the residue is taken up in 10 ml of ethyl acetate to precipitate the remaining dicyclohexylurea.
- the product (VII) is purified by chromatography on a silica column, the mobile phase consisting of a mixture of toluene and ethyl acetate (v / v: 4: 1).
- a solution of chloramine (IV) is also prepared by reaction of 2 g of diethylamine dissolved in 10 ml of ice water with 5.5 ml of ice cold solution of sodium hypochlorite with 13% active chlorine.
- EXAMPLE 12 CHEMOLUMINESCENCE TESTS.
- the derivatives having, like the products of the invention, a leaving group Y, with a pKa greater than that of hydrogen peroxide (pKa> 12) would not give a sufficient chemoluminescent signal.
- Table I shown on the next page gives the values obtained by integration of the chemoluminescent signal caused by chemical reaction between the substance and hydrogen peroxide in an alkaline medium. It also provides the approximate pKa values of the leaving group Y of the substances tested.
- substances (1) and (2) give very weak signals. This is easily explained by the values of pKa which are much higher than that of H 2 0 2 .
- the phenolic ester DMAE-NHS produces a high chemoluminescence which can be explained by a relatively low pKa value.
- FA6 generates a higher concentration of luninecence at a higher concentration than that of acridinium phenol esters, but when the quantity used is less than 10 "14 mole, the signal given by FA6 is higher and this effect is even more marked when the quantities are reduced further; on the other hand, the linear response extends for FA6 over almost 6 orders of magnitude while it is limited to four in the case of the phenolic esters d 'acridinium.
- SHA1 The marked difference between SHA1 and FA5 would be linked to the replacement of the carboxyl of FA5 by a sulfonyl more sensor in SHA1.
- EXAMPLE 13 DETERMINATION OF TSH USING AN ANTIBODY MARKED BY
- the elution is monitored by measuring the luminescence of the fractions and the fraction corresponding to molecular weights between 100,000 and 200,000 is collected and characterized by a high luminescent power.
- the collected solution is concentrated on an ultrafiltering membrane and the absence of luminescent products in the ultrafiltrate is checked.
- the samples are prepared in a similar way to the calibration curve, but replacing the standards by them will be to be dosed.
- the supernatant present in the standards and the samples is removed by aspiration. 2 ml of washing solution are added to each tube (0.1 M phosphate buffer 0.5 M NaCl adjusted to pH 7.4; protein and detergent). It is left to act for one minute and then the solution is aspirated. We repeat the procedure.
- the tubes are introduced into the luminometer which performs the measurement and the automated addition of the reagents (300 ⁇ l of 0.1 M nitric solution of 0.5% hydrogen peroxide followed by 300 ⁇ l of 0.25 M hydroxide solution sodium.
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Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU15292/95A AU1529295A (en) | 1994-01-25 | 1995-01-25 | Heterocyclic chemoluminescent derivatives |
EP95906853A EP0741720A1 (fr) | 1994-01-25 | 1995-01-25 | Derives chemoluminescents heterocycliques |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BE9400087A BE1008216A4 (fr) | 1994-01-25 | 1994-01-25 | Derives chemoluminescents heterocycliques. |
BE9400087 | 1994-01-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995019976A1 true WO1995019976A1 (fr) | 1995-07-27 |
Family
ID=3887915
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/BE1995/000007 WO1995019976A1 (fr) | 1994-01-25 | 1995-01-25 | Derives chemoluminescents heterocycliques |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0741720A1 (fr) |
AU (1) | AU1529295A (fr) |
BE (1) | BE1008216A4 (fr) |
WO (1) | WO1995019976A1 (fr) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056765A1 (fr) * | 1997-06-11 | 1998-12-17 | Biocode S.A. | Derives chimioluminescents heterocycliques |
WO2002099097A1 (fr) * | 2001-06-01 | 2002-12-12 | Roche Diagnostics Gmbh | Nouveaux composes destines a des procedes de chimioluminescence |
WO2005015215A1 (fr) * | 2003-07-30 | 2005-02-17 | Roche Diagnostics Gmbh | Nouveaux composes chimioluminescents et leur utilisation |
US7262306B2 (en) | 2003-07-08 | 2007-08-28 | Roche Diagnostics Operations, Inc. | Chemiluminescent compounds and their use |
WO2008035359A2 (fr) * | 2006-06-12 | 2008-03-27 | Cadila Healthcare Limited | Acide oxyminophénoxyalcanoïque et dérivés de l'acide phenylalcanoïque |
US7695980B2 (en) | 2003-07-30 | 2010-04-13 | Roche Diagnostics Operations, Inc. | Chemiluminescent compounds and their use |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0257541A2 (fr) * | 1986-08-22 | 1988-03-02 | Hoechst Aktiengesellschaft | Dérivés de l'acridine chimioluminescents et leur utilisation pour dosage immunologique par chimioluminescence |
EP0273115A2 (fr) * | 1986-10-22 | 1988-07-06 | Abbott Laboratories | Sels d'acridines et de phénantridines chimiluminescents |
EP0330050A2 (fr) * | 1988-02-20 | 1989-08-30 | Hoechst Aktiengesellschaft | Dérivés spéciaux d'acridine chimiluminescents et leur utilisation dans des tests d'immunoluminescence |
WO1992009580A1 (fr) * | 1990-11-21 | 1992-06-11 | Beckman Instruments, Inc. | Composes chimioluminescents |
JPH05255264A (ja) * | 1992-03-13 | 1993-10-05 | Sanyo Chem Ind Ltd | 標識剤および標識されたリガンドの製法 |
-
1994
- 1994-01-25 BE BE9400087A patent/BE1008216A4/fr not_active IP Right Cessation
-
1995
- 1995-01-25 AU AU15292/95A patent/AU1529295A/en not_active Abandoned
- 1995-01-25 WO PCT/BE1995/000007 patent/WO1995019976A1/fr not_active Application Discontinuation
- 1995-01-25 EP EP95906853A patent/EP0741720A1/fr not_active Withdrawn
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0257541A2 (fr) * | 1986-08-22 | 1988-03-02 | Hoechst Aktiengesellschaft | Dérivés de l'acridine chimioluminescents et leur utilisation pour dosage immunologique par chimioluminescence |
EP0273115A2 (fr) * | 1986-10-22 | 1988-07-06 | Abbott Laboratories | Sels d'acridines et de phénantridines chimiluminescents |
EP0330050A2 (fr) * | 1988-02-20 | 1989-08-30 | Hoechst Aktiengesellschaft | Dérivés spéciaux d'acridine chimiluminescents et leur utilisation dans des tests d'immunoluminescence |
WO1992009580A1 (fr) * | 1990-11-21 | 1992-06-11 | Beckman Instruments, Inc. | Composes chimioluminescents |
JPH05255264A (ja) * | 1992-03-13 | 1993-10-05 | Sanyo Chem Ind Ltd | 標識剤および標識されたリガンドの製法 |
Non-Patent Citations (1)
Title |
---|
PATENT ABSTRACTS OF JAPAN vol. 18, no. 19 (C - 1152) 13 January 1994 (1994-01-13) * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056765A1 (fr) * | 1997-06-11 | 1998-12-17 | Biocode S.A. | Derives chimioluminescents heterocycliques |
BE1011206A4 (fr) * | 1997-06-11 | 1999-06-01 | Biocode Sa | Derives chimioluminescents heterocycliques. |
WO2002099097A1 (fr) * | 2001-06-01 | 2002-12-12 | Roche Diagnostics Gmbh | Nouveaux composes destines a des procedes de chimioluminescence |
US7332354B2 (en) | 2001-06-01 | 2008-02-19 | Roche Diagnostics Operations, Inc. | Compounds for chemiluminescense procedures |
US7262306B2 (en) | 2003-07-08 | 2007-08-28 | Roche Diagnostics Operations, Inc. | Chemiluminescent compounds and their use |
WO2005015215A1 (fr) * | 2003-07-30 | 2005-02-17 | Roche Diagnostics Gmbh | Nouveaux composes chimioluminescents et leur utilisation |
US7563902B2 (en) | 2003-07-30 | 2009-07-21 | Roche Diagnostics Operations, Inc. | Chemiluminescent compounds and their use |
US7695980B2 (en) | 2003-07-30 | 2010-04-13 | Roche Diagnostics Operations, Inc. | Chemiluminescent compounds and their use |
WO2008035359A2 (fr) * | 2006-06-12 | 2008-03-27 | Cadila Healthcare Limited | Acide oxyminophénoxyalcanoïque et dérivés de l'acide phenylalcanoïque |
WO2008035359A3 (fr) * | 2006-06-12 | 2008-05-15 | Cadila Healthcare Ltd | Acide oxyminophénoxyalcanoïque et dérivés de l'acide phenylalcanoïque |
Also Published As
Publication number | Publication date |
---|---|
BE1008216A4 (fr) | 1996-02-20 |
AU1529295A (en) | 1995-08-08 |
EP0741720A1 (fr) | 1996-11-13 |
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