[go: up one dir, main page]

EP0000126B1 - Glucofuranosid-6-yl-Nitrosoharnstoffderivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel - Google Patents

Glucofuranosid-6-yl-Nitrosoharnstoffderivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel Download PDF

Info

Publication number
EP0000126B1
EP0000126B1 EP78100115A EP78100115A EP0000126B1 EP 0000126 B1 EP0000126 B1 EP 0000126B1 EP 78100115 A EP78100115 A EP 78100115A EP 78100115 A EP78100115 A EP 78100115A EP 0000126 B1 EP0000126 B1 EP 0000126B1
Authority
EP
European Patent Office
Prior art keywords
methyl
substituted
ethyl
deoxy
halogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP78100115A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0000126A1 (de
Inventor
Jaroslav Dr. Stanek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Ciba Geigy AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG
Publication of EP0000126A1 publication Critical patent/EP0000126A1/de
Application granted granted Critical
Publication of EP0000126B1 publication Critical patent/EP0000126B1/de
Priority to KE356085A priority Critical patent/KE3560A/xx
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/12—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention relates to new N 1 -glucofuranosid-6-yJ-N 2 nitrosoureas of the formula wherein R, and R 2 are hydrogen, optionally substituted alkyl by free or etherified hydroxy or halogen or optionally substituted by lower alkyl, free or etherified hydroxy, halogen or trifluoromethyl aralkyl or acyl, R, and R 2 together also represent alkylidene or cycloalkylidene, R 3 and R 5 optionally substituted by free or etherified hydroxy groups or halogen alkyl or optionally substituted by lower alkyl, free or etherified hydroxy, halogen or trifluoromethyl aralkyl or acyl, R 3 and R 5 together also mean alkylidene or cycloalkylidene, and R 6 optionally by free or etherified hydroxy groups or halogen-substituted alkyl means.
  • radicals, radicals or compounds modified with the expression “lower” contain, unless stated otherwise, up to 7, primarily up to 4 carbon atoms.
  • Alkyl is especially lower alkyl, e.g. B. isopropyl, straight-chain or branched, butyl, pentyl, hexyl or heptyl bound in any position and especially methyl, ethyl or n-propyl.
  • Possible substituents of the optionally substituted alkyl group are primarily free or etherified hydroxy groups, e.g. B. lower alkoxy groups, or halogen atoms.
  • the substituted alkyl radical such as lower alkyl radical, can carry one, two or more identical or different substituents, in particular free hydroxyl groups or halogen atoms.
  • Aralkyl is, in particular, aryl-lower alkyl, the lower alkyl part above all corresponding to the above-mentioned lower alkyl, and being primarily methyl or ethyl.
  • the aromatic part is in particular a monocyclic and bicyclic aryl radical, primarily phenyl, but also naphthyl. He can optionally, for. B. by lower alkyl groups, free or etherified hydroxy, for. B. lower alkoxy or lower alkylenedioxy, halogen atoms and / or trifluoromethyl be mono-, di- or poly-substituted. Particularly noteworthy are 2-phenylethyl, chlorobenzyl, methylbenzyl, hydroxybenzyl, methoxybenzyl or especially benzyl.
  • the alkylidene radical is, in particular, a lower alkylidene radical, such as the 2-butylidene, 3-pentylidene and primarily isopropylidene radical.
  • the cycloalkylidene radical preferably contains 5-7 ring carbon atoms and is primarily cyclopentylidene or cyclohexylidene.
  • Acyl is in particular an acyl residue of an organic acid, in particular an organic carboxylic acid.
  • Acyl is especially alkanoyl, especially with 2-18 carbon atoms, such as acetyl or propionyl, or also aroyl, such as naphthoyl-1, naphthoyl-2 and especially benzoyl or benzoyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy or lower alkanoyloxy or naphthoyl.
  • Acyl can also be an acyl residue of an organic sulfonic acid, e.g. B.
  • an alkanesulfonic acid especially a lower alkanesulfonic acid, such as methanesulfonic acid or ethanesulfonic acid, or an arylsulfonic acid, especially an optionally lower alkyl-substituted phenylsulfonic acid, such as benzenesulfonic acid or p-toluenesulfonic acid, and the rest of a carbamic acid, such as unsubstituted carbamoyl, lower alkyl-carbamoyl or aryl- carbamoyl, such as methylcarbamoyl or phenylcarbamoyl.
  • Lower alkyl as a substituent of the abovementioned radicals, is primarily methyl or ethyl, but also n-propyl, isopropyl or straight-chain or branched butyl.
  • Lower alkoxy as a substituent of the abovementioned radicals, is in particular methoxy or ethoxy, furthermore n-propoxy, isopropoxy, n-butoxy or isobutoxy.
  • Halogen is e.g. B. fluorine, chlorine or bromine.
  • the new compounds can be in the form of mixtures of anomers or of pure a- or ⁇ -anomers.
  • the new compounds have valuable pharmacological properties, in particular they have a very good effect in some different types of transplantable tumors and leukemias, as well as in part in virus-induced leukemia.
  • doses of 25-500 mg / kg i.p. a strong inhibition of tumor growth in mice with z. B. Ehrlich ascites carcinoma or solid Harding-Passey melanoma, and in rats with z. B. Yoshida Ascites Sarcom.
  • Analog doses prolong life compared to controls in mice with e.g. B. Leukemia L 1210 or Rauscher leukemia.
  • the compounds according to the invention show a broad spectrum of activity not only against transplantable ascitic tumors (CrSa 180, Ehrlich carcinoma), but above all also against various solid, transplantable or chemically induced tumors.
  • the invention relates in particular to compounds of the formula I in which R and R 2 are hydrogen, lower alkyl optionally substituted by hydroxyl, lower alkoxy or halogen, optionally substituted by hydroxy, lower alkoxy, halogen or trifluoromethyl, primarily in the para position, substituted benzyl, R, and R 2 also denotes lower alkylidene or cycloalkylidene with 5-6 carbon atoms, R 3 and R 5 optionally lower alkyl substituted by hydroxy, lower alkoxy or halogen, optionally substituted by hydroxy, lower alkoxy, halogen or trifluoromethyl, primarily in the p-position, substituted benzyl, or lower alkanoyl, e.g. B.
  • acetyl or propionyl or optionally substituted by halogen, lower alkoxy, hydroxy or lower alkanoyloxy benzoyl, e.g. B. p-chlorobenzoyl, p-bromobenzoyl, p-methoxybenzoyl or o- or p-hydroxybenzoyl, but together also mean lower alkylidene or cycloalkylidene having 5-6 carbon atoms and R 6 is lower alkyl optionally substituted by halogen, hydroxy or lower alkoxy.
  • R, lower alkyl and R 2 are hydrogen or R, and R 2 together are lower alkylidene
  • R 3 and R 5 are lower alkyl or optionally substituted by halogen, hydroxy, lower alkoxy or alkyl, especially in the p-position
  • Benzyl or R 6 optionally substituted with chlorine lower alkyl, e.g. B. represent methyl or chloroethyl.
  • R 3 and R 5 are methyl
  • R 6 is methyl or chloroethyl and R
  • hydrogen, methyl, ethyl or propyl and R 2 is hydrogen or R
  • R 2 together is the isopropylidene radical.
  • the new compounds are obtained if a compound of the formula II nitrosated in a manner known per se.
  • compound II is preferably reacted with nitrous acid, its salts or derivatives.
  • a salt such as an alkali or alkaline earth metal, in particular the sodium salt of nitrous acid
  • an acid such as a mineral acid, for.
  • hydrochloric acid, sulfuric acid or nitric acid an organic acid such as carbonic acid, acetic acid or a sulfonic acid, e.g. B. a lower alkanesulfonic acid, such as methane or ethanesulfonic acid or a sulfonic acid group containing ion exchanger, for.
  • B. Amberlite IR 120 the nitrous acid free. But you can also an anhydride of nitrous acid, especially a mixed anhydride with z.
  • As the nitric acid or a hydrohalic acid use.
  • reaction is preferably carried out at low temperature, e.g. B. -10 ° C to 30 ° C.
  • the starting materials used in this process method are new. They can be obtained in a manner known per se from a corresponding glucofuranose which is unsubstituted in the 6-position, e.g. B. by converting to a reactive ester, e.g. B. with an alkanesulfonic acid, arylsulfonic acid or hydrohalic acid, then to an azide and reduction of the azide thus obtained to 6-deoxy-6-amino-glucofuranose, which then with a suitable NR 6 -carbamic acid derivative, such as a corresponding isocyanate for 6- Deoxy-6 - (- 3-R 6 -ureido) -glucofuranose is condensed. As mentioned above, these reactions are carried out in a manner known per se.
  • Another method for the preparation of the new nitrosoureas consists in that a compound of formula III with a reactive derivative of an N-nitroso-NR s -carbamic acid (IV) implements.
  • the reactive derivative can be, for example, an acid anhydride, preferably a mixed acid anhydride, such as an acid azide or an activated ester.
  • Activated esters include, in particular, cyanomethyl esters, carboxymethyl esters, paranitrophenyl thioesters, paranitrophenyl esters, 2,4,5-trichlorophenyl esters, pentachlorophenyl esters, N-hydroxy-succinimide esters, N-hydroxy-phalimide esters, 8-hydroxyquinoline esters or N-hydroxypiperidine esters.
  • This reaction is carried out in a manner known per se, preferably in a solvent such as water or a halogenated coal water serstoff, e.g. B. dichloro- or trichloroethane, an ether such as diethyl ether, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, or an optionally alkylated pyridine, such as pyridine, picoline, lutidine, or quinoline.
  • a solvent such as water or a halogenated coal water serstoff, e.g. B. dichloro- or trichloroethane, an ether such as diethyl ether, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, or an optionally alkylated pyridine, such as pyridine, picoline, lutidine, or quinoline.
  • the starting materials used are known or can be prepared in a manner known per se. So you can the amine of formula 111 from a corresponding, in the 6-position unsubstituted glucofuranose, for. B. by converting to a reactive ester, e.g. B. with an alkane or arylsulfonic acid or a hydrohalic acid, and then to an azide and reduction of the azide thus obtained to 6-deoxy-6-amino-glucofuranose.
  • a reactive ester e.g. B. with an alkane or arylsulfonic acid or a hydrohalic acid
  • the new compounds can be present as pure ⁇ or ⁇ anomers or as anomer mixtures.
  • the latter can be separated into the two pure anomers in a known manner due to the physicochemical differences or constituents, e.g. By means of chromatographic separation, such as thin layer chromatography or any other suitable separation method.
  • chromatographic separation such as thin layer chromatography or any other suitable separation method.
  • the more effective of the two anomers is preferably isolated.
  • the invention also relates to those embodiments of the process in which a starting material is formed under the reaction conditions or used in the form of a reactive derivative or salt.
  • the starting materials used are preferably those which, according to the process, lead to the compounds described above as being particularly valuable.
  • the present invention also relates to pharmaceutical preparations which contain compounds of the formula.
  • the pharmaceutical preparations according to the invention are those for enteral, such as oral and rectal and parenteral administration to warm-blooded animals, which contain the pharmacological active ingredient alone or together with a pharmaceutically usable carrier material.
  • the dosage of the active ingredient depends on the warm-blooded species, the age and the individual condition as well as on the mode of administration.
  • the new pharmaceutical preparations contain from about 10% to about 95%, preferably from about 20% to about 90% of the active ingredient.
  • Pharmaceutical preparations according to the invention can e.g. B. present in unit dosage forms such as coated tablets, tablets, capsules, suppositories or ampoules.
  • the pharmaceutical preparations of the present invention are manufactured in a manner known per se, e.g. B. produced by means of conventional mixing, granulating, coating, solution or lyophilization processes.
  • Suitable carriers are in particular fillers such as sugar, e.g. B. lactose, sucrose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates, e.g. As tricalcium phosphate or calcium hydrogen phosphate, further binders, such as starch paste using z. B.
  • fillers such as sugar, e.g. B. lactose, sucrose, mannitol or sorbitol, cellulose preparations and / or calcium phosphates, e.g. As tricalcium phosphate or calcium hydrogen phosphate, further binders, such as starch paste using z. B.
  • ком ⁇ онентs such as the above-mentioned starches, furthermore carboxymethyl starch, cross-linked polyvinyl pyrrolidone, agar, Alginic acid or a salt thereof, such as sodium alginate, auxiliaries are primarily flow regulators and lubricants, e.g. B. silica, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and / or polyethylene glycol.
  • flow regulators and lubricants e.g. B. silica, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and / or polyethylene glycol.
  • Dragee kernels are provided with suitable, optionally gastric juice-resistant coatings, u. a. Concentrated sugar solutions, which optionally contain arabic gum, talc, polyvinylpyrrolidone, polyethylene glycol and / or titanium dioxide, lacquer solutions in suitable organic solvents or solvent mixtures or, for the production of gastric juice-resistant coatings, solutions of suitable cellulose preparations, such as acetyl cellulose phthalate or hydroxypropylmethyl cellulose phthalate.
  • the tablets or dragee coatings can contain dyes or pigments, e.g. B. for identification or labeling of different doses of active ingredient.
  • the daily dose for a warm-blooded animal weighing approximately 70 kg is approximately 10-500 mg per day, preferably 50-300 mg per day .
  • the residue is purified by column chromatography on silica gel with methylene chloride / ethyl acetate (85:15), the crystalline product is combined with the first crystals and recrystallized from ether / petroleum ether.
  • the corresponding ⁇ -glucofuranoside shows the Rf value 0.11 in the same system.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP78100115A 1977-06-15 1978-06-07 Glucofuranosid-6-yl-Nitrosoharnstoffderivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel Expired EP0000126B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KE356085A KE3560A (en) 1977-06-15 1985-09-12 Glucofuranos-6-yl-nitroso prea derivatives,process for their preparation and pharmaceuticals containing them

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH7359/77 1977-06-15
CH735977 1977-06-15

Publications (2)

Publication Number Publication Date
EP0000126A1 EP0000126A1 (de) 1979-01-10
EP0000126B1 true EP0000126B1 (de) 1982-12-01

Family

ID=4323894

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100115A Expired EP0000126B1 (de) 1977-06-15 1978-06-07 Glucofuranosid-6-yl-Nitrosoharnstoffderivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel

Country Status (27)

Country Link
US (1) US4273766A (fi)
EP (1) EP0000126B1 (fi)
JP (1) JPS545909A (fi)
AR (2) AR221845A1 (fi)
AT (1) AT358601B (fi)
AU (1) AU517665B2 (fi)
CA (1) CA1096859A (fi)
CS (1) CS203193B2 (fi)
CY (1) CY1263A (fi)
DD (1) DD137360A5 (fi)
DE (1) DE2862098D1 (fi)
DK (1) DK267078A (fi)
ES (1) ES470738A1 (fi)
FI (1) FI65781C (fi)
GR (1) GR73054B (fi)
HK (1) HK2285A (fi)
HU (1) HU179686B (fi)
IE (1) IE47090B1 (fi)
IL (1) IL54909A (fi)
MY (1) MY8700029A (fi)
NO (1) NO145843C (fi)
NZ (1) NZ187571A (fi)
PL (2) PL112747B1 (fi)
PT (1) PT68164A (fi)
SG (1) SG44284G (fi)
SU (2) SU910118A3 (fi)
ZA (1) ZA783430B (fi)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CY1264A (en) * 1978-02-21 1984-11-23 Ciba Geigy Ag Glycofuranosyl-nitrosourea derivatives,process for their manufacture and their pharmaceutical preparations
FR2487343A1 (fr) * 1980-07-25 1982-01-29 Anvar Nouveaux nitroso-carbamates, procede pour leur preparation et application a la synthese selective de n-nitrosourees
JPS57165398A (en) * 1981-04-02 1982-10-12 Tanabe Seiyaku Co Ltd Nitrosourea derivative and its preparation
JPS57200397A (en) * 1981-06-03 1982-12-08 Akira Kimura Novel aldohexopyranose-, aldopentopyranose-, or and medicament composition comprising it aldopentofuranose- nitrosourea compound, its preparation
US4902791A (en) * 1983-08-30 1990-02-20 Sanofi S.A. Nitrosourea derivatives, process for their preparation and medicaments containing them
US4613590A (en) * 1985-08-19 1986-09-23 Abbott Laboratories Amino D-manno-2-octulopyranosidonate containing compounds, pharmaceutical compositions and method of use
FR2614304A1 (fr) * 1987-04-22 1988-10-28 Sanofi Sa Derives de nitrosourees, leur nouveau procede de preparation et leurs applications therapeutiques.
ATE238804T1 (de) * 1993-06-11 2003-05-15 Boston Life Sciences Inc Immunomodulierende, entzündungshemmende und antiproliferative verbindungen:5,6-dideoxy, 5- aminoderivate von idose und 6-deoxy, 6- aminoderivate von glukose
DE602005026361D1 (de) * 2004-12-17 2011-03-31 Kao Corp Make-up Zubereitung

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5230491B2 (fi) * 1974-07-05 1977-08-09
JPS5126819A (en) * 1974-08-08 1976-03-05 Tokyo Tanabe Co Arukiru nn karubamiru n**22 kuroruechiru n** nitoroso dd gurukopiranoshidojudotaino seizoho
JPS5126876A (en) * 1974-08-08 1976-03-05 Suami T Shinkina nitorosonyosojudotaino seizohoho
US3940383A (en) * 1974-12-12 1976-02-24 Stanford Research Institute Streptozotocin analogs
JPS5175072A (ja) * 1974-12-18 1976-06-29 Tokyo Tanabe Co Ribofuranoozunonitorosokarubamirujudotaino seizoho

Also Published As

Publication number Publication date
HU179686B (en) 1982-11-29
MY8700029A (en) 1987-12-31
FI781779A7 (fi) 1978-12-16
SG44284G (en) 1985-03-29
FI65781B (fi) 1984-03-30
ES470738A1 (es) 1979-01-16
IL54909A (en) 1981-09-13
US4273766A (en) 1981-06-16
FI65781C (fi) 1984-07-10
DD137360A5 (de) 1979-08-29
CS203193B2 (en) 1981-02-27
ATA433378A (de) 1980-02-15
PL113378B1 (en) 1980-12-31
GR73054B (fi) 1984-01-26
AU3708978A (en) 1979-12-20
SU910118A3 (ru) 1982-02-28
AR221845A1 (es) 1981-03-31
SU917699A3 (ru) 1982-03-30
AU517665B2 (en) 1981-08-20
IE47090B1 (en) 1983-12-14
NZ187571A (en) 1980-10-08
DK267078A (da) 1978-12-16
PL207625A1 (pl) 1979-06-04
PL112747B1 (en) 1980-10-31
HK2285A (en) 1985-01-18
AR222844A1 (es) 1981-06-30
ZA783430B (en) 1979-06-27
JPS545909A (en) 1979-01-17
CY1263A (en) 1984-11-23
IE781193L (en) 1978-12-15
NO145843C (no) 1982-06-09
CA1096859A (en) 1981-03-03
PT68164A (en) 1978-07-01
EP0000126A1 (de) 1979-01-10
AT358601B (de) 1980-09-25
DE2862098D1 (en) 1983-01-05
NO145843B (no) 1982-03-01
NO782069L (no) 1978-12-18

Similar Documents

Publication Publication Date Title
DE2655500A1 (de) Glucosaminderivate und ein verfahren zu deren herstellung
EP0000126B1 (de) Glucofuranosid-6-yl-Nitrosoharnstoffderivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel
US4145414A (en) Organic compounds and compositions of ara-cytidine
CH504457A (de) Verfahren zur Herstellung neuer antibiotisch wirksamer Kondensationsprodukte von Rifamycin S
US3531462A (en) Carbonates of cardenolide tridigitoxosides and ester derivatives thereof
EP0000741B1 (de) Indolacetoxyacetylaminosäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimittel
DE3413489C2 (fi)
EP0003788B1 (de) Glucofuranosyl-nitrosoharnstoffderivate, Verfahren zu deren Herstellung und ihre pharmazeutischen Präparate
EP0314011A2 (de) Purinderivate
EP0292023A2 (de) Pyrimidinderivate
CH642668A5 (de) 2,6-diaminonebularine, verfahren zu deren herstellung und sie enthaltende pharmazeutische praeparate.
CH636626A5 (de) Nitroso-harnstoffverbindungen und verfahren zu ihrer herstellung und verwendung derselben in therapeutischen mitteln.
DE1793336C3 (de) D-Glucofuranoside, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Präparate
EP0085275A1 (de) Substituierte Thiazolidinylester von Mineralsäuren
EP0064635A1 (de) Aminocyclitderivate, ihre Herstellung und sie enthaltende Arzneimittel
DE68928127T2 (de) 2'-Methylidenpyrimidinnukleosidverbindungen, ihre Verwendung und Verfahren zu ihrer Herstellung
DE1804983A1 (de) Verfahren zur Herstellung von Cephalosporansaeurederivaten
EP0349928A2 (de) Purinderivate
DE60004362T2 (de) Thiazolopyrimidine verwendbar als TNF-Alpha Inhibitoren
DE69012845T2 (de) Exo-3'-4'-O-benzyliden-3"-demethylchartreusin und seine Salze.
DE69314947T2 (de) 2-aminozuckermakrolid-derivate
EP0324390A2 (de) Nigericinderivate, Verfahren zu deren Herstellung, diese enthaltende Mittel und Verwendung derselben sowie die Verwendung von Nigericin als antiviral wirksame Substanz
CH629806A5 (en) Process for the preparation of substituted purines
DD142191A5 (de) Verfahren zur herstellung von n tief 1-glucofuranosid-6-yl-n tief 3-nitrosoharnstoffen
EP0484660A1 (de) Neue 5-(Phenoxyalkanoylamino)-uracile, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): BE CH DE FR GB NL SE

17P Request for examination filed
GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): BE CH DE FR GB NL SE

Designated state(s): BE CH DE FR GB NL SE

REF Corresponds to:

Ref document number: 2862098

Country of ref document: DE

Date of ref document: 19830105

ET Fr: translation filed
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19840521

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19840601

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 19840630

Year of fee payment: 7

Ref country code: BE

Payment date: 19840630

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19840727

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 19870630

Year of fee payment: 10

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Effective date: 19890607

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Effective date: 19890608

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Effective date: 19890630

Ref country code: BE

Effective date: 19890630

BERE Be: lapsed

Owner name: CIBA-GEIGY A.G.

Effective date: 19890630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Effective date: 19900101

GBPC Gb: european patent ceased through non-payment of renewal fee
NLV4 Nl: lapsed or anulled due to non-payment of the annual fee
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19900228

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19900301

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

EUG Se: european patent has lapsed

Ref document number: 78100115.1

Effective date: 19900412

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT