EP0807113A1 - Derives tricycliques et leur utilisation comme agents anticancereux - Google Patents

Derives tricycliques et leur utilisation comme agents anticancereux

Info

Publication number
EP0807113A1
EP0807113A1 EP95907087A EP95907087A EP0807113A1 EP 0807113 A1 EP0807113 A1 EP 0807113A1 EP 95907087 A EP95907087 A EP 95907087A EP 95907087 A EP95907087 A EP 95907087A EP 0807113 A1 EP0807113 A1 EP 0807113A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
compound
coor
aryl
indole
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.)
Withdrawn
Application number
EP95907087A
Other languages
German (de)
English (en)
Inventor
David Drysdale Miller
Laddawan Chunchatprasert
Patrick Vivian Richard Shannon
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.)
University College Cardiff Consultants Ltd
Cardiff University
Original Assignee
University College Cardiff Consultants Ltd
Cardiff University
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 University College Cardiff Consultants Ltd, Cardiff University filed Critical University College Cardiff Consultants Ltd
Publication of EP0807113A1 publication Critical patent/EP0807113A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to heterocyclic compounds which have been found to have anti-tumour activity. More specifically, the invention concerns benzo[1,2-b:4,5-b']dipyrroles, benzo[1,2-b:5,4-b' dipyrroles, cyclopent[f]indoles, benzo[1,2-b:4,5-b']difurans, benzo[1,2-b:5,4-b']difurans, 2H-indeno[5,6-b]furans, benzo[1,2-b:4,5-b']dithiophenes, benzo[1,2-b:5,4-b']dithiophenes, cyclopent[f]indenes and 5H-furo[2,3-f]indoles methods for their preparation, pharmaceutical formulations containing them and their use as anti-tumour agents.
  • anti-tumour agents which have differing degrees of efficacy.
  • Standard clinically used agents include adriamycin, actinomycin D, methotrexate, 5-fluorouracil, cis-platinum, vincristine and vinblastine.
  • these presently available anti-tumour agents are known to have various disadvantages, such as toxicity to healthy cells and resistance to certain tumour types.
  • novel compounds which exhibit anti-tumour cell activity including a group of novel compounds which exhibit anti-tumour cell activity with low toxicity against normal cell lines.
  • the present invention provides a compound of the general formula (1)
  • X is O, S, SO, SO 2 , CH 2 , CO or NR 7 , wherein R 7 is H, alkyl, aralkyl, aryl, alkenyl, acyl, alkynyl, sulphonyl, substituted sulphonyl, or COOMe;
  • Y is O, S, SO, SO 2 , CH 2 , CO or NR 7 ;
  • R 1 is COR 8 , CHO, CH 2 OH, CH 2 OR 8 , CONH 2 , COOR 8 , CONHR 8 , CONR 8 R 9 , CSOR 8 , CSSR 8 , COSR 8 , CSNHR 8 , CSNR 8 R 9 , CNHOR 8 wherein R 8 and R 9 are independently hydrogen, alkoxyalkyl, heterocycloalkyl, heteroaralkyl, or C 1-10 optionally substituted hydrocarbyl group which may optionally contain one or two oxygen atoms in the chain; or R 8 and R 9 are a sugar group.
  • R 2 is H, halo, cyano, COOR 8 , alkyl, aryl, alkenyl, alkynyl, alkoxy, (wherein alkyl, aryl, alkenyl, alkynyl and alkoxy can be substituted) or CH 2 CH 2 CO 2 R 12 wherein R 12 is alkyl or aryl;
  • R 3 is H, alkyl, halogen, cyano, amino, COOR 8 , CONHR 8 , COR 8 , CH 2 OH, CH 2 OR 8 , CONH 2 , CONR 8 R 9 , CSOR 8 , CSSR 8 , COSR 8 , CSNHR 8 , CSNR 8 R 9 or CNHOR 8 ;
  • R 4 is H, halogen, cyano, amino, alkyl, COOR 8 , CONHR 8 , COR 8 , CH 2 OH, CH 2 OR 8 , CONH 2 , CONR 8 R 9 , CSOR 8 , CSSR 8 , COSR 8 , CSNHR 8 , CSNR 8 R 9 or CNHOR 8 ;
  • R 5 is H, hydroxy, aryloxy, aralkyloxy, alkyl, substituted alkyl, aralkyl, nitro, amino, halo, cyano COOR 8 or CHO;
  • R 6 is H, aryl, alkyl, aralkyl, nitro, halogen, CHO or COR 13 wherein R 13 is alkyl or aryl; wherein R 8 is not H when R 2 is H and R 3 is not H or Me when A is
  • Alkyl groups present in general formula (I) may be straight or branched chain alkyl groups, and may contain 1-10 carbon atoms and suitably 1-6 carbon atoms. Examples of such alkyl groups include methyl, ethyl, t-butyl and the like.
  • Acyl groups may be straight or branched and may contain 1-10 carbon atoms and suitably 1-6 carbon atoms. Examples of suitable acyl groups include ethanoyl and propanoyl groups.
  • Alkoxy may be straight or branched and may contain 1-10 carbon atoms and suitably 1-6 carbon atoms. Examples of suitable alkoxy groups include methoxy, ethoxy and the like.
  • Aryl includes both carbocyclic aryl groups and heterocyclic aryl groups normally containing a maximum of 10 ring atoms.
  • Carbocyclic aryl groups include, eg phenyl and naphthyl and contain at least one aromatic ring.
  • Heterocyclic aryl groups include eg thienyl, furyl, pyridyl, indole and guinoline rings.
  • An aralkyl group may contain from 1 to 4 atoms in the alkyl portion and the aryl portion may be a carbocyclic or heterocyclic aryl group.
  • Cycloalkyl includes both cycloalkyl groups and heterocyclo alkyl groups normally containing between 3 and 6 ring atoms.
  • Heterocycloalkyl groups include e.g. raorpholino, thiomorpholino, piperidino, imidazolino, pyrrolidino, pyrazolidino, piperazino, tetrahydrofuranyl, tetrahydropyranyl.
  • R 8 and R 9 are independently optionally substituted C 1-10 hydrocarbyl which may optionally contain one or two oxygen atoms in the chain this includes optionally substituted alkyl, hydroxyalkyl, alkenyl, alkynyl, carbamoylalkyl, alkoxyalkyl, cycloalkyl, cycloalkenyl, aralkyl, aryloxyalkyl.
  • Substituents which may be present on the C 1-10 hydrocarbyl group which may optionally contain one or two oxygen atoms in the chain include hydroxy, azido, alkenyl, halo, nitro (NO 2 ), amino, (optionally substituted by one or 2 alkyl groups), cyano, carboxylate, alkyl ester, aralkyl esters or aryl esters, (wherein the alkyl ester, aralkyl ester and aryl ester can be substituted) alkyl, aryl, aralkyl, aryloxy, arylalkoxy, substituted arylalkoxy, sulphinyl, sulphonyl, thio, alkylthio, alkoxy, hydroxyalkyl, halo alkyl, phosphate, phosphonate, silyl, silyloxy, (wherein silyl and silyloxy may be substituted by one or more C 1-6 alkyl or aryl
  • R 8 is a sugar this group may be present in a protected or unprotected form.
  • Preferred sugar-protecting groups include isopropylidene, benzylidene acetate, benzoyl, paranitrobenzyl, paranitrobenzoyl, benzyl, substituted silyl and tetrahydropyranyl.
  • R 8 is a sugar such as a tetrose, pentose, hexose (including furanose and pyranose) or heptose
  • preferred sugars include glucose, fructose, mannose, ribose, arabinose.
  • Substituents which may be present on the sulphonyl and sulphinyl include alkyl, aryl and aralkyl.
  • Halogen represents fluoro, chloro, bromo or iodo.
  • X preferably represents NH, A is preferably
  • Y preferably represents NH.
  • R 1 is preferably COOR 8 , with R 8 preferably being alkyl or aralkyl.
  • R 2 is preferably H, alkyl, or COOR 8 wherein R 8 is preferably alkyl
  • R 3 is preferably alkyl
  • R 1 is preferably alkyl or COOR 8 .
  • R 5 is preferably hydrogen and
  • R 6 is preferably hydrogen or methyl and salts and physiologically functional derivatives thereof.
  • One group of preferred compounds according to the present invention includes: Ethyl 1,7-dihydro-3,4,6-trimethylpyrrolo[3,2-f]indole-2-carboxylate;
  • a second group of preferred compounds according to the invention include:
  • the present invention also provides a process for preparing compounds of general formula (I), which process comprises the catalysed reaction of a compound of formula (II) with a compound of formula (III) in an inert solvent at a temperature between room temperature and the reflux temperature of the solvent, wherein X, Y, R 1 , R 2 , R 3 R 4 , R 5 and R 6 are as defined herein except that R 3 and R 4 may not be hydrogen when X is NH, and L is a leaving group:-
  • Preferred catalysts are Montmorillonite K 10 clay or p-toluenesulphonic acid.
  • Preferred solvents are 1,2-dichloroethane or toluene. Examples of suitable leaving groups include -OCOCH 3 , OEt, -N + Me 3 and halo.
  • the appropriate aromatic polyheterocycle can be reacted with a formylating agent, such as that generated by the reaction between SnCl, and Cl 2 CHOCH 3 or equivalent reagents.
  • a formylating agent such as that generated by the reaction between SnCl, and Cl 2 CHOCH 3 or equivalent reagents.
  • Suitable functional groups include CHBr 2 , CH 3 , COR 14 wherein R 14 is a primary or secondary C 1-6 alkyl group, COOH or a derivative thereof such as an ester, amide, acid chloride or CN; or
  • the compounds of the present invention are useful for the treatment of tumours. They may be employed in treating various forms of cancer of mammals including carcinomas, for instance of the stomach, pancreas, breast, uterus and colon; adenocarcinomas, for instance of the lung and colon; sarcomas, for instance fibrosarcoma; leukaemias, for instance lymphocytic leukaemia and lymphomas, for instance myeloid lymphoma.
  • the invention thus further provides a method for the treatment of tumours in animals, including mammals, especially humans, which comprises the administration of a clinically useful amount of compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative in a pharmaceutically useful form, once or several times a day or in any other appropriate schedule, orally, rectally, parenterally, or applied topically.
  • a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for use in therapy for example as an antitumour agent.
  • the amount of compound of formula (I) required to be effective against the aforementioned tumours will, of course, vary and is ultimately at the discretion of the medical or veterinary practitioner.
  • the factors to be considered include the condition being treated, the route of administration, and nature of the formulation, the mammal's body weight, surface area, age and general condition, and the particular compound to be administered.
  • a suitable effective anti-tumour dose is in the range of about 0.01 to about 100 mg/kg body weight, eg 0.1 to about 100 mg/kg body weight, preferably 1-30 mg/kg body weight.
  • the total daily dose may be given as a single dose, multiple doses, e.g., two to six times per day or by intravenous infusion for selected duration.
  • the dose range would be about 8 to 900 mg per day, and a typical dose could be about 50 mg per day. If discrete multiple doses are indicated treatment might typically be 15 mg of a compound of formula (I) given up to 4 times per day.
  • Formulations of the present invention for medical use, comprise a compound of formula (I) or a salt thereof together with one or more pharmaceutically acceptable carriers and optionally other therapeutic ingredients.
  • the carrier(s) should be pharmaceutically acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
  • the present invention therefore, further provides a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof together with a pharmaceutically acceptable carrier thereof.
  • a method for the preparation of a pharmaceutical formulation comprising bringing into association a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof, and a pharmaceutically acceptable carrier thereof.
  • Formulations according to the present invention include those suitable for oral, topical, rectal or parenteral (including subcutaneous, intramuscular and intravenous) administration.
  • Preferred formulations are those suitable for oral or parenteral administration.
  • the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active compound into association with a carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing the active compound into association with a liquid carrier or a finely divided solid carrier or both and then, if necessary, shaping the product into desired formulations.
  • Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets, tablets or lozenges, each containing a predetermined amount of the active compound; as a powder or granules; or a solution or suspension in an aqueous or non-aqueous liquid such as a syrup, an elixir, an emulsion or a draught.
  • a tablet may be made by compression or moulding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active compound in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent.
  • Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered active compound with any suitable carrier.
  • a syrup may be made by adding the active compound to a concentrated, aqueous solution of a sugar, for example sucrose, to which may also be added any accessory ingredients.
  • a sugar for example sucrose
  • accessory ingredients(s) may include flavourings, an agent to retard crystallisation of the sugar or an agent to increase the solubility of any other ingredients, such as a polyhydric alcohol for example glycerol or sorbitol.
  • Formulations for rectal administration may be presented as a suppository with a conventional carrier such as cocoa butter.
  • Formulations suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active compound which is preferably isotonic with the blood of the recipient.
  • Such formulations suitably comprise a solution of a pharmaceutically and pharmacologically acceptable acid addition salt of a compound of the formula (I) that is isotonic with the blood of the recipient.
  • Useful formulations also comprise concentrated solutions or solids containing the compound of formula (I) which upon dilution with an appropriate solvent give a solution for parenteral administration as above.
  • the formulations of this invention may further include one or more accessory ingredient(s) selected from diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives (including antioxidants) and the like.
  • the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for the manufacture of a medicament for the treatment of tumours.
  • IR spectra were recorded on a Perkin-Elmer 257 grating spectrophotometer or a Bruker FS66 spectrophotometer.
  • Example 2 The general procedure of Example 1 was followed using ethyl 5-acetoxymethyl-4-acetyl-3-methylpyrrolo-2 carboxylate (0.692g, 2.59mmol), 3-methoxycarbonyl-2-methylpyrrole (0.360g, 2.59mmol), 1,2-dichloroethane (25 cm 3 ) and Montmorillonite clay (2g). Chromatographic separation using (0-20%) ethyl acetate in dichloromethane gave ethyl 1,7-dihydro-3,4,6-trimethylpyrrolo[3,2-f]indole-2-carboxylate as a pale yellow solid (0.0124g, 1.8%) m.p.
  • Toluene-p-sulfonic acid (100 mg) was added to the solution of the 3-acetyl-5-ethoxycarbonyl-2-(1'-methoxy-carbonylpyrrol-2'-ylmethyl)-4-methlypyrrole (0.435 g, 1.31 mmol) in benzene (50 cm 3 ), the reaction mixture was heated under reflux for 5h (using Dean-Stark apparatus).
  • Assays for cell proliferation/cytotoxity were carried out in tissue culture grade 96 well microtitre plates (Costar). Cells in log growth were added to the plates at a concentration of 1 ⁇ 10 3 cells per well on day 0 and serially diluted compounds were then added on day 1. Plates were then incubated at 37°C in 5% CO 2 in air for a further 4 days.
  • the methylene blue biomass staining method was used, the test being read on a Multiscan plate reader at wavelength of 620nm.
  • the morphology of the cells was checked microscopically under phase-contrast immediately before the fixation and staining with methylene blue, and by ordinary light microscopy thereafter.
  • IC50 values for active compounds were obtained using the computer programme, GS1 and dose-response slopes were also plotted.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composé de la formule (I), ou sel ou dérivé physiologiquement fonctionnel de ce composé; formule dans laquelle A représente (a), (b), (c) ou (d), X représente O, S, SO, SO2, CH2, CO ou NR7, R7 représentant H, alkyle, aralkyle, aryle, alcényle, acyle, alcynyle, sulfonyle, sulfonyle substitué ou COOMe; Y représente O, S, SO, SO¿2?, CH2, CO ou NR?7; R1¿ représente COR8, CHO, CH¿2?OH, CH2OR?9¿, CONH¿2?, COOR?8, CONHR8, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9, CNHOR8, R8 et R9¿ représentant indépendamment hydrogène, alcoxyalkyle, hétérocycloalkyle, hétéroaralkyle, ou un groupe C¿1-10? hydrocarbyle éventuellement substitué qui peut éventuellement contenir un ou deux atomes d'oxygène dans la chaîne; ou R?8 et R9¿ représentent un groupe de sucre. R2 représente H, halo, cyano, COOR8, alkyle, aryle, alcényle, alcynyle, alcoxy (alkyle, aryle, alcényle, alcynyle et alcoxy pouvant être substitués) ou CH¿2?CH2CO2R?12, où R12¿ représente alkyle ou aryle; R3 représente H, alkyle, halogène, cyano, amino, COOR?8, CONHR8, COR8, CH¿2OH, CH2OR8, CONH¿2?, CONR?8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9¿ ou CNHOR8; R4 représente H, halogène, cyano, amino, alkyle, COOR?8, CONHR8, COR8, CH¿2OH, CH2OR8, CONH¿2?, CONR?8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9¿ ou CNHOR8; R5 représente H, hydroxy, aryloxy, aralkyloxy, alkyle, alkyle substitué, aralkyle, nitro, amino, halo, cyano COOR8 ou CHO; R6 représente H, aryle, alkyle, aralkyle, nitro, halogène, CHO ou COR?13, où R13¿ représente alkyle ou aryle; R8 ne représente pas H lorsque R2 représente H, et R3 ne représente pas H ou Me lorsque A représente (c). Des procédés de préparation de ces composés sont également décrits, ainsi que leur utilisation dans le domaine médical, en particulier pour la thérapie anticancéreuse, et des formulations pharmaceutiques les comprenant.
EP95907087A 1994-02-02 1995-02-01 Derives tricycliques et leur utilisation comme agents anticancereux Withdrawn EP0807113A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9401994 1994-02-02
GB9401994A GB9401994D0 (en) 1994-02-02 1994-02-02 Heterocyclic compounds
PCT/GB1995/000203 WO1995021171A1 (fr) 1994-02-02 1995-02-01 Derives tricycliques et leur utilisation comme agents anticancereux

Publications (1)

Publication Number Publication Date
EP0807113A1 true EP0807113A1 (fr) 1997-11-19

Family

ID=10749741

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95907087A Withdrawn EP0807113A1 (fr) 1994-02-02 1995-02-01 Derives tricycliques et leur utilisation comme agents anticancereux

Country Status (3)

Country Link
EP (1) EP0807113A1 (fr)
GB (1) GB9401994D0 (fr)
WO (1) WO1995021171A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9804343D0 (en) * 1998-02-27 1998-04-22 Univ Cardiff Chemical compounds
GB0302094D0 (en) 2003-01-29 2003-02-26 Pharmagene Lab Ltd EP4 receptor antagonists
GB0324269D0 (en) 2003-10-16 2003-11-19 Pharmagene Lab Ltd EP4 receptor antagonists

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5248692A (en) * 1990-06-11 1993-09-28 Kyowa Hakko Kogyo Co., Ltd. DC-89 derivatives as anti-tumor agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9521171A1 *

Also Published As

Publication number Publication date
GB9401994D0 (en) 1994-03-30
WO1995021171A1 (fr) 1995-08-10

Similar Documents

Publication Publication Date Title
JP3528968B2 (ja) 三環式複素環誘導体化合物およびその化合物を有効成分とする医薬
EP1390371A1 (fr) Oxazolopyrimidines et furopyrimidines et utilisation dans des agents pharmaceutiques contre les tumeurs
DE69823493T2 (de) Tetrahydropyridoverbindungen
CH682151A5 (fr)
JPH01500834A (ja) アザインドール及びインドリジン誘導体、その製造方法及び薬剤としてのその用途
EP0609328B1 (fr) Pyrrolo-pyridazine a effets protecteurs du tube gastro-intestinal
WO1994002483A1 (fr) Composes tetracycliques, procede et intermediaires de preparation, et utilisation comme agents antitumoraux
US6201129B1 (en) Tricyclic derivatives and their use as anti-cancer agents
US4681882A (en) 4-alkoxy-pyrido[2,3-d]pyrimidine derivatives
US5679694A (en) Tetracyclic compounds, intermediates for their preparation and their use as antitumor agents
EP0807113A1 (fr) Derives tricycliques et leur utilisation comme agents anticancereux
IE55900B1 (en) Imidazo(1,2-a)pyrimidines
US4053600A (en) Tricyclic 1,2,4-triazolo-quinazolines
US6013807A (en) Antitumor tetracyclic compounds
EP0222703A1 (fr) Hexahydro-[1]-benzo(pyrano et thiopyrano)-[4,3-c]pyridines
CN101124229A (zh) 用于治疗炎性和过敏性障碍的新杂环化合物
JP3497168B2 (ja) 抗腫瘍活性を有する２−アミノアルキル−５−アミノアルキルアミノ置換イソキノインダゾール−６−（２ｈ）−オン類
CA2211979A1 (fr) Derives tricycliques et leur utilisation comme agents anticancereux
US4547501A (en) Method of using [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives as antidepressant and antifatigue agents
US5264587A (en) Method of preparing α-oxopyrrolo[2,3-b]indole acetic acids and derivatives
PL100184B1 (pl) Sposob wytwarzania nowych pochodnych naftyrydynylo-piroliny
EP0457318A1 (fr) Acides alpha-oxopyrrolo(2,3-b)indole-acétiques, esters, amides et analogues apparentés, un procédé pour leur préparation et leur utilisation comme médicaments
DE3017564A1 (de) Geminale dihalogenderivate kondensierter pyrimidin-4-on-verbindungen, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische kompositionen
JP2006507269A (ja) ピロロ［３，４−ｃ］カルバゾールおよびピリド［２，３−ｂ］ピロロ［３，４−ｅ］インドール誘導体、その製造法、ならびにそれを含有する医薬組成物
CA2502488A1 (fr) Nouveaux derives de [1,4]benzodioxino[2,3-e]isoindole substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

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

17P Request for examination filed

Effective date: 19970813

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT SE

17Q First examination report despatched

Effective date: 19991011

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

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20010410