CN87103524A - Tetrahydro naphthaline derivatives - Google Patents
Tetrahydro naphthaline derivatives Download PDFInfo
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- CN87103524A CN87103524A CN198787103524A CN87103524A CN87103524A CN 87103524 A CN87103524 A CN 87103524A CN 198787103524 A CN198787103524 A CN 198787103524A CN 87103524 A CN87103524 A CN 87103524A CN 87103524 A CN87103524 A CN 87103524A
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- compound
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- naphthyl
- tetramethyl
- tetrahydrochysene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
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- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
The invention relates to the compound of general formula I, wherein R represent adjacent-,-or right-hydroxyphenyl; 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-dihydroxyphenyl; Or 2,3,4-, 2,3,5-, 2,4,5-, 2,4,6-, 3,4,5-or 2,3,6-three hydroxyphenyl, these compounds have the effect of treatment disease, and antitumor action is for example arranged.
Description
The invention relates to the novel tetrahydro naphthalene derivatives of formula I, wherein R
1Represent adjacent-,-or right-hydroxyphenyl; 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-dihydroxyphenyl; Or 2,3,4-, 2,3,5-, 2,4,5-, 2,4,6-, 3,4,5-or 2,3,6-three hydroxyphenyl.
The compound of formula I can trans or cis-isomeride or the existence of cis/trans isomer mixture.Usually, the trans-compound of formula I is best, and in those compounds, R be adjacent-,-or right-hydroxyphenyl, particularly right-hydroxyphenyl.
The present invention also relates to the compound of manufacture method, pharmaceutical preparation, anti-curing oncoma and the dermopathic formula I of generalformula, and use the compound manufacturing of formula I to prevent and treat the pharmaceutical preparation of these diseases according to the generalformula manufacturing.
According to the present invention, cut the compound that to make formula I, wherein R by the protecting group from the compound of general formula II
11Represent a kind of R
1Residue is shielded at the middle hydroxyl of R '.
All common hydroxyl protecting groups just begin to be considered as protecting group there.The example of this protecting group is an ethers, particularly 2-THP trtrahydropyranyl ether and silyl ether such as trimethyl silyl ether; Next alkyl oxide such as methyl ether; And ester, for example low chain alkyl carboxylic acid ester such as acetic ester and carbonic ether.With the method for just knowing originally, can finish the incision of protecting group by the processing of acid, alkali or reductive agent.By tosic acid or Lewis acid (as BF
3Or BBr
3) acid treatment can cut ether protecting group such as THP trtrahydropyranyl and trimethyl silyl.Alkaline purification for example alcohol or aqueous alcoholic alkali hydroxide soln can cut the ester protecting group as acetic ester or carbonic ether.
The reaction of the compound of the compound of general formula III and general formula IV can obtain the compound of general formula II,
Wherein A is not a kind of-CH(CH of representative
3)
P+(Q) Y
-Residue is represented-CH(CH exactly
3) P(O) (OAlK)
2, B represents formyl, or A represents acetyl and a kind of-CH of B representative
2P
+(Q)
3Y
-Or-CH
2P(O) (OAlK)
2Residue; Q represents aryl, especially phenyl.Y
-The negatively charged ion of representing a kind of organic acid or mineral acid, for example Br
-, AlK represents for example methyl of low alkyl group, R
11The same.
Love and respect one's elder brother (Witting) or Huo Ener (Horner) reaction method can carry out the reaction of the compound of general formula III and IV according to known dimension.
Under dimension is loved and respect one's elder brother the situation of reaction, i.e. A=-CH(CH in using the general formula III
3) P
+(Q)
3Y
-With B=-CH in the general formula IV
2P
+(Q)
3Y
-The situation of compound under, range of reaction temperature is between the boiling point of room temperature and reaction mixture, having under the situation of acid wedding agent simultaneously, the sodium salt of alkaline butyllithium, sodium hydride or methyl-sulphoxide for example, and especially at the oxyethane that has any low alkyl group to replace as 1, the 2-butylene oxide ring at random is dissolved in a kind of solvent, for example be dissolved in a kind of ether such as ether or tetrahydrofuran (THF) or be dissolved in aromatic hydrocarbon such as benzene in situation under, these components react mutually.
Chlorion, bromide anion or hydrogen sulfate ion are best inorganic acid ion Y
-, the tosyloxy ion is best organic acid ion.This aromatic residues Q is preferably the phenyl residue such as the right-tolyl of phenyl residue or a kind of replacement.
Under the situation of Huo Ener reaction, i.e. A=CH(CH in using the general formula III
3)-P(O) (OAlK)
2With B=-CH in the general formula IV
2P(O) (OAlK)
2The situation of compound under, temperature range is between the boiling point of 0 ° and reaction mixture, being preferably in simultaneously under the organic solvent inert situation concentrates component with a kind of alkali, for example with being dissolved in benzene, toluene, dimethyl formamide, tetrahydrofuran (THF), diox or 1, sodium hydride in the 2-glycol dimethyl ether, or also availablely be dissolved in the sodium alkoxide of alkanol, for example be dissolved in the sodium methylate of methyl alcohol.
Alcoxyl residue OAlK is the very rudimentary alcoxyl residue with 1～6 carbon atom, for example methoxy or ethoxy.
The compound of formula I may reside in trans or the cis form among.Mainly be the compound that obtains trans form in the method.If necessary, can obtain the cis component with known method separation.
Do not knowing or hereinafter do not having to introduce how to prepare under the situation of general formula III and IV raw material, can prepare these raw materials with being similar to known method or being similar to the method for hereinafter introducing.
Some compounds of formula I have therapeutic action.Especially, they have seborrhea, anti-angling, anti-knurl and anti-allergy and antiphlogistic effect, can prove these effects with the test method of hereinafter introducing:
A) can define the chest knurl effect that prevents that chemistry from causing according to following method.Female Si Pala fine jade-Dao Li (Sprague-Dawley) mouse is not given drinking-water and food simultaneously under temperature control and light-operated condition.Give 15 milligrams of dimethylbenzene anthracenes that are dissolved in peanut oil of every mouse administration in 50 day age with probang.Daystart after giving carcinogens is handled with test compound.The body weight of record experimental animal is checked tumour weekly one time, and with vernier caliper measurement tumour size.According to formula (D)/2 d
2Calculate tumor size, D represents the ellipsoidal major diameter of tumour in the formula, and d represents the ellipsoidal minor axis of tumour.After 11 week, finish this test and test is calculated.In this test, except the contrast mouse that eats normal diet with 30, also use following two groups of experimental animals:
1. give 30 milligrams/kilogram of 33 mouse administrations and food blended test compounds every day.
2. give 90 milligrams/kilogram of 36 mouse administrations and food blended test compounds every day.
B) in addition, according to following method, with the effect of the mouse cartilage tumor mensuration of transplanting to tumour.Shred the solid tumor of donor animal carefully, and it is suspended in phosphoric acid buffer and the sodium chloride solution.Be injected on one's body the mouse that suffers from piebaldism 0.5 milliliter 30% tumour suspension is subcutaneous.
It is the test group of a case that the mouse of transplanting is divided into per 8.Test compound is suspended in the peanut oil, and per week is given oral 5 times of mouse, totally 24 days.Cut tumours and gave weighing by 24 days.Represent these results with the C/T quotient, according to the quotient of following calculating C/T:
(C)/(T)=(the average tumor weight of contrast)/(with the average tumor weight of test compound processing)
C), also can measure anti-metaplastic effect with mouse according to following method.After 8 day adaptive phase, the ovary of female Huo Erziman (Holtzmann) mouse of about 100 grams of excision body weight under the condition of proposing Yue Jienaier (Thiogenal) anesthesia, after 14 days, these mouse are used for test again.In each case, two mouse are placed in the cage, do not feed and give the vitamin A food (using chemical gauging) that contains about 2000 international unit.Before the oral test compound, to mouse make subcutaneous treatment, continuous 6 day with 1 microgram progynon B (estradiol benzoate) and the 250 microgram testovirons that are dissolved in 0.1 milliliter of sesame oil every day.Hormone parenteral administration causing vaginal smear produces tangible particulate state stage, i.e. flaky metaplasia.Later 2 days of oral test compound, read the result of this reaction again at vagina epithelium.Adopt the field method of Bei Leisi (Behrens) and card primary (karber) to calculate average effective dose.
In following table I-III, listed a kind of compound with formula I right-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) the A-C test-results of phenol.
The table I
A) the chest tumour that chemically causes of prevention
Dosage has every mouse of every mouse tumour of mouse of tumour on average swollen
The mean number knurl volume millimeter of (milligram/litre) (%)
3
P.O. (contrast %) (contrasting %)
30????68????52.4????72.6
90????35????14.1????3.9
The table II
B) to the chondrosarcomatous effect of transplantable mouse
Be untreated comparing animals and handle animal of dosage
The merchant C/T of the tumor weight of (milligram/kilogram)
P.O.
120????3.8
The table III
C) the intravital anti-metaplasia effect of mouse
The compound relative activity
All trans retinoic acids 1
Chemical compounds I 0.91
The compound of formula I can be used for treating the optimum and virulent tumour of local and whole body, treats premalignant infringement, and also can be used for preventing above-mentioned whole body and partial disease.
And this compound is suitable for treating acne, psoriasis and other tetter of local and whole body, and the keratinization with changing on simultaneous that reinforcement promptly arranged or the pathology of these diseases has inflammatory and allergic skin focus again.In addition, some compounds of formula I also can be used for controlling the mucous membrane disease with inflammatory or sex change or metaplasia variation.Especially, the compound of formula I and known retinoids compare, and its characteristics are that toxicity is low or tolerance is high.
These pharmaceutical preparations can intestines in, parenteral or administration partly.With regard to administration in the intestines, its suitable dosage form has tablet, capsule, drageeing, syrup, suspension, solution and suppository.The preparation of preserved material or injection solution form all is applicable to the parenteral dispenser.
The preparation dosage both can can be changed according to patient's needs again according to the mode of using and the approach of use.Usually, the per daily dose of considering for the grownup approximately is 0.1～50 milligram/kilogram, is preferably 1-15 milligram/kilogram.
Preparation can be by dose or dosed administration several times.The capsule that contains about 5-200 milligram active substance is a kind of administering mode of the best.
Preparation can contain active additive on inert or the drug effect.For example tablet or pill can contain a series of tackiness agents, filler, carrier substance or thinner.The existence form of liquid preparation be a kind of can with water blended sterile solution.Capsule can contain filler or thickening material except active substance.And, also can contain sweet-scented additive and usually as salt, buffer reagent and other additives of anticorrosion, stable, water conservation and emulsive reagent, change osmotic pressure.
Above-mentioned carrier and thinner can be the materials of organic or inorganic, for example water, gelatin, lactose, starch, Magnesium Stearate, talcum powder, Sudan Gum-arabic and polyglycol etc.The prerequisite of all auxiliarys that use when making preparation be do not have toxic.
With regard to active substance was used in the part, forms such as ointment, medicinal liquor, emulsifiable paste, solution, lotion, sprays and suspension were easy to use.And best be ointment, emulsifiable paste and solution.By the compound as the formula I of activeconstituents is mixed with carrier, can produce preparation for the part use, employed carrier is in preparation and that be applicable to Local treatment and is nontoxic, inert, solid and liquid support.
With regard to used the part, about 0.1～5% solution was quite easily, and 0.3～2% is best, and about 0.1～5% ointment or emulsifiable paste be quite easily, and about 0.3～2% is best.
If necessary, pharmaceutical preparation can contain a kind of antioxidant, for example tocopherol, N-methyl-γ-tocopherylamine, fourth BHA (butylated hydroxyanisole) or 2,6 ditertiary butyl p cresol.
Some following examples have further been illustrated situation of the present invention.Given temperature is Celsius.
Example 1
Right-(2-(5,6,7,8-tetrahydrochysene 5,5,8, the 8-tetramethyl--2-naphthyl) propenyl of 82.3 grams) phenylacetate is suspended in 2 liters the ethanol, and adds the solution of 600 ml waters that contain 130 gram potassium hydroxide to the there.In stirring at room after 1 hour, with this mixture of hcl acidifying of dilution, use ice-cooledly simultaneously, and extract repeatedly with ethyl acetate.Water cleans organic phase four times, carries out drying and evaporated on sodium sulfate.Can from hexane/ethyl acetate, go out the crystal resistates by recrystallize, and obtain 66 grams right-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol, its fusing point is 140-142 °.
Can prepare starting material as follows:
With 360 gram (1-(5,6,7,8-tetrahydro--5,5,8,8-tetramethyl--2-naphthyl) ethyls)-three phenyl phosphonium bromides are suspended in 500 milliliters the tetrahydrofuran (THF), and handle with 410 milliliters of n-Butyl Lithiums (1.6 moles are dissolved in the hexane) at 0 °.0 ° stir 1 hour after, add the solution of 300 milliliters of tetrahydrofuran (THF)s that contain 94.5 gram 4-acetoxyl-phenyl aldehydes toward the there, and at room temperature this mixture restir 2 hours.Then, this reaction mixture is injected 2 liters of methanol (6: 4), and extract repeatedly with hexane.Water cleans organic phase three times, after with dried over sodium sulfate, evaporates.Go up filtration residue and from hexane, after the crystallization, obtain right-(2-(5,6 of 83 gram clear crystals at silica gel (eluent hexane/ethyl acetate=9.1), 7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenylacetate, fusing point is 114～116 °.
Example 2
Similar to example 1, by-(2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) between propenyl) hydrolysis of phenylacetate is made-((E)-and 2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol, fusing point is 91～93 °.
Example 3
Similar to example 1, by adjacent-(2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) hydrolysis of naphthyl acetate make adjacent-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol, fusing point is 97～99 °.
Use general method, for example can make the pharmaceutical preparation of the dosage form that contains generalformula according to following example.
Example A
Hard gelatin capsule is produced as follows:
Composition milligram/capsule
1. contain the dried spraying of 75% chemical compounds I
Powder 200
2. the dioctyl sodium sulfosuccinate 0.2
3. Xylo-Mucine 4.8
4. Microcrystalline Cellulose 86.0
5. talcum powder 8.0
6. Magnesium Stearate 1.0
Total amount 300
Get wet based on dried spraying powder, gelatin and the Microcrystalline Cellulose of active substance and the active substance of average particle size particle size＜1 μ (measuring) with the aqueous solution of Xylo-Mucine and dioctyl sodium sulfosuccinate, then they are kneaded with the positive spectrographic technique of autocorrelation.Make resulting material grainsization, dry and screening, and the particle that obtains is mixed with Microcrystalline Cellulose, talcum powder and Magnesium Stearate.This powder is clogged in No. 0 capsule.
Example B
Can produce tablet as follows:
Composition milligram/sheet
1. the powder 500 of levigated chemical compounds I
2. lactose powder 100
3. white W-Gum 60
（Maize????Starch????white）
4. polyvinylpyrrolidone K30 8
4. white W-Gum 112
5. talcum powder 16
6. Magnesium Stearate 4
Summation 800
The levigated material is mixed with lactose and part W-Gum.With the aqueous solution of polyvinylpyrrolidone K30 this mixture of getting wet, kneaded then, and made the material grainsization that obtains, dry and screening.This particle is mixed with remaining W-Gum, talcum and Magnesium Stearate, and be pressed into the tablet of corresponding size.
Example C
Can produce soft gelatine capsule as follows:
Composition milligram/capsule
1. chemical compounds I 50
2. triglyceride level 450
Summation 500
Digest compound I summation stirring and dissolving to 90 with 10 and restrain in the medium chain triglyceride, and carry out the inertia pneumatolysis, cover light.This solution is processed into the capsule packing material of the soft gelatin capsule that contains 50 milligrams of active substances.
Example D
Can prepare a kind of washing lotion as follows:
Composition
1. levigated chemical compounds I 3.0 restrains
2. block vigorous bohr 934 0.6 grams
（Carbopol）
3. sodium hydroxide is in right amount to PH6
4.94% ethanol, 50.0 grams
5. softening water to 100.0 restrains
Covering under the condition of light, active substance is added in the mixture of 94% second alcohol and water.Stir the vigorous bohr 934 of card, finish until pectisation, and adjust pH value with sodium hydroxide.
Claims (14)
1, a kind of method for preparing generalformula,
Wherein R ' represent adjacent-,-or to hydroxyphenyl; 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-dihydroxyphenyl; Or 2,3,4-, 2,3,5-, 2,4,5-, 2,4,6-, 3,4,5-or 2,3,6-three hydroxyphenyl, this method comprise the protecting group of cutting general formula II compound,
Wherein " expression R ' residue, wherein hydroxyl is shielded to R.
2, according to the process of claim 1 wherein that the two keys of alkene of compound of formula I and II have transconfiguration.
3, the process of claim 1 wherein preparation right-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol.
4, the process of claim 1 wherein between preparation-((E)-and 2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol.
5, the process of claim 1 wherein preparation adjacent-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol.
6, a kind of manufacture method of pharmaceutical preparation, wherein the compound of formula I is with a kind of pharmaceutical carrier chemical combination.
7, the pharmaceutical preparation that contains generalformula and pharmaceutical carrier.
8, use the compound manufacturing treatment tumour and the dermopathic pharmaceutical preparation of formula I.
9, whenever with the method for claim 1 or with the compound of its tangible chemical equivalent preparation formula I the time,
R wherein
1Expression is adjacent-,-or right-hydroxyphenyl; 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-dihydroxyphenyl; Or 2,3,4-, 2,3,5-, 2,4,5-, 2,4,6-, 3,4,5-or 2,3,6-three hydroxyphenyl.
10, according to the compound of claim 1, when preparing compound with the method for claim 2 or with its tangible chemical equivalent, wherein the two keys of alkene have transconfiguration.
11, always prepare right-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl with the method for claim 3 or with its tangible chemical equivalent at every turn) phenol.
12, each always with the method for claim 4 or with between its tangible chemical equivalent preparation-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol.
13, each always with the method for claim 5 or with its tangible chemical equivalent preparation adjacent-((E)-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) propenyl) phenol.
14, content of the present invention as mentioned above.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH01938/86-3 | 1986-05-13 | ||
| CH1938/86A CH668962A5 (en) | 1986-05-13 | 1986-05-13 | New hydroxy:phenyl:propenyl substd. naphthalene cpds. |
| CH00742/87-0 | 1987-02-26 | ||
| CH74287 | 1987-02-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN87103524A true CN87103524A (en) | 1987-12-02 |
Family
ID=25685550
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN198787103524A Pending CN87103524A (en) | 1986-05-13 | 1987-05-12 | Tetrahydro naphthaline derivatives |
Country Status (20)
| Country | Link |
|---|---|
| CN (1) | CN87103524A (en) |
| AU (1) | AU7277987A (en) |
| BE (1) | BE1001668A5 (en) |
| DE (1) | DE3715809A1 (en) |
| DK (1) | DK232087A (en) |
| ES (1) | ES2005572A6 (en) |
| FI (1) | FI872027A (en) |
| FR (1) | FR2598706B1 (en) |
| GB (1) | GB2190378B (en) |
| HU (1) | HU198002B (en) |
| IL (1) | IL82448A0 (en) |
| IT (1) | IT1203954B (en) |
| LU (1) | LU86866A1 (en) |
| MC (1) | MC1817A1 (en) |
| NL (1) | NL8701101A (en) |
| NO (1) | NO871961L (en) |
| NZ (1) | NZ220215A (en) |
| PT (1) | PT84860B (en) |
| SE (1) | SE8701933L (en) |
| ZW (1) | ZW6587A1 (en) |
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| US5675024A (en) | 1995-11-22 | 1997-10-07 | Allergan | Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thiochroman and 1,2,3,4,-tetrahydroquinoline carboxylic acids, having an electron withdrawing substituent in the aromatic or heteroaromatic moiety, having retinoid-like biological activity |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4326055A (en) * | 1977-12-22 | 1982-04-20 | Hoffmann-La Roche Inc. | Stilbene derivatives |
| CA1162200A (en) * | 1981-02-13 | 1984-02-14 | Michael Klaus | Process for the manufacture of indanyl (or tetrahydronaphthyl)propenyl phenyl derivatives |
| DE3202100A1 (en) * | 1982-01-23 | 1983-08-04 | Basf Ag, 6700 Ludwigshafen | SUBSTITUTED 4-HYDROXYANILIDES, ITS PRODUCTION AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM |
| EP0084667B1 (en) * | 1982-01-23 | 1985-09-18 | BASF Aktiengesellschaft | Phenylethylene derivatives, their preparation and use as medicines |
| DE3602473A1 (en) * | 1986-01-28 | 1987-07-30 | Basf Ag | VINYLPHENOL DERIVATIVES, THEIR PRODUCTION AND USE |
-
1987
- 1987-04-10 ZW ZW65/87A patent/ZW6587A1/en unknown
- 1987-04-23 IT IT20232/87A patent/IT1203954B/en active
- 1987-05-06 DK DK232087A patent/DK232087A/en not_active Application Discontinuation
- 1987-05-06 NZ NZ220215A patent/NZ220215A/en unknown
- 1987-05-06 LU LU86866A patent/LU86866A1/en unknown
- 1987-05-07 IL IL82448A patent/IL82448A0/en unknown
- 1987-05-07 FI FI872027A patent/FI872027A/en not_active Application Discontinuation
- 1987-05-08 NL NL8701101A patent/NL8701101A/en not_active Application Discontinuation
- 1987-05-11 SE SE8701933A patent/SE8701933L/en not_active Application Discontinuation
- 1987-05-11 HU HU872103A patent/HU198002B/en not_active IP Right Cessation
- 1987-05-11 BE BE8700505A patent/BE1001668A5/en not_active IP Right Cessation
- 1987-05-11 MC MC871883A patent/MC1817A1/en unknown
- 1987-05-11 FR FR878706564A patent/FR2598706B1/en not_active Expired - Fee Related
- 1987-05-12 PT PT84860A patent/PT84860B/en not_active IP Right Cessation
- 1987-05-12 GB GB8711205A patent/GB2190378B/en not_active Expired - Fee Related
- 1987-05-12 NO NO871961A patent/NO871961L/en unknown
- 1987-05-12 CN CN198787103524A patent/CN87103524A/en active Pending
- 1987-05-12 ES ES8701419A patent/ES2005572A6/en not_active Expired
- 1987-05-12 AU AU72779/87A patent/AU7277987A/en not_active Abandoned
- 1987-05-12 DE DE19873715809 patent/DE3715809A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| NL8701101A (en) | 1987-12-01 |
| IT1203954B (en) | 1989-02-23 |
| PT84860B (en) | 1990-02-08 |
| HU198002B (en) | 1989-07-28 |
| HUT43806A (en) | 1987-12-28 |
| NO871961L (en) | 1987-11-16 |
| FR2598706B1 (en) | 1990-07-06 |
| ES2005572A6 (en) | 1989-03-16 |
| MC1817A1 (en) | 1988-03-18 |
| GB2190378A (en) | 1987-11-18 |
| ZW6587A1 (en) | 1987-12-02 |
| FI872027A (en) | 1987-11-14 |
| DK232087A (en) | 1987-11-14 |
| IT8720232A0 (en) | 1987-04-23 |
| FI872027A0 (en) | 1987-05-07 |
| DE3715809A1 (en) | 1987-11-19 |
| PT84860A (en) | 1987-06-01 |
| SE8701933D0 (en) | 1987-05-11 |
| LU86866A1 (en) | 1988-06-13 |
| NZ220215A (en) | 1990-06-26 |
| FR2598706A1 (en) | 1987-11-20 |
| IL82448A0 (en) | 1987-11-30 |
| AU7277987A (en) | 1987-11-19 |
| BE1001668A5 (en) | 1990-02-06 |
| SE8701933L (en) | 1987-11-14 |
| NO871961D0 (en) | 1987-05-12 |
| DK232087D0 (en) | 1987-05-06 |
| GB8711205D0 (en) | 1987-06-17 |
| GB2190378B (en) | 1990-11-14 |
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