EP0641311A1 - Nouveaux derives de la dihydroxybenzylamine, leur preparation et les compositions pharmaceutiques qui les contiennent - Google Patents

Nouveaux derives de la dihydroxybenzylamine, leur preparation et les compositions pharmaceutiques qui les contiennent

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Publication number
EP0641311A1
EP0641311A1 EP93910121A EP93910121A EP0641311A1 EP 0641311 A1 EP0641311 A1 EP 0641311A1 EP 93910121 A EP93910121 A EP 93910121A EP 93910121 A EP93910121 A EP 93910121A EP 0641311 A1 EP0641311 A1 EP 0641311A1
Authority
EP
European Patent Office
Prior art keywords
radicals
mmol
equivalent
methanol
yield
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Withdrawn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
EP93910121A
Other languages
German (de)
English (en)
French (fr)
Inventor
Janine Boiziau
Huixiong Résidence Jean-Zay CHEN
Christiane Garbay
Jean-Bernard Le Pecq
Fabienne Parker
Bernard-Pierre Roques
Bruno TOQUE
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.)
Institut National de la Sante et de la Recherche Medicale INSERM
Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
Institut National de la Sante et de la Recherche Medicale INSERM
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 Rhone Poulenc Rorer SA, Institut National de la Sante et de la Recherche Medicale INSERM filed Critical Rhone Poulenc Rorer SA
Publication of EP0641311A1 publication Critical patent/EP0641311A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms

Definitions

  • the present invention relates to new derivatives of 2,5-dihydroxybenzylamine of general formula:
  • Rj or 2 represents a hydrogen or halogen atom, such as a chlorine, bromine or fluorine atom, or a hydroxy, alkoxy, alkylcarbonyloxy radical, arylcarbonyloxy, mercapto, alkylthio, amino, formylamino, alkylcarbonylamino or arylcarbonylamino and the other represents an alkyl, alkoxy, alkoxymethyl, alkylthio, alkylmethyl, alkylcarbonyl, arylcarbonyl, arylcarbonyl, carboxyalkyl nitrogen atom is optionally substituted by one or two radicals, identical or different, chosen from alkyl or phenyl radicals, or thiocarbamoyl, the nitrogen atom of which is optionally substituted by one or two radicals, identical or different, chosen from alkyl or phenyl radicals, it being understood
  • HER2 receptor is amplified in 25 to 30% of these cases and is correlated with a very poor prognosis and a high probability of relapse after resection or treatment [D. Slamon et al., Science, 235. 177-182 (1987)]. These frequently amplified receptors are also found in gastric and / or colon adenocarcinomas. Fukushige et al., Mol. Cell. Biol., Q, 955-958 (1986)]. All of these results tend to confirm that the HER2 receptor is involved in the genesis of certain cancers. T.
  • lavendustine A isolated from the culture of Streptomyces griseolavendus, inhibits the epidermal growth factor receptor (EGF) associated with tyrosine kinase in a system containing an A431 membrane fraction as an enzyme and a tridecapeptide as a substrate at concentrations significantly higher than those obtained with genistein or erbstatin.
  • EGF epidermal growth factor receptor
  • lavendustine A does not show its activity in cell culture tests measuring their growth.
  • Nitric oxide is formed in the brain by stimulation of NMDA (N-methyl-D-aspartate) subtypes of glutamate receptors [Nature, 336. 385-388 (1988)]. This overstimulation of these receptors is associated with a certain number of disease states such as epilepsy, stroke, and netirodegenerative diseases such as senile dementia, Alzheimer's disease or Parkinson's disease [Taylor, Science, 252. 1380-1381 (1991)].
  • NMDA N-methyl-D-aspartate subtypes of glutamate receptors
  • nitric oxide is a messenger of glutamate-induced neurotoxicity and O'Dell et al., Nature, 353. 558-560 (1991) have argued that the enzymes that generate nitric oxide are activated by different kinases including tyrosine kinases.
  • tyrosine kinase inhibitors can inhibit the production of nitric oxide and can be used in the treatment of conditions caused by an increased reactivity of glutamate receptors such as epilepsy, stroke or nerve degeneration.
  • Nitrogen monoxide (NO) can also be a negative regulator of the NMD A receptor. Opposing the production of nitrogen monoxide can have a beneficial effect on NMD A-dependent memorization processes.
  • tyrosine phosphorylation is associated with the cytopathogenic effect of the HIV virus (Science, 256, 542-545 (1992). It follows that the products of general formula (I) may have protective properties against the formation of the HIV virus and the development of the disease.
  • the products according to the invention can act as an inhibitor of the allergic cascade due to the inhibition of cell signaling by basophils and macrophages.
  • the new products of general formula (I) can be obtained by condensation of an aldehyde of formula:
  • the condensation of the aldehyde of formula (II) on the amine of general formula (HT) is carried out by operating in an organic solvent such as an alcohol, such as methanol, or an amide, such as dimethylformamide, or a aromatic hydrocarbon, such as toluene, optionally in the presence of a catalyst such as p.toluenesulfonic acid or boron trifluoride in an ethereal complex or by using a Dean-Stark trap at a temperature between 0 ° C. and the temperature of reflux of the reaction mixture.
  • an organic solvent such as an alcohol, such as methanol, or an amide, such as dimethylformamide, or a aromatic hydrocarbon, such as toluene
  • a catalyst such as p.toluenesulfonic acid or boron trifluoride in an ethereal complex
  • a Dean-Stark trap at a temperature between 0 ° C. and the temperature of reflux of the reaction mixture.
  • a base
  • the reduction of the imine of general formula (IV) to the product of general formula (I) is carried out by means of hydrogen, operating in the presence of a hydrogenation catalyst.
  • a hydrogenation catalyst Palladium on carbon or nickel can advantageously be used as catalysts.
  • the reduction is carried out in an organic solvent such as an alcohol such as methanol, an ester such as ethyl acetate or a halogenated aliphatic hydrocarbon such as dichloromethane at a temperature in the region of 20 ° C.
  • the reduction can optionally be carried out under pressure.
  • the reduction can also be carried out using a borohydride such as sodium or potassium borohydride or sodium or potassium cyanoborohydride.
  • the products of general formula (I) can optionally be transformed into addition salts with mineral or organic acids.
  • the products of general formula (m) are generally obtained by reduction of the corresponding nitro derivative. More particularly, the products of general formula fl ⁇ ) in which one of the symbols j or R2 represents an alkoxycarbonyl, carbamoyl or thiocarbamoyl radical can be obtained according to known methods for the preparation of esters, amides or thioamides from corresponding nitro acid followed by reduction of the nitro derivative thus obtained.
  • protons of the nuclear magnetic resonance spectra are numbered according to the rules of the nomenclature.
  • the tbutyl ester of 5- (2,5-d ydroxybenzylidéneamino) salicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in Example 1. After purification by flash chromatography on silica gel, eluting with dichloromethane, the tbutyl ester of 5- (2,5-dihydroxybenzylamino) salicylic acid is obtained with a yield of 52%. the characteristics of which are as follows: - melting point: 115-116 ° C.
  • the 2,4,4-trimethylpentylic ester of 5- (2,5-dihyclroxybenzylidene amino) salicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in example 1.
  • the 2,4,4-trimethylpentyester is obtained with a yield of 83% 5- (2,5-dmydroxybenzylamino) salicylic acid, the characteristics of which are as follows: - melting point: 119-120 ° C - proton nuclear magnetic resonance spectrum (dimethylsulfoxide; chemical shifts in ppm; coupling constants J in Hz): 9.8 (s, 1H: OH);
  • the 2- (phenylethyl) ester of 5- (2,5-dihydro-tyber ⁇ zylidèneamino) salicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in Example 1.
  • the 2-phenylethyl ester of 5- (2,5-) acid is obtained with a yield of 91%.
  • dihydroxybenzylam o) salicylic the characteristics of which are as follows:
  • N-benzyl-5- (2,5-dihydroxybenzylidéneamino) salicylamide is reduced by hydrogen in the presence of nickel under the conditions described in Example 1.
  • N-benzyl-5- (2,5-dihydroxybenzylamino) salicylamide is obtained, with a yield of 80%, the characteristics of which are as follows:
  • N-2,4,4-trimethylpentyl-5- (2,5-dihydro is reduced by hydrogen in the presence of nickel under the conditions described in Example 1.
  • N-2,4,4-trimethylpentyl-5- (2,5-dihydro-tybenzyamino) salicylamide is obtained, with a yield of 90%, the characteristics of which are as follows:
  • N- (1-methoxycarbonyl-2- (4-hydroxyphenyl) ethylamide of 5- (2,5-dihydroxybenzylidene) aminosalicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in Example 1.
  • the N- (l -methoxycarbonyl-2- (4-hydroxyphenyl) ethylamide of 5- (2,5-dmydroxyben-tyl) arninosaIicylic acid the characteristics of which are as follows:
  • N- (benzyl) -5-nitrothiosalicylamide 1.5 g (5.21 mmol) of N- (benzyl) -5-nitrothiosalicylamide are stirred in methanol with Raney nickel, 50% in water, under hydrogen pressure from 1 atmosphere to that the reaction is complete. After filtration and washing with methanol, the filtrate is concentrated to dryness under reduced pressure. 1.3 g of N- (benzyl) -5-aminothiosalicylamide are thus obtained, with a yield of 97%, the characteristics of which are as follows: - melting point: 63 ° C.
  • the organic phase is washed successively with 2 times 50 cm3 of 4N hydrochloric acid, 2 times 50 cm3 of water, 3 times 50 cm3 of a 10% solution of sodium bicarbonate, 50 cm3 of water, 2 times 20 cm3 of a saturated solution of sodium chloride then dried over magnesium sulfate and evaporated under reduced pressure.
  • the residue is chromatographed on silica gel with x dichloromethane-hexane mixture (2-8 by volume) to give 4.1 g of 1- (2-hydroxy) phenyl-3,5,5-trimethylhexan-1-one (70 %), usable as is in the next step.
  • EXAMPLE 36 250 mg of the 3,5-dimethylbenzyl ester of 5-amino-salicylic acid (1.84 mmol; 1 equivalent) is condensed with 250 mg of 2,5-dihydroxy benzaldehyde (1.84 mmol; 1 éqxdvalent) by operating in methanol. The reaction mixture is stirred for 5 hours at a temperature in the region of 20 ° C. After treatment as in Example 1 and purification by recrystallization from methanol, there is obtained, with a yield of 90%, 650 mg of the 3,5-dimemylbenzylic ester of 5- (2,5-d ydroxybenzyKdéneamino acid). ) salicylic whose characteristics are the following:
  • N-phenylamide of 5- (2,5-dihydro-benzyHdéneamino) salicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in Example 1 in a methanol-dimethylformamide mixture. After purification by flash chromatography on silica gel, eluting with dichloromethane-methanol (50-1 by volume), then dichloromethane-methanol (20-1 by volume) and recrystallization from dichloromethane, a yield is obtained.
  • the N-phenylamide of 5- (2,5-dihydrOxybenzylamino) salicylic acid the characteristics of which are as follows: - melting point: 196-198 ° C. - proton nuclear magnetic resonance spectrum (dimethyl sulfoxide-d6; chemical shifts in ppm; coupling constants J in Hz): 10.68 (s, IH:
  • the 3,5,5-trimethylhexylic ester of 5- (2,5-dihydroxybenzylidene) aminosalicylic acid is reduced by hydrogen in the presence of nickel under the conditions described in Example 1.
  • N- ( ⁇ -methylbenzyl) amide is obtained with a yield of 71.6%.
  • 5- (2,5-dihydroxybenzyl) aminosalicylic acid the characteristics of which are as follows: -melting point: 190-192 ° C
  • the inhibitory activity of the new products according to the invention vis-à-vis the family of receptors of the epidermal growth factor (EGF) type can be demonstrated by using membranes expressing either the EGF-R receptor or the HER receptor -2 as a source of protein tyrosine kinase and a tridecapeptide as a phosphorylation accepting substrate.
  • EGF epidermal growth factor
  • the cell activity is determined by measuring the inhibition of the DNA synthesis of these cells.
  • the results obtained show that, in vitro, the prodxdts according to the invention manifest their inhibitory activity at concentrations generally less than 10 ⁇ M and qxd can be weaker than 0.1 ⁇ M and that, in vivo, the inhibition of growth cellxdaire manifests itself at concentrations which can be lower than 1 ⁇ M.
  • Mouse EGF 100 ng / ml
  • the tridecapeptide RRLIEDAEYAARG the membrane fraction of ER22 cells (obtained by transfection of Chinese hamster poximon fibroblasts (CCL39) with complementary DNA coding for the EGF-R receptor) and l ⁇ Ci of ⁇ 32 P [ATP] and inhibitors at micromolar concentrations.
  • the receptor (EGF-R) is first incubated with EGF for 30 minutes at 4 ° C pxds with the sample. The reaction is initiated by adding the peptide and ⁇ 32p [ATP] pxds the medium is incubated for 30 minutes at 4 ° C.
  • the reaction is stopped by adding 25 ⁇ l of 10% trichloroacetic acid (TCA) and 10 ⁇ l of BSA at 20 mg / ml.
  • TCA trichloroacetic acid
  • BSA BSA
  • the precipitated proteins are separated by centrifugation and the supernatant (40 ⁇ l) is distributed over the Whatman P81 phosphocellxdose papers (2 cm 2) which are immediately immersed in 30% acetic acid for 30 minutes and then 3 times 15 minutes in the 45% acetic acid and finally dried. Radioactivity is measured by liquid scintillation.
  • In vivo activity can be determined by performing cell culture
  • ER22 on a modified Dulbecco medium (DMEM) supplemented with 10% fetal calf serum (FCS) containing 200 ⁇ g / ml of antibiotic G418, at 35 ° C in an atmosphere containing 5% carbon dioxide.
  • DMEM Dulbecco medium
  • FCS fetal calf serum
  • the cells are distributed in wells at the rate of 3.5 ⁇ 10 -5 cells per well in 24-well trays.
  • the cells are cultured in xm DMEM medium supplemented with 10% FCS then in a DMEM / HAMS'F12 medium (1/1) for 48 hexires.
  • the cells are then incubated for 1 hour with different concentrations of the prodxdt to be studied. Then add growth factors or fetal calf serum and methyl H-thymidine (0.1 mCi ml). The incorporation of the tritiated thymidine into the fraction insoluble in trichloroacetic acid is determined by counting in liquid scintillation.
  • the new products of general formula (I) are particularly useful in human or veterinary therapy as inhibitors of tumor growth and proliferation and in tumor therapy. They are particularly useful in the treatment of melanomas, ovarian and mammary carcinomas or gliomas.
  • the new products of general form (I) are also useful in the treatment of phenomena related to memory disorders, epilepsy, stroke, Alzheimer's disease or Parkinson's disease .
  • Products of the general form (I) may also be useful in the treatment and prevention of AIDS.
  • prodxdts can be used in the treatment of certain forms of allergy, psoriasis linked to EGF, atherosclerosis, retinosis or myelofibrosis linked to PGDF.
  • Ri represents an alkyloxycarbonyl radical in which the alkyl part contains 1 to 10 carbon atoms and is optionally substituted by xm phenyl radical, xm aryloxycarbonyl radical, xm acyl radical optionally substituted by xm phenyl radical, an arylcarbonyl radical, a carbamoyl radical in which the nitrogen atom is substituted by an alkyl radical optionally substituted by a phenyl and / or alkoxycarbonyl radical and R2 represents x hydrogen or halogen atom or a hydroxy radical, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, mercapto, alkylthio, amino, formylamino, alkylcarbonylamino or atylcarbonylamino.
  • the present invention relates to pharmaceutical compositions which contain at least xm prodxdt of general formxde (I), optionally in salt form, in combination with x or more pharmaceutically acceptable diluents or adjuvants, inert or therapeutically active.
  • the pharmaceutically acceptable addition salts are chosen from salts with mineral acids such as hydrochloric, hydrobromic, nitric, hydrofluoric, phosphoric or organic acids such as acetic, formic, propionic, maleic, malonic, fumaric, succinic acids , tartaric, citric, oxalic, aspartic, methanesulfonic, ethanesulfonic, benzenesulfonic, p.toluenesxdfonic or benzoic optionally substituted.
  • the compositions according to the invention can be administered by oral, parenteral, rectal or topical route.
  • compositions for oral administration can be used tablets, pills, powders or granxconverges.
  • the products of general form (I) are mixed with one or more inert diluents such as sucrose, lactose or starch.
  • these compositions can also include substances other than diluents, for example a lubricant such as magnesium stearate.
  • compositions for oral administration pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing inert diluents such as water or paraffin oil can be used.
  • inert diluents such as water or paraffin oil
  • these compositions can also include substances other than diluents, for example wetting, sweetening or flavoring products.
  • compositions for parenteral administration can be aqueous or non-aqueous sterile solutions, suspensions or emulsions.
  • solvent or vehicle propylene glycol, polyethylene glycol, vegetable oils, in particular olive hxdle, and injectable organic esters, for example ethyl oleate can be used.
  • These compositions can contain adjuvants, in particular moxdllants, emxdsifiers and dispersants.
  • Sterilization can be done in several ways, for example using a bacteriological filter, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
  • compositions for rectal administration are suppositories which may contain, in addition to the active product, excipients such as cocoa bextrum.
  • compositions for topical application are generally creams, ointments or ointments. They can also be in the form of poxdtices.
  • the doses depend on the desired effect, on the time of treatment, on the route of administration and on the factors specific to the subject to be treated. They are generally between 10 and 500 mg per day parenterally for an adult.
  • Ampoules containing xme solution poxir intraperitoneal administration consisting of:

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
EP93910121A 1992-05-18 1993-05-14 Nouveaux derives de la dihydroxybenzylamine, leur preparation et les compositions pharmaceutiques qui les contiennent Withdrawn EP0641311A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9205980A FR2691145A1 (fr) 1992-05-18 1992-05-18 Nouveaux dérivés de la dihydroxybenzylamine, leur préparation et les compositions pharmaceutiques qui les contiennent.
FR9205980 1992-05-18
PCT/FR1993/000468 WO1993023364A1 (fr) 1992-05-18 1993-05-14 Nouveaux derives de la dihydroxybenzylamine, leur preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number Publication Date
EP0641311A1 true EP0641311A1 (fr) 1995-03-08

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EP93910121A Withdrawn EP0641311A1 (fr) 1992-05-18 1993-05-14 Nouveaux derives de la dihydroxybenzylamine, leur preparation et les compositions pharmaceutiques qui les contiennent

Country Status (8)

Country Link
EP (1) EP0641311A1 (enrdf_load_stackoverflow)
JP (1) JPH07506585A (enrdf_load_stackoverflow)
AU (1) AU4075693A (enrdf_load_stackoverflow)
FR (1) FR2691145A1 (enrdf_load_stackoverflow)
MX (1) MX9302869A (enrdf_load_stackoverflow)
TW (1) TW252095B (enrdf_load_stackoverflow)
WO (1) WO1993023364A1 (enrdf_load_stackoverflow)
ZA (1) ZA933426B (enrdf_load_stackoverflow)

Families Citing this family (10)

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Publication number Priority date Publication date Assignee Title
CA2321307A1 (en) * 1998-02-27 1999-09-02 Venkatachala L. Narayanan Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
US7166275B2 (en) * 2003-07-11 2007-01-23 Isp Investments Inc. Compositions containing phenethyl aryl esters as solubilizing agents for active organic compounds
US7208143B2 (en) * 2004-09-29 2007-04-24 Isp Investments Inc. Antiperspirant compositions
JP2006008642A (ja) * 2004-06-29 2006-01-12 Sumitomo Bakelite Co Ltd アミノフェノール化合物、熱硬化性化合物およびその製造法
EP1874723A2 (en) * 2005-04-15 2008-01-09 Dominion Pharmakine S.L. New nitrogenated trans-stilbene analogs, method for the obtention and medical applications thereof
CA3216096A1 (en) 2021-06-08 2022-12-15 Entheogenix Biosciences, Inc. Dimethoxyphenylalkylamine activators of serotonin receptors
KR20240019152A (ko) 2021-06-09 2024-02-14 아타이 테라퓨틱스, 인크. 신규 전구약물 및 디메틸트립타민의 접합체
WO2023129909A1 (en) 2021-12-27 2023-07-06 ATAI Life Sciences AG Aminotetraline activators of serotonin receptors
CA3238440A1 (en) 2021-12-30 2023-07-06 Atai Therapeutics, Inc. Dimethyltryptamine analogues as nitric oxide delivery drugs
WO2024229149A1 (en) 2023-05-01 2024-11-07 Atai Therapeutics Inc. Compositions and methods for treatment of diseases and disorders

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DE2120091A1 (de) * 1971-04-24 1972-11-09 Agfa-Gevaert Ag, 5090 Leverkusen Farbbildner für das Peroxid-Farbverstärkungs-Verfahren

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Title
See references of WO9323364A1 *

Also Published As

Publication number Publication date
FR2691145A1 (fr) 1993-11-19
MX9302869A (es) 1993-11-01
AU4075693A (en) 1993-12-13
JPH07506585A (ja) 1995-07-20
WO1993023364A1 (fr) 1993-11-25
ZA933426B (en) 1994-08-02
TW252095B (enrdf_load_stackoverflow) 1995-07-21

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