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GB1584298A - Indane carboxylic acid derivatives - Google Patents

Indane carboxylic acid derivatives Download PDF

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Publication number
GB1584298A
GB1584298A GB51699/77A GB5169977A GB1584298A GB 1584298 A GB1584298 A GB 1584298A GB 51699/77 A GB51699/77 A GB 51699/77A GB 5169977 A GB5169977 A GB 5169977A GB 1584298 A GB1584298 A GB 1584298A
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Prior art keywords
indane
carboxylic acid
group
phenyl
acetamido
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GB51699/77A
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Merck Sante SAS
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LIPHA SAS
LIPHA Liyonnaise Industrielle Pharmaceutique
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Publication of GB1584298A publication Critical patent/GB1584298A/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/02—Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/28—Halogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Rheumatology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Furan Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The preparation of the carboxylic acids derived from indane represented by the formula: <IMAGE> in which R has the meaning given in Claim 1, in the free form, of their therapeutically acceptable salts, and of certain of their amino esters and carboxamides are described. Indane which is free of substituent on the benzene ring but which carries a -COO(lower alkyl) group in place of the -COOH group is reacted with a halide R-C(O)-hal according to the Friedel-Crafts reaction, and the ester group of the intermediate compound obtained is saponified. The final product can be converted to its amino ester and dialkylaminoalkylcarboxamide by standard reactions. Substituents can also be introduced into the group R = phenyl. The compounds of formula I and their described derivatives are antiinflammatory, analgesic and platelet antiaggregating medicaments.

Description

(54) INDANE CARBOXYLIC ACID DERIVATIVES (71) We, LIPHA, LYONNAISE INDUSTRIELLE PHARMACEUTIQUE, a French body corporate, of 115, avenue Lacassagne, 69003 Lyon, France, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to indane carboxylic acid derivatives having pharmacological activity, to pharmaceutical compositions containing them and to processes for their manufacture.
The indane carboxylic acid derivatives with which the present invention is concerned are those represented by the general formula:
wherein R represents an acetamido - halophenyl (e.g. acetamido - chlorophenyl), alkylsulphonyl - phenyl (e.g. methylsulphonyl - phenyl), dialkylaminosulphonyl phenyl, for example dimethylaminosulphonyl - phenyl, or sulphamido - phenyl group; a dihalo - thienyl group or a furyl radical substituted by a lower alkyl group, for example methyl.
The term "lower alkyl" is used herein as meaning an alkyl group containing from 1 to 4 carbon atoms.
The lower alkyl esters, for instance the methyl and ethyl esters, and the pharmaceutically acceptable acid addition salts of the acids of formula I are also included within the scope of the present invention.
Compounds falling within the definition of formula I include: 5 - (4' - methylsulphonyl - benzoyl) - indane - 2 - carboxylic acid 5 - (4' - sulphamido - benzoyl) - indane - 2 - carboxylic acid 5 - (4' - dimethylaminosulphonyl - benzoyl) - indane - 2 - carboxylic acid 5 - (4' - acetamido - 3' - chloro - benzoyl) - indane - 2 - carboxylic acid 5 - [2' - (4",5" - dichlorothenoyl)] - indane - 2 - carboxylic acid and 5 - [2' - (5" - methylfuroyl)] - indane - 2 - carboxylic acid.
The present invention also includes within its scope substituted aminoesters, for example the di-lower alkylamino or di-lower alkyl - amino - lower alkyl esters, of the acids of formula I. Thus in accordance with another aspect of the invention there are provided the aminoesters of indane carboxylic acid derivatives represented by the general formula:
wherein R has the same meaning as in formula I and Am represents a dialkylamino or dialkylaminoalkyl group, and pharmaceutically acceptable acid addition salts of said aminoesters.
The present invention further includes within its scope the substituted amides of the acids of formula I. Thus in accordance with a further aspect of the invention there are provided the amides of indane carboxylic acid derivatives represented by the general formula:
wherein R has the same meaning as in formula I and Am' represents a dialkylaminoalkyl group, and pharmaceutically acceptable acid addition salts of said amides.
The compounds of the invention as represented by formula I may be prepared by reacting in accordance with the Friedel-Crafts reaction a compound of the general formula:
in which R' is a lower alkyl group, with an acid halide of the general formula: R-COX V in which R has the same meaning as in formula I and X is halogen, to form a compound of the general formula:
and thereafter subjecting the compound of formula VI to alkaline hydrolysis to obtain the required acid of formula I.
The Friedel-Crafts reaction may be carried out with or without solvent, but preferably with a suitable solvent, for example methylene chloride or carbon disulphide, at a temperature in the range from OOC. to the boiling point of the solvent, preferably to the refluxing temperature of the solvent. Among the Lewis acids which can be used, aluminium chloride is preferred. The reactants can be present in stoichiometric quantities or excess, and preferably in excess as regards the acid halide and the aluminium chloride, it being possible for this excess to extend to up to 4000/,.
As regards the compounds in which R is a phenyl group substituted by a sulphamido or dialkylaminosulphonyl radical, there can be used initially an ester of the general formula:
in which R' is a lower alkyl group and R" is a phenyl group substituted by an amino radical.
The compound of formula VII is subjected to a diazotisation by procedures known per se, and then the resulting aryl diazonium salt is treated with a solution of sulphur dioxide in acetic acid in the presence of a copper salt, preferably cupric chloride, so as to obtain a compound of the general formula:
in which R' has the same meaning as previously and R"' is a phenyl radical substituted by a chlorosulphonyl radical. The compound of formula VIII is then treated with ammonia, either in gaseous form or in solution in water or in a lower alkanol, to obtain the required compound of formula I in which R is a phenyl group substituted by a sulphamido radical. If the ammonia is replaced by a dialkylamine, for example dimethylamine, a compound of formula I is obtained in which R is a phenyl group substituted by a dialkylaminosulphonyl radical.
The compounds of the invention have been found to exhibit in the animal body anti-inflammatory, analgesic and platelet non-aggregating activity likely to render them of utility as anti-inflammatory, analgesic and anti-pyretic agents in human chemotherapeutics.
The compounds of the invention will generally be administered for chemotherapeutic use in the form of a pharmaceutical composition comprising a therapeutically active compound of the invention in association with a pharmaceutical carrier or excipient therefor. The composition is advantageously made up in a dosage unit form appropriate to the desired mode of administration.
Thus for oral administration the dosage unit may be a tablet or capsule; for parenteral administration it may be an injectable solution in a sealed container such as an ampoule; and for rectal administration it may be a suppository. Each dosage unit may contain, for example, from 50 to 500 mg. of the active ingredient.
The following Examples illustrate the invention.
EXAMPLE 1 5-(4'-Sulphamidobenzoyl)-indane-2-carboxylic acid
(a) Methyl 5 - (4' - chlorosulphonylbenzoyl) - indane - 2 - carboxylate Into a 250 ml reactor having stirring means, a thermometer and a dropping funnel were introduced 14.7 g (0.05 mol) of methyl 5 - (4' - aminobenzoyl) indane - 2 - carboxylate. At a temperature which was between 0 and 10"C. there were added 40 ml of 24 /n hydrochloric acid and then, at between 0 and 5 C., a solution of 3.8 g of sodium nitrite in 10 ml of water. The diazonium salt thus formed was thereafter added at about 15"C. and while stirring to a mixture of 80 ml of acetic acid saturated with sulphur dioxide and 2.8 g of cupric chloride dissolved in 5 ml of water. The resulting solution was allowed to return to ambient temperature and was then warmed at about 40"C. to complete the reaction and left to stand overnight. The following day, it was taken up in water and ice and the solid which precipitated was suction filtered.
(b) Methyl 5 - (4' - sulphamidobenzoyl) - indane - 2 - carboxylate
Into a 500 ml reactor having stirring means, a condenser and a dropping funnel were introduced 15.6 g (0.041 mol) of the compound obtained in the manner described in (a) and 150 ml of chloroform and therafter, while stirring well, 100 ml of 15% ammonia were added. Stirring was continued for IT hours at ambient temperature and the resulting substance was taken up in water and chloroform.
The chloroform phase was decanted, dried over sodium sulphate, filtered and concentrated. By recrystallising the residue from a mixture of ethyl acetate and diisopropyl ether, a solid was obtained which melted at 147 to 149"C. (capillary tube).
(c) Alkaline hydrolysis of the compound obtained in the manner described in (b), followed by recrystallisation of the product from a mixture of acetic acid and water, yielded the desired final product as a solid which melts at 157--1580C.
(capillary tube).
By replacing the ammonia used in step (b) by diethylamine the following compound was prepared in the same way: 5 - (4' - dimethylaminosulphonyl - benzoyl) - indane - 2 - carboxylic acid M.P.: 144--145"C. (capillary tube).
EXAMPLE 2 Ethvl (4'-Acetamido-3'-chloro-benzovl)-indane-2-carboxylate
Into a 250 ml reactor with stirring means, a condenser, a dropping funnel and a thermometer were introduced 8.8 g (0.025 mol) of ethyl (5 - (4' acetamidobenzoyl) - indane - 2 - carboxylate and 30 ml of acetic acid. At a temperature in the region of 10 C. were added 40 ml of chlorine-saturated acetic acid. The initial suspension progressively disappeared. The temperature was allowed to return for 1 hour to ambient temperature and then the acetic acid was concentrated under vacuum. An oil was obtained which, by recrystallisation from a mixture of hexane and ethyl acetate, yielded the desired product as a solid which melted at 126--1270C. (capillary tube).
EXAMPLE 3 5-[2'-(4",5"-Dichlorothenoyl)]-indane-2-carboxylic acid
Into a 250 ml reactor equipped with a stirring means, a condenser, a dropping funnel and a tube permitting the bubbling of gas into a reaction medium in the reactor were introduced 5.2 g (0.017 mol) of 5 - [2' - (4" - chlorothenoyl)] indane - 2 - carboxylic acid. At about 15"C., a solution of 27 ml of chlorinesaturated acetic acid was added. Heating then took place on a water bath at about 75"C., while causing chlorine to bubble into the reaction mixture. After cooling, a solid was isolated by suction filtering. This solid, when recrystallised from ethyl acetate, had a melting point of 190192 C. (capillary tube).
The following Table gives the melting or boiling points of compounds of the invention.
"C 5 - (4' - methylsulphonylbenzoyl) - indane - 2 carboxylic acid mp. 187-190 5-[2' - (5" - methylfuroyl)] - indane - 2 - carboxylic acid mp. 128-130 Methyl ester, bp. 195-205 (1 mm Hg) ; EXAMPLE 4 Tablets were prepared in accordance with known pharmaceutical techniques from the following constituents: Constituent mg. per tablet 5 - [2' - (4",5" - dichloro)- thenoyll - indane - 2 diethylaminoethylcarboxylate 200 Lactose 30 Wheat starch 29 Talc 10 Gelatin 5 Alginic acid 20 Starch 5 Magnesium stearate 300 mg.
WHAT WE CLAIM IS: 1. Indane carboxylic acid derivatives represented hy the general formula:
wherein R represents an acetamido - halophenyl, alkylsulphonyl - phenyl, dialkylaminosulphonyl - phenyl or sulphamido - phenyl group; a dihalo - thienyl group; or a furyl radical substituted by a lower alkyl group, and the lower alkyl esters and pharmaceutically acceptable acid addition salts thereof.
2. Indane carboxylic acid derivatives as claimed in Claim 1, wherein R represents an acetamido - chlorophenyl group, a methylsulphonyl - phenyl or
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (14)

  1. **WARNING** start of CLMS field may overlap end of DESC **.
    Into a 250 ml reactor with stirring means, a condenser, a dropping funnel and a thermometer were introduced 8.8 g (0.025 mol) of ethyl (5 - (4' acetamidobenzoyl) - indane - 2 - carboxylate and 30 ml of acetic acid. At a temperature in the region of 10 C. were added 40 ml of chlorine-saturated acetic acid. The initial suspension progressively disappeared. The temperature was allowed to return for 1 hour to ambient temperature and then the acetic acid was concentrated under vacuum. An oil was obtained which, by recrystallisation from a mixture of hexane and ethyl acetate, yielded the desired product as a solid which melted at 126--1270C. (capillary tube).
    EXAMPLE 3 5-[2'-(4",5"-Dichlorothenoyl)]-indane-2-carboxylic acid
    Into a 250 ml reactor equipped with a stirring means, a condenser, a dropping funnel and a tube permitting the bubbling of gas into a reaction medium in the reactor were introduced 5.2 g (0.017 mol) of 5 - [2' - (4" - chlorothenoyl)] indane - 2 - carboxylic acid. At about 15"C., a solution of 27 ml of chlorinesaturated acetic acid was added. Heating then took place on a water bath at about 75"C., while causing chlorine to bubble into the reaction mixture. After cooling, a solid was isolated by suction filtering. This solid, when recrystallised from ethyl acetate, had a melting point of 190192 C. (capillary tube).
    The following Table gives the melting or boiling points of compounds of the invention.
    "C 5 - (4' - methylsulphonylbenzoyl) - indane - 2 carboxylic acid mp. 187-190 5-[2' - (5" - methylfuroyl)] - indane - 2 - carboxylic acid mp. 128-130 Methyl ester, bp. 195-205 (1 mm Hg) ; EXAMPLE 4 Tablets were prepared in accordance with known pharmaceutical techniques from the following constituents: Constituent mg. per tablet
    5 - [2' - (4",5" - dichloro)- thenoyll - indane - 2 diethylaminoethylcarboxylate 200 Lactose 30 Wheat starch 29 Talc 10 Gelatin 5 Alginic acid 20 Starch 5 Magnesium stearate 300 mg.
    WHAT WE CLAIM IS: 1. Indane carboxylic acid derivatives represented hy the general formula:
    wherein R represents an acetamido - halophenyl, alkylsulphonyl - phenyl, dialkylaminosulphonyl - phenyl or sulphamido - phenyl group; a dihalo - thienyl group; or a furyl radical substituted by a lower alkyl group, and the lower alkyl esters and pharmaceutically acceptable acid addition salts thereof.
  2. 2. Indane carboxylic acid derivatives as claimed in Claim 1, wherein R represents an acetamido - chlorophenyl group, a methylsulphonyl - phenyl or
    dimethylsulphonyl - phenyl group, a sulphamido - phenyl group a dichloro thienyl group or a methyl - furyl group.
  3. 3. Aminoesters of indane carboxylic acid derivatives represented by the general formula:
    wherein R has the meaning defined in Claim 1 and Am represents a dialkylamino or dialkylaminoalkyl group, and pharmaceutically acceptable acid addition salts of said aminoesters.
  4. 4. Amides of indane carboxylic acid derivatives represented by the general formula:
    wherein R has the meaning defined in Claim 1 and Am' represents a dialkylaminoalkyl group, and pharmaceutically acceptable acid addition salts of said amides.
  5. 5. 5 - (4' - Sulphamidobenzoyl) - indane - 2 - carboxylic acid and the methyl ester thereof.
  6. 6. 5 - (4' - Dimethylaminosulphonyl - benzoyl) - indane - 2 - carboxylic acid.
  7. 7. Ethyl (4' - acetamido - 3' - acetamido - 3' - chloro - benzoyl) - indane 2 - carboxylate.
  8. 8. 5 - [2' - (4",5" - Dichlorothenoyl)] - indane - 2 - carboxylic acid.
  9. 9. 5 - (4' - Methylsulphonyl - benzoyl) - indane - 2 - carboxylic acid.
  10. 10. 5 - [2' - (5" - Methylfuroyl)] - indane - 2 - carboxylic acid.
  11. 11. A pharmaceutical composition comprising a compound as claimed in any one of Claims 1 to 10 and a pharmaceuticàl carrier or excipient therefor.
  12. 12. A composition as claimed in Claim 11, wherein the composition is in a dosage unit form appropriate to the desired mode of administration.
  13. 13. A pharmaceutical composition substantially as described in the foregoing Example 4.
  14. 14. A process for preparing an indane carboxylic acid derivative as claimed in Claim 1, substantially as described in any one of the foregoing Examples 1 to 3.
GB51699/77A 1976-12-14 1977-12-12 Indane carboxylic acid derivatives Expired GB1584298A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7637574A FR2374032A2 (en) 1976-12-14 1976-12-14 NEW CARBOXYLIC ACIDS DERIVED FROM INDANE

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GB1584298A true GB1584298A (en) 1981-02-11

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AT (1) AT355559B (en)
AU (1) AU515268B2 (en)
BE (1) BE861826R (en)
CA (1) CA1088554A (en)
CH (1) CH627728A5 (en)
DD (1) DD133323A6 (en)
DE (1) DE2753315A1 (en)
DK (1) DK144640C (en)
ES (1) ES465056A2 (en)
FR (1) FR2374032A2 (en)
GB (1) GB1584298A (en)
HU (1) HU177226B (en)
IE (1) IE46013B1 (en)
IL (2) IL60598A0 (en)
MX (1) MX4954E (en)
NL (1) NL7713876A (en)
NO (1) NO774285L (en)
SE (1) SE436740B (en)
SU (1) SU799646A3 (en)
ZA (1) ZA777438B (en)

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JP5746334B2 (en) * 2010-06-16 2015-07-08 シマベイ セラピューティクス， インコーポレーテッド GPR120 receptor agonist and use thereof

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JPS4980053A (en) * 1972-12-05 1974-08-02
JPS5838416B2 (en) * 1974-05-31 1983-08-23 武田薬品工業株式会社 Kanjiyoukagobutsunoseizouhou
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ATA892577A (en) 1979-08-15
ZA777438B (en) 1979-05-30
IE46013L (en) 1978-06-14
DK144640B (en) 1982-04-26
FR2374032A2 (en) 1978-07-13
SE436740B (en) 1985-01-21
AT355559B (en) 1980-03-10
BE861826R (en) 1978-06-14
DD133323A6 (en) 1978-12-27
CA1088554A (en) 1980-10-28
MX4954E (en) 1983-01-13
AU515268B2 (en) 1981-03-26
ES465056A2 (en) 1979-01-16
NL7713876A (en) 1978-06-16
HU177226B (en) 1981-08-28
IE46013B1 (en) 1983-01-26
IL60599A0 (en) 1980-09-16
CH627728A5 (en) 1982-01-29
IL60598A0 (en) 1980-09-16
DK144640C (en) 1982-10-04
AU3153077A (en) 1979-06-21
SE7714110L (en) 1978-06-15
DE2753315A1 (en) 1978-06-15
SU799646A3 (en) 1981-01-23
JPS5373548A (en) 1978-06-30
FR2374032B2 (en) 1979-03-30
NO774285L (en) 1978-06-15

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PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee