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DE19645974C1 - (Z) -5 - [[3-Hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone, process for its preparation and use - Google Patents

(Z) -5 - [[3-Hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone, process for its preparation and use

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Publication number
DE19645974C1
DE19645974C1 DE19645974A DE19645974A DE19645974C1 DE 19645974 C1 DE19645974 C1 DE 19645974C1 DE 19645974 A DE19645974 A DE 19645974A DE 19645974 A DE19645974 A DE 19645974A DE 19645974 C1 DE19645974 C1 DE 19645974C1
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methyl
thiazolidinone
thioxo
phosphonooxy
pyridinyl
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Andreas Johannes Kesel
Walter Dr Oberthuer
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Priority to DE19645974A priority Critical patent/DE19645974C1/en
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Priority to TR1999/01733T priority patent/TR199901733T2/en
Priority to BRPI9712930-5A priority patent/BR9712930A/en
Priority to PCT/EP1997/006184 priority patent/WO1998020013A1/en
Priority to KR1019990704073A priority patent/KR20000053141A/en
Priority to JP52107198A priority patent/JP2001503752A/en
Priority to PL97333128A priority patent/PL333128A1/en
Priority to CN97199496A priority patent/CN1236369A/en
Priority to HU9904289A priority patent/HUP9904289A3/en
Priority to CZ991609A priority patent/CZ160999A3/en
Priority to AU54798/98A priority patent/AU728345B2/en
Priority to SK617-99A priority patent/SK61799A3/en
Priority to IL12982697A priority patent/IL129826A0/en
Priority to CA002270973A priority patent/CA2270973A1/en
Priority to EP97951145A priority patent/EP0937089A1/en
Priority to NZ335977A priority patent/NZ335977A/en
Priority to DE19819820A priority patent/DE19819820A1/en
Application granted granted Critical
Publication of DE19645974C1 publication Critical patent/DE19645974C1/en
Priority to NO992209A priority patent/NO992209L/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
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    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

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Description

Es wurde nach einer Verbindung gesucht, die an einzelsträngige Nucleinsäure binden kann und sich von einem Naturstoff ableitet, der biochemisch relevant ist.A compound has been sought that can bind to single-stranded nucleic acid and is derived from a natural product that is biochemically relevant.

Es ist daher Aufgabe der Erfindung, ein Hilfsmittel für den Nachweis, und/oder die Analyse und/oder elektrophoretische Trennung von einzelsträngiger Nucleinsäure bereitzustellen. Darüber hinaus soll die Erfindung als Therapieprinzip von Krankheiten dienen, deren infektiöse Erreger sich im Wirt über Zwischenstufen mit einzelsträngiger Nucleinsäure vermehren. Die Aufgabe wird gelöst durch die Synthese von 3.It is therefore an object of the invention to be an aid for detection and / or analysis and / or to provide electrophoretic separation of single-stranded nucleic acid. About that In addition, the invention is intended to serve as a therapeutic principle for diseases, their infectious agents multiply in the host via intermediates with single-stranded nucleic acid. The task is solved by the synthesis of 3.

Bei der Substanz 3 handelt es sich um ein Derivat des Vitamin B6-Coenzymes Pyridoxal-5'- phosphat 1. Es wird mit dem synthetischen Heterocyclus Rhodanin 2 (2-Thioxo-4-thiazolidinon) in einer Knoevenagel-Kondensation umgesetzt.
Substance 3 is a derivative of the vitamin B 6 coenzyme pyridoxal-5'-phosphate 1. It is reacted with the synthetic heterocycle rhodanine 2 (2-thioxo-4-thiazolidinone) in a Knoevenagel condensation.

Die Verbindung 3 trägt den Namen (Z)-5-[[3-Hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4- pyridinyl]methylen]-2-thioxo-4-thiazolidinon, oder trivial benannt (Z)-5'-O-phosphono­ pyridoxylidenrhodanin. Der Rhodanin-Teil des Moleküls vermittelt die Bindungsfähigkeit an einzelsträngige Nucleinsäure. Die Phosphat-Gruppe sorgt für gute Wasserlöslichkeit der Verbindung 3.Compound 3 is named (Z) -5 - [[3-hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4- pyridinyl] methylene] -2-thioxo-4-thiazolidinone, or trivially named (Z) -5'-O-phosphono pyridoxylidene rhodanine. The rhodanine part of the molecule conveys the binding ability  single-stranded nucleic acid. The phosphate group ensures good water solubility Connection 3.

Die Verbindung 3 unterliegt einer (Z/E)-Stereoisomerie zum (E)-Isomeren 4. Die Bindung an die Kernbase Adenin unter Bildung eines Komplexes konnte wahrscheinlich gemacht werden.
Compound 3 undergoes a (Z / E) stereoisomerism to the (E) isomer 4. Binding to the core base adenine to form a complex could probably be made.

Die Analytik der Verbindung 3 umfaßt 1H-NMR-Spektroskopie, 13C-NMR-Spektroskopie, 31P-NMR-Spektroskopie, RP-18 HPLC, Fast Atom Bombardment Massenspektrometrie (FAB MS), IR-Spektroskopie, UV-Spektrophotometrie und Fluoreszenzspektrophotometrie. Es folgen typische analytische Daten der Verbindung 3:
C11 H11 N2 O6 P S2, M = 362.31 g/mol. FAB MS (MH+ berechnet für m/z 362.99): m/z (rel.Int.) 363.0 (12.0%, MH+), 227.4 (18.1%), 270.4 (8.7%), 171.2 (8.3%), 282.4 (7.1%), 267.1 (2.8%), 283.4 (2.1%), 265.1 (1.5%). 1H NMR (TFA-d): δ 2.91 (s, 3 H, 2'-CH3), 5.42 (d,|3J(31P,1H)| = 8.0 Hz, 2 H, 5'-CH2-OPO3H2), 7.76 (s, 1 H, 4'-CH), 8.47 (s, 1 H, 6-CH). 13C NMR, BB-entkoppelt (TFA-d): δ 16.83 (s, 2'-CH3), 65.75 (s, 5'-CH2-OPO3H2), 121.04, 122.13 (2 s, C-4'), 133.34 (s, C-6), 136.85, 136.91 (2 s, RR'C-SR''), 138.54 (s, C-5), 142.05 (s, C-4), 147.64 (s, C-2), 153.03 (s, C-3), 171.93 (s, C = O), 193.39 (S, C = S). 31P NMR (TFA-d): δ - 4.24 (s, R-OPO3H2). UV/VIS (H2O): λmax,1 = 300-304 nm [E (1%/1 cm) = 250-270], λmax,2 = 346-358 nm [E (1%/1 cm) = 380-410], λmax,3 = 446-450 nm [E (1%/1 cm) = 220-240].The analysis of compound 3 includes 1 H-NMR spectroscopy, 13 C-NMR spectroscopy, 31 P-NMR spectroscopy, RP-18 HPLC, Fast Atom Bombardment Mass Spectrometry (FAB MS), IR spectroscopy, UV spectrophotometry and fluorescence spectrophotometry . Typical analytical data of compound 3 follow:
C 11 H 11 N 2 O 6 PS 2 , M = 362.31 g / mol. FAB MS (MH + calculated for m / z 362.99): m / z (rel.Int.) 363.0 (12.0%, MH + ), 227.4 (18.1%), 270.4 (8.7%), 171.2 (8.3%), 282.4 (7.1%), 267.1 (2.8%), 283.4 (2.1%), 265.1 (1.5%). 1 H NMR (TFA-d): δ 2.91 (s, 3 H, 2'-CH 3 ), 5.42 (d, | 3 J ( 31 P, 1 H) | = 8.0 Hz, 2 H, 5'-CH 2 -OPO 3 H 2 ), 7.76 (s, 1 H, 4'-CH), 8.47 (s, 1 H, 6-CH). 13 C NMR, BB-decoupled (TFA-d): δ 16.83 (s, 2'-CH 3 ), 65.75 (s, 5'-CH 2 -OPO 3 H 2 ), 121.04, 122.13 (2 s, C- 4 '), 133.34 (s, C-6), 136.85, 136.91 (2 s, RR'C-SR''), 138.54 (s, C-5), 142.05 (s, C-4), 147.64 (s , C-2), 153.03 (s, C-3), 171.93 (s, C = O), 193.39 (S, C = S). 31 P NMR (TFA-d): δ - 4.24 (s, R-OPO 3 H 2 ). UV / VIS (H 2 O): λ max, 1 = 300-304 nm [E (1% / 1 cm) = 250-270], λ max, 2 = 346-358 nm [E (1% / 1 cm ) = 380-410], λ max, 3 = 446-450 nm [E (1% / 1 cm) = 220-240].

Beispiel 1.) HerstellungsverfahrenExample 1.) Manufacturing process

Man löst 3,83 g 2-Thioxo-4-thiazolidinon (Rhodanin) (M = 133,18 g/mol; n = 28,76 mmol) in 150 ml absolutem Ethanol in einem 50 ml NS29/32 Rundkolben mit Rückflußkühler und gibt 7,63 g Pyridoxal-5'-phosphat-monohydrat (M= 265,16 g/mol; n = 28,78 mmol) hinzu. Das Pyridoxal-5'- phosphat-monohydrat löst sich in der Kälte fast nicht.3.83 g of 2-thioxo-4-thiazolidinone (rhodanine) (M = 133.18 g / mol; n = 28.76 mmol) are dissolved in 150 ml of absolute ethanol in a 50 ml NS29 / 32 round bottom flask with reflux condenser and gives 7.63 g Pyridoxal-5'-phosphate monohydrate (M = 265.16 g / mol; n = 28.78 mmol) was added. The pyridoxal-5'- phosphate monohydrate almost does not dissolve in the cold.

Man kocht auf dem Wasserbad mit einem Siedesteinchen am Rückfluß. Das Pyridoxal-5'- phosphat-monohydrat geht nun langsam in Lösung und eine zunächst gelbe, dann orange, dann rote Suspension entsteht. Nach 20 min Sieden gibt man durch den Kühler 150 ml Wasser zu, weil die Suspension aufzustoßen beginnt. Man erwärmt noch 20 min, wobei das rote Reaktionsprodukt ausfällt und zum Aufstoßen führt. Danach kühlt man nicht mehr als 3 Stunden im Gefrierfach bei einer Temperatur von -18°C.You cook on the water bath with a boiling stone at reflux. The pyridoxal-5'- Phosphate monohydrate now slowly goes into solution and an initially yellow, then orange, then red suspension is formed. After boiling for 20 minutes, 150 ml of water are added through the cooler because the suspension begins to belch. The mixture is heated for a further 20 min, the red reaction product fails and leads to belching. After that, do not chill in the freezer for more than 3 hours a temperature of -18 ° C.

Auf diese Weise erhält man die zunächst orange (Z/E)-Mischform der Verbindung, in der das (Z)-Stereoisomer bei weitem überwiegt. Wenn lange bei Anwesenheit von Wasser gekühlt wird oder das orange (Z/E)-Produkt in Wasser länger aufgekocht wird, geht die orange Mischform ganz in das gelbe (Z)-Stereoisomer über.In this way, the initially orange (Z / E) mixed form of the compound is obtained, in which the (Z) stereoisomer by far outweighs. When cooling in the presence of water for a long time or the orange (Z / E) product is boiled in water for a longer time, the orange mixed form is completely gone into the yellow (Z) stereoisomer.

AufarbeitungRefurbishment

Das orange Produkt wird abgesaugt, mit der Mutterlauge überführt und mit 100 ml eiskaltem abs. Ethanol gewaschen. Vakuumtrocknung im Exsikkator über wfr. Calciumchlorid (CaCl2); Ausbeute: 9,5 g (91%, bezogen auf wasserfreie Substanz) orangegelbes, feinkristallines Pulver (Z)-5-[[3-Hydroxy-2-methyl-5-[(phosphonooxy)methyl)-4-pyridinyl]methylen]-2-thioxo-4- thiazolidinon, Gehalt w < 96% (1H-NMR, RP 18 - HPLC, bezogen auf wasserfreie und alkoholfreie Substanz), das Produkt enthält trotz Vakuumtrocknung Ethanol und Wasser.The orange product is filtered off, transferred with the mother liquor and with 100 ml of ice-cold abs. Washed ethanol. Vacuum drying in a desiccator over wfr. Calcium chloride (CaCl 2 ); Yield: 9.5 g (91%, based on anhydrous substance) of orange-yellow, finely crystalline powder (Z) -5 - [[3-hydroxy-2-methyl-5 - [(phosphonooxy) methyl) -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone, content w <96% ( 1 H-NMR, RP 18 - HPLC, based on anhydrous and alcohol-free substance), the product contains ethanol and water despite vacuum drying.

Beispiel 2.) Nachweisverfahren für einzelsträngige NucleinsäurenExample 2.) Detection method for single-stranded Nucleic acids

Die Substanz 3 soll in radioaktiv markierter (32P oder 35S) Form als Sonde für einzelsträngige Nucleinsäure dienen. In radioactively labeled ( 32 P or 35 S) form, substance 3 is said to serve as a probe for single-stranded nucleic acid.

Beispiel 3.) Zweidimensionale Nucleinsäure- ElektrophoreseExample 3.) Two-dimensional nucleic acid Electrophoresis

Die Substanz 3 soll in radioaktiv unmarkierter/markierter Form als Hilfsmittel für die elektrophoretische Trennung einzelsträngiger Nucleinsäure dienen.Substance 3 is said to be in radioactive, unlabelled / labeled form as an aid for serve electrophoretic separation of single-stranded nucleic acid.

Beispiel 4.) Photochemische kovalente Fixierung der nichtkovalenten Bindung von 3/4 an einzelsträngige DNA durch Bestrahlung mit UV-LichtExample 4.) Photochemical covalent fixation of the 3/4 noncovalent binding to single-stranded DNA by irradiation with UV light

Die nichtkovalent bindende Form 3 oder 4 in bezug auf einzelsträngige DNA kann durch Bestrahlung mit UV-Licht der Wellenlänge 366 nm oder 254 nm photochemisch fixiert werden. Dabei reagiert 3/4 mit einer Thymin-Kernbasen-Methylgruppe photochemisch unter Abspaltung von Schwefelwasserstoff.
The noncovalently binding form 3 or 4 with respect to single-stranded DNA can be fixed photochemically by irradiation with UV light of the wavelength 366 nm or 254 nm. 3/4 reacts photochemically with a thymine core base methyl group with elimination of hydrogen sulfide.

Beispiel 5.) Fluoreszenzdetektion von ssDNAExample 5.) Fluorescence detection of ssDNA

Die Substanz 3 soll aufgrund seiner (Z/E)-Stereoisomerie als Hilfsmittel für die Fluoreszenzdetektion einzelsträngiger DNA dienen. Das (E)-Stereoisomer 4 fluoresziert in DMSO, das (Z)-Stereoisomer in Wasser wesentlich weniger. Angenommen wird, daß die an einzelsträngige DNA bindende Form das (E)-Stereoisomere 4 ist. Dadurch kann bei auftretender Fluoreszenz nach Extraktion mit DMSO einzelsträngige DNA nachgewiesen werden.Due to its (Z / E) stereoisomerism, substance 3 is said to be an aid for Fluorescence detection of single-stranded DNA are used. The (E) stereoisomer 4 fluoresces in DMSO, the (Z) stereoisomer in water, significantly less. It is assumed that the single-stranded DNA binding form that is (E) stereoisomer 4. This can result in Fluorescence can be detected after extraction with DMSO single-stranded DNA.

Beispiel 6.) Therapeutische AnwendungExample 6.) Therapeutic application

Die Substanz 3 soll als therapeutisches Hilfsmittel für die Beeinflussung von Vermehrungsvorgängen von infektiösen Erregern dienen, die im Wirt mit Zwischenstufen einzelsträngiger DNA ablaufen, z. B. Retroviren oder das Hepatitis-B-Virus.Substance 3 is said to be a therapeutic tool for influencing Propagation processes of infectious pathogens serve in the host with intermediate stages run single-stranded DNA, z. B. retroviruses or the hepatitis B virus.

Beispiel 7.) Temperatur/Lösungmittel-IndikatorExample 7.) Temperature / solvent indicator

Die (Z/E)-Stereoisomerie von 3 kann abhängig von der Temperatur (Thermochromie) und abhängig vom Lösungsmittel (Solvatochromie) auftreten. Daher kann 3 als Temperaturindikator und/oder Lösungsmittelindikator dienen.The (Z / E) stereoisomerism of 3 can depend on the temperature (thermochromism) and depending on the solvent (solvatochromism). Therefore 3 can be used as a temperature indicator and / or serve as a solvent indicator.

Beispiel 8.) Digitale Schaltfunktion der (Z/E)- Stereoisomeren 3/4Example 8.) Digital switching function of the (Z / E) - Stereoisomers 3/4

Die (Z/E)-Stereoisomerie von 3 gegenüber 4 kann abhängig vom Anlegen eines elektrischen Feldes auftreten (Elektrochromie). Daher kann 3 als digitales Schaltelement aufgrund der unterschiedlichen fluoreszenzspektrophotometrischen Eigenschaften von 3 gegenüber 4 z. B. bei der Anregung durch Laserlicht der Wellenlänge 480 nm dienen. Dabei tritt nach Anlegen eines elektrischen Feldes an 3 Umlagerung in 4 und damit Fluoreszenemission bei 575 nm durch Exzitation bei 480 nm auf.The (Z / E) stereoisomerism of 3 versus 4 can depend on the application of an electrical one Field (electrochromism). Therefore 3 can be used as a digital switching element due to the different fluorescence spectrophotometric properties of 3 versus 4 z. B. at serve for excitation by laser light with a wavelength of 480 nm. This occurs after creating a electric field at 3 rearrangement in 4 and thus fluorescence emission at 575 nm Excitation at 480 nm.

Beispiel 9.) Vitamin B6-AntagonismusExample 9.) Vitamin B 6 antagonism

Die Verbindung 3 kann im Stoffwechsel als Antagonist des Coenzymes Pyridoxal-5'-phosphat wirken und deshalb eventuell tumorhemmende Eigenschaften aufweisen.Compound 3 can act as an antagonist of the coenzyme pyridoxal-5'-phosphate in metabolism act and therefore may have anti-tumor properties.

Beispiel 10.) ProliferationskontrolleExample 10.) Proliferation control

Die Verbindung 3 kann eventuell zur Proliferationskontrolle/Chemotherapie/Zytostasetherapie von malignen Tumoren in lokaler Applikation auf Hauttumore (malignes Melanom) in Verbindung mit UV-Bestrahlung dienen und/oder zur Proliferationskontrolle von anderen Hautkrankheiten mit erhöhter Zellteilungsrate dienen (z. B. Psoriasis). Dabei wird die Bindung an replikationsaktive einzelsträngige DNA-Bereiche durch UV-Bestrahlung photochemisch fixiert und führt zu lokal begrenzter Zytotoxizität.Compound 3 may be used for proliferation control / chemotherapy / cytostatic therapy of malignant tumors in local application on skin tumors (malignant melanoma) in Used in conjunction with UV radiation and / or for the proliferation control of others Skin diseases with an increased cell division rate serve (e.g. psoriasis). This binds to Replication-active single-stranded DNA areas fixed photochemically by UV irradiation and leads to localized cytotoxicity.

Claims (3)

1. (Z)-5-[[3-Hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methylen]-2-thioxo-4- thiazolidinon der Formel 3.
1. (Z) -5 - [[3-hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone of the formula 3.
2. Verfahren zur Herstellung der Verbindung gemäß Anspruch 1, dadurch gekennzeichnet, daß man Pyridoxal-5'-phosphat mit Rhodanin in einer Knoevenagel-Kondensation umsetzt.2. A method for producing the compound according to claim 1, characterized in that reacting pyridoxal-5'-phosphate with rhodanine in a Knoevenagel condensation. 3. Verwendung der Verbindung gemäß Anspruch 1 als Komplexierungsmittel in der Analytik zum Nachweis/therapeutischen Nachweis von einzelsträngiger Nucleinsäure, insbesondere DNA, zur Therapie von Infektionen mit Erregern, die sich im Wirt über einzelsträngige DNA vermehren, sowie als Molekulardigitale Schalter unter Ausnutzung der unterschiedlichen Fluoreszenz­ eigenschaften der geometrischen Isomeren.3. Use of the compound according to claim 1 as a complexing agent in analysis for Detection / therapeutic detection of single-stranded nucleic acid, in particular DNA, for Therapy of infections with pathogens that multiply in the host via single-stranded DNA, as well as molecular digital switches using the different fluorescence properties of geometric isomers.
DE19645974A 1996-11-07 1996-11-07 (Z) -5 - [[3-Hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone, process for its preparation and use Expired - Fee Related DE19645974C1 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
DE19645974A DE19645974C1 (en) 1996-11-07 1996-11-07 (Z) -5 - [[3-Hydroxy-2-methyl-5 - [(phosphonooxy) methyl] -4-pyridinyl] methylene] -2-thioxo-4-thiazolidinone, process for its preparation and use
IL12982697A IL129826A0 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products method for their production and their use
PCT/EP1997/006184 WO1998020013A1 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
KR1019990704073A KR20000053141A (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
JP52107198A JP2001503752A (en) 1996-11-07 1997-11-07 Novel Knebena gel condensation product, its preparation and use
PL97333128A PL333128A1 (en) 1996-11-07 1997-11-07 New products of knoevenagel's condensation, method of manufacturing of them and their applications
CN97199496A CN1236369A (en) 1996-11-07 1997-11-07 New Knoevenagel condensation products, method for their production and use
HU9904289A HUP9904289A3 (en) 1996-11-07 1997-11-07 Pyridines substituted by heterocyclic groups, method for their production and pharmaceutical compositions containing the same
TR1999/01733T TR199901733T2 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, their production method and use.
AU54798/98A AU728345B2 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
SK617-99A SK61799A3 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
BRPI9712930-5A BR9712930A (en) 1996-11-07 1997-11-07 knoevenagel condensation products, processes for their preparation and application
CA002270973A CA2270973A1 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
EP97951145A EP0937089A1 (en) 1996-11-07 1997-11-07 New knoevenagel condensation products, method for their production and their use
NZ335977A NZ335977A (en) 1996-11-07 1997-11-07 Pyridine derivatives which are knoevenagel condensation products
CZ991609A CZ160999A3 (en) 1996-11-07 1997-11-07 Novel knoevenagel condensation products, processes of their preparation and their use
DE19819820A DE19819820A1 (en) 1996-11-07 1998-05-04 Mono-, oligo-, and polymeric Knoevenagel condensation products useful e.g. in pharmaceuticals, cosmetics and assay procedures
NO992209A NO992209L (en) 1996-11-07 1999-05-06 New Knoevenagel condensation products, processes for their preparation and their use

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CA2330811A1 (en) * 1998-05-04 1999-11-11 Andreas Johannes Kesel Monomeric, oligomeric and polymeric knoevenagel condensation products
IL141456A0 (en) * 1998-08-21 2002-03-10 Viropharma Inc Rhodanine derivatives and pharmaceutical compositions containing the same
CA2371653A1 (en) * 1999-04-30 2000-11-09 Walter Oberthur Antioxidative vitamin b6 analogs
US20030071780A1 (en) * 2001-10-16 2003-04-17 Vincent Kent D. High resolution display
US6940497B2 (en) 2001-10-16 2005-09-06 Hewlett-Packard Development Company, L.P. Portable electronic reading apparatus

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CN1236369A (en) 1999-11-24
NO992209L (en) 1999-07-01
WO1998020013A1 (en) 1998-05-14
NZ335977A (en) 2000-12-22
AU728345B2 (en) 2001-01-04
NO992209D0 (en) 1999-05-06
AU5479898A (en) 1998-05-29
JP2001503752A (en) 2001-03-21
IL129826A0 (en) 2000-02-29
CA2270973A1 (en) 1998-05-14
CZ160999A3 (en) 1999-09-15
SK61799A3 (en) 2000-01-18
TR199901733T2 (en) 1999-09-21
KR20000053141A (en) 2000-08-25
HUP9904289A3 (en) 2001-08-28
EP0937089A1 (en) 1999-08-25
BR9712930A (en) 2006-04-18
PL333128A1 (en) 1999-11-22

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