PL115778B1 - Process for preparing novel 2-pyridyl-and 2-pyrimidylaminobenzoic acids - Google Patents
Process for preparing novel 2-pyridyl-and 2-pyrimidylaminobenzoic acids Download PDFInfo
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- PL115778B1 PL115778B1 PL1978208942A PL20894278A PL115778B1 PL 115778 B1 PL115778 B1 PL 115778B1 PL 1978208942 A PL1978208942 A PL 1978208942A PL 20894278 A PL20894278 A PL 20894278A PL 115778 B1 PL115778 B1 PL 115778B1
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- NNTYAXNEQRSVAQ-UHFFFAOYSA-N 2-(pyrimidin-2-ylamino)benzoic acid Chemical class OC(=O)C1=CC=CC=C1NC1=NC=CC=N1 NNTYAXNEQRSVAQ-UHFFFAOYSA-N 0.000 title claims description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- -1 amino, hydroxylamino Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 6
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 239000002253 acid Substances 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000002211 ultraviolet spectrum Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- JRVHRCWRZAVVSP-UHFFFAOYSA-N 4-(pyridin-2-ylamino)benzene-1,3-dicarboxylic acid Chemical compound OC(=O)C1=CC(C(=O)O)=CC=C1NC1=CC=CC=N1 JRVHRCWRZAVVSP-UHFFFAOYSA-N 0.000 description 1
- DRLIBOWFCYGKBD-UHFFFAOYSA-N 5-methoxycarbonyl-2-(pyridin-2-ylamino)benzoic acid Chemical compound OC(=O)C1=CC(C(=O)OC)=CC=C1NC1=CC=CC=N1 DRLIBOWFCYGKBD-UHFFFAOYSA-N 0.000 description 1
- OQWQZOSTWICYSI-UHFFFAOYSA-N 6-(2-carboxy-4-methylanilino)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC1=CC=C(C(O)=O)C=N1 OQWQZOSTWICYSI-UHFFFAOYSA-N 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000004993 o-toluidines Chemical class 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229940035637 spectrum-4 Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229930195735 unsaturated hydrocarbon Chemical group 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen 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)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarzania no¬ wych kwasów 2^pirydylo- i 2-pirymidyloaniinobenzoeso- wych ewentualnie w postaci soli wewnetrznych lub soli z zasadami, o wartosciowych wlasciwosciach tera¬ peutycznych.Nowym zwigzkom odpowiada wzór 1, w którym A oznacza grupe o wzorze =CH— lub =N—, R., ozna¬ cza atom wodoru, nizszg grupe alkilowa, nizszg grupe alkoksylowg, dokondensowany pierscien benzenowy, lub grupe o wzorze —CO—R4, grupe tetrozolilowg-5 lub grupe cyjanowg w pozycji 4 lub 5, R2 oznacza gru¬ pe o wzorze —CO—R4, tetrazolilowg-5, cyjanowg lub w przypadku gdy R-, oznacza —CO—R4r tetrazolilowg-5 lub cyjanowg w pozycji 4 lub 5, R2 oznacza równiez wodór, nizszg grupe alki Iowg, nizszg grupe alkoksylo¬ wg lub dokondensowany pierscien benzenowy, R3 ozna¬ cza wodór lub nizszg grupe acylowg i R4 oznacza gru¬ pe hydraksylowg, aminowg, hydroksyloaminowg, tetra- zolilo-5-ominowg lub nizszg grupe alkoksylowg.Za nizsze grupy alkilowe, alkoksylowe i acylowe uwa¬ za sie grupy zawierajgce 1—4 atomów wegla, przy czym grupy weglowodorowe mogg byc grupami prosty¬ mi lub rozgalezionymi, np. grupg metylowg, etylowg, propylowg, izopropylowg, n-butylowg, izobulylowg, trze- ciorzedowg butylowg i odpowiednie grupg alkoksylowg, formylowg, acetylowg, propionylowg, butyrylowg.W ramach powyzszych definicji R., i R2 oznaczajg zwlaszcza wodór, dokondensowany pierscien benzeno¬ wy, grupe tetrazolilowg-5 lub karboksylowg. R3 oznacza zwlaszcza wodór. O ile wystepujg sole z zasadami, to 20 25 ^ 2 jako te ostatnie skladniki sluzg przede wszystkim za¬ sady metali alkalicznych lub metali ziem alkalicznych, np. wodorotlenek potasowy lub sodowy lub mocne za¬ sady organiczne, np. nizsze alkiloaminy, etanolooimina, dwu- lub trójetanoloamina.Wedlug wynalazku nowe zwigzki o wzorze 1 wytwa¬ rza sie przez utlenianie zwigzku o wzorze 2, w którym R oznacza grupe przeksztalcaIng w grupe COOH przez utlenianie, a R, i R2 majg wyzej podane znaczenie, zas Acyl oznacza grupe acylowg, i ewentualnie od- szczepianie grupy N-acylowej, i otrzymane sole z za¬ sadami ewentualnie przeprowadza w sole wewnetrzne ewentualnie przeprowadza w sole z zasadami.Jako sole wewnetrzne okresla sie zwigzki, w któ¬ rych grupa aminowa iwystepuje jako jon amoniowy, a grupa karboksylowa w postaci anionu. j Utlenianie przeprowadza sie mocnymi srodkami utleniajgcymi, np. nadmanganianem potasowym w wod¬ nym roztworze, buforowanym siarczanem magnezo¬ wym. Temperatura reakcji wynosi od temperatury po¬ kojowej do temperatury wrzenia mieszaniny reakcyj¬ nej. Dla odszczepi en ia grupy N-acylowej otrzymany zwigzek ewentualnie poddaje sie alkalicznemu mydle¬ niu, np. wodorotlenkiem potasowym.Grupa R moze byc resztg alifatycznego weglowodo¬ ru, w szczególnosci moze stanowic nizszg grupe alki- lowg, jak grupa metylowa liub resztg nienasyconego weglowodoru lub równiez resztg weglowodorowg czes¬ ciowo utleniong, np. resztg weglowodorowg podstawio- 115 778115778 nq grupami hydroksylowymi, ketonowymi, atomami chlo¬ rowca.Produkty wyjsciowe mozna otrzymywac znanymi ja¬ ko takie sposobami, rop. przez reakcje 2-chlorowcopi- rydyny 1'"pochodna o-toluidyny i nastepnie acylawanie.Zwigzki wyjsciowe i zwigzki otrzymywane sposobem wedlug wynalazku nie róznig sie zbyt miedzy sobq dzialaniem farmakologicznym. Róznig sie jednak znacz¬ nie swg budowa chemiczna. Z róznicy strukturalnej wy¬ nikaja duze. korzysci lecznicze, gdyz zwigzki o wzorze ogólnym 1 sg bardzo trwale w postaci fizjologicznie do¬ puszczalnych soli, w szczególnosci soli metali alka¬ licznych. Zawierajace te zwigzki lub ich sole preparaty farmaceutyczne sg znacznie bardziej stabilne co w dzie¬ dzinie leków ma ogromne znaczenie.Otrzymywane sposobem wedlug wynalazku nowe zwigzki majg zastosowanie terapeutyczne lub moga sluzyc jako produkty posrednie w wytwarzaniu leków.Nalezy podniesc tu ich dzialanie przeciwalergiczne.Moze ono byc wykorzystane w profilaktyce i do trak¬ towania chorób alergicznych, takich jak astma lub go¬ raczka sienna, conjunotivitis, pokrzywka, egzemy, uczu¬ leniowe zapalenie skóry. Nowe zwigzki wykazuja przy tym dzialanie rozluzniajace miesnie (rozszerzajace oskrzela) i rozszerzajgce naczynia.Przy najwazniejszym stosowaniu, w profilaktyce astmy, nalezy wymienic jako znaczne korzysci iw stosunku do produktu handlowego kwasu kremoglicynowego, dluzszy czas dzialania i przede wszystkim aktywnosc przy podawaniu doustnym.Otrzymywane sposobem wedlug wynalazku zwigzki przerabia sie w znany sposób na galenowe formy uzyt¬ kowe z substancjami pomocniczymi i nosnikami, np. na kapsulki, tabletki, drazetki, roztwory zawiesiny do sto¬ sowania doustnego, na aerozole do podawania pluc¬ nego, na sterylne izotoniczne wodne roztwory do sto¬ sowania pozajelitowego i na kremy, imascie, lotiony, emulsje lub spray'e do stosowania lokalnego.Dawka jednostkowa zalezy od wskazan, np. jakosci stanu alergicznego. Na ogól dawka na 1 kg ciezaru ciala wynosi przy stosowaniu do pluc od okolo 20— —500 ug, przy stosowaniu dozylnym od okolo 0,2 do 10 mg, przy doustnym stosowaniu od okolo 1 do 50 mg.Do nosa lub do oka stosuje sie okolo 0,5 do 25 mg.Nastepujace przyklady wyjasniaja sposób wytwarza¬ nia wedlug wynalazku. Widma w nadfiolecie wykona¬ no fotometrem spektralnym (Spektralfotameter DMR 21 firmy Zeiss, Oberkochen). Kazdorazowo dokladnie od¬ wazano 10—20 mg substancji, a w przypadku sub- stancjii oznaczonych za pomoca x rozpuszczono je wzglednie rozcienczono 10 ml sulfbtlenku dwumetylu rozpuszczonego w 0,01 n lugu sodowym. Wybrane dlugofalowe pasma absorpcyjne. Absorpcje w maksy- muim zostaly podane jako X max/nm z nalezytym molowym logarytmicznym wspólczynnikiem ekstynkcji jako log 8.Przyklad I. Sól dwupotasowa kwasu 4-/2-pkydy- loamino/-izofta!owego o wzorze 3. 4,8 g N-/2-pirydylo/-2,4-dwumetyloacetanilidu (tempe¬ ratura topnienia 46—50°C), wytworzonego z 2-chloropi- rydyny i 2,4-dwumetyloaniilmy w temperaturze 160— —170°C i nastepnie acetylawame bezwodnikiem octo¬ wym, rozpuszcza sie razem z 2,4 g siarczanu magne¬ zu w wodzie. Do ogrzanego do temperatury 30°C roz¬ tworu dodaje sie porcjami 12,64 g nadmanganianu po- 10 15 20 tasowego. Miesza sie przez 2 godziny w temperaturze 80—90°C na lazni wodnej, powstaly dwutlenek man¬ ganu odciaga sie na gorgco i przemywa woda. Po zatezeniu roztworu do objetosci 50 ml rozciencza sie 50 ml etanolu \ odciaga wytracony siarczan potaso¬ wy. AlkoholowoHWodny roztwór zateza sie w prózni, po¬ zostalosc doprowadza sie ukladem etanol/eter do kry¬ stalizacji. 1 g tak otrzymanej soli potasowej kwasu N-acetylo- N-/2Hpirydylo/-4-amino-izoftalowego ogrzewa sie do wrzenia przez 2 godziny z 0,4 g wodorotlenku pota¬ sowego w 10 ml wody, pod chlodnicg zwrotna i po¬ zostalosc rozciera sie z etanolem/eterem. Sól potaso¬ wa kwasu 4-/2-pirydyloamino/-izoftalowego (scharakte¬ ryzowana widmem NMR) wykrystalizowuje.Widmo w nadfiolecie X max 290 nm 332 nm log. e 4,21 4,52 Analogicznie otrzymuje sie nastepujace zwigzki: Sól sodowa kwasu 4-/2^pirydyloamino/-izoftalowego o wzorze 4.Analiza: C13H8N204Na2 X 2 H20 wyliczono: znaleziono: C % H o/0 N o/0 46,15 3,55 8,28 46,04 3,34 8', 15 X max 288 nm log 8 4,18 H20 % 10,65 11,16 328 nm 4,30 wyliczono: znaleziono: Widmo w nadfiolecie C'% 41,05 41,98 X max log e H % 3,68 3,54 290 nm 4,24 N% 22,10 22,18 317 nm 4,27 oraz zwigzki podane w tabeli (jako sole sodowe, po¬ dano przy tym dane widma w nadfiolecie soli Na): Tabela 25 Widmo w nadfiolecie Sól dwusodowg kwasu 2-/2-pirydyloomino/-5-/1H-te- trazoJilo-5Menzoesowego o wzorze 5.Analiza: C13H8N602Na2 X 3 H20 30 35 40 45 50 55 60 65 Zwigzek 1 ester monometylowy kwasu 4-/2-pirydyloami- no/^izoftalowego kwas 4-/2-C hinolinylo- amino/-izoftaldwy kwas 6-/2-karboksy-4- -metylo^fenyloamiino/- -Nikotynowy 1-monoamdi kwasu 4- -/2-pirydyloamino/-izo- ftalowego kwas 5-cyjano-2-/2- -pirydyloomino/-benzo- esowy kwas 4-/2^pirydyloami- no/- 1-mono-hydroksamowy kwas 2-/2Hpirydyloomi- noMereftalowy Wzór strukturalny 2 wzór 6 wzór 7 wzór 8 wzór 9 wzór 10 wzór 11 wzór 12 Widmo w nadfiolecie X max (nm) 3 238 326 292 355 320 288 326 295 324 292 324 252 278 log s 4 4,18 4,40 4,32 4,34 4,25 4,13 4,37 4,16 4,39 4,20 4,26 1 4,17 4,14115 778 1 kwas 6-/2-karboksy-4- ¦^metoksyfenyloamino/- -nikotynowy kwas 6-/3^ka,rboksy-2-v -nafty I oamino/-nikoly- nowy kwas 4-/2-pirymidylo- Gmino/-izoftalowy kwas 4-/5-amino-2- -pirydyloamino-izofta- Jowy kwas 4-/5^ocetamido- 2-pirydyloamino/-tizo- ftalowy 4-/2-p;rydyioamino/- Hzoftalowy-mono-N- -/1 hMetrazolHo-5-karbo- ksyamid kwas 6-/2-karboksyfe- nylo-aimino-nikotynowy kwas N-acetylo-N-/2- npirydyloM-aminoizo- ftalowy '""" 2 wzór 13 wzór 14 wzór 15 wzór 16 wzór 17 wzór 18 wzór 19 wzór 20 3 310 275 326 288 325 298 338 298 335 290 330 325 265 4 4r21 4,32 4,32 4,23 4,32 4,31 4,19 4,25 4,30 4,17 4,43 4,30 3£6 10 15 20 25 Zastrzezenie patentowe Sposób wytwarzania nowych kwasów 2-pirydylo- i 2- -pirymidyloaminobenzoesowych o wzorze 1, w którym A oznacza grupe o wzorze =CH— lub =N—, Rj ozna¬ cza wodór, nizszg grupe alkilawg, nizszg grupe alko¬ ksylowg, dokondensowany pierscien benzenowy, lub grupe o wzorze —CO^R4l grupe tetrazolilowg-5, cy¬ janowg w pozycji 4 lub 5, R2 oznacza grupe o wzorze —CO—R4, grupe tetrazolilawg-5, cyjanowg lub, w przy¬ padku gdy Rt oznacza grupe —CO—R4, tetrazolilowg-5 lub cyjanowg lub w przypadku, gdy R<\ oznacza —CO— —R4, grupe tetrazoliilowq-5 lub cyjanowg w pozycji 4 lub 5, R2 oznacza równiez wodór, nizszg grupe alki¬ lowa, nizszg grupe alkoksylowg lub dokondensowany pierscien benzenowy, R3 oznacza wodór lub grupe acy- lowg i R4 oznacza grupe hydroksylowe, aminowg, hy- droksyloaminowg, tetrazolilo-5-aminowg lub nizszg gru¬ pe alkoksylowg, ewentualnie w postaci wewnetrznych soli lub soli z zasadowymi skladnikami, znamienny tym, ze zwigzek o wzorze 2, w którym R oznacza grupe przeksztalcaIng w grupe COOH przez utlenianie, R^ i R2 majg wyzej podane znaczenie, utlenia sie i ewen¬ tualnie odszczepia grupe N-acylowg i otrzymane sole z zasadami ewentualnie przeprowadza w sole wewnetrz¬ ne, sole wewnetrzne ewentualnie przeksztalca w sole z zasadami Rf COOH fi C02Na ^-NH^O-CJ^I Na x 2hLO HOOC ^ COOH NH XX WZÓR I r; ^ .JL„W:Ro X: "AcyL WZÓR 2 C02K {3~m~^-QD2^ WZ0R 4 C02Na V-. N_N WZÓR 7 ^-NH-^-(j| x 3H20 CH3. . COOH . COOH N"N Na 'XiWHxr WZÓR 5 H00C COOCHo l^A NH JU • WZÓR 8 O II HOOC C-NHC Cl mXX WZÓR 3 WZÓR 6 WZÓR 9115 778 HOOC . CN NH CH3o .COOH ..^ COOH XK nh XT WZÓR 10 O HOOC . C-NH-OH NH Ol. NH XT WZÓR 13 COOH _ COOH N^ NH WZÓR 11 WZÓR 14 HOOC NH "~^^COOH nuu^ Ck mm Xl HOOC COOH Sf^ NH ^^ WZÓR 12 WZÓR 15 H2N^ ^ H00c- ~ COOH NH Xr 0- II ch3-c-nh WZÓR 16 HOOC ^ COOH NH XT HOOC-f^N HOOC NH WZÓR 19 WZOR 17 O II N_m .., HOOC C-NH^ 11 a m xx r HOOC N OC-CH3 WZOR 20 COOH WZOR 18 LDA - Zaklad 2 - zam. 194/82 - 85 egz.Cena 100 zl PL PL PL PL PL PL PL PL PL PL
Claims (1)
1. Zastrzezenie patentowe Sposób wytwarzania nowych kwasów 2-pirydylo- i 2- -pirymidyloaminobenzoesowych o wzorze 1, w którym A oznacza grupe o wzorze =CH— lub =N—, Rj ozna¬ cza wodór, nizszg grupe alkilawg, nizszg grupe alko¬ ksylowg, dokondensowany pierscien benzenowy, lub grupe o wzorze —CO^R4l grupe tetrazolilowg-5, cy¬ janowg w pozycji 4 lub 5, R2 oznacza grupe o wzorze —CO—R4, grupe tetrazolilawg-5, cyjanowg lub, w przy¬ padku gdy Rt oznacza grupe —CO—R4, tetrazolilowg-5 lub cyjanowg lub w przypadku, gdy R<\ oznacza —CO— —R4, grupe tetrazoliilowq-5 lub cyjanowg w pozycji 4 lub 5, R2 oznacza równiez wodór, nizszg grupe alki¬ lowa, nizszg grupe alkoksylowg lub dokondensowany pierscien benzenowy, R3 oznacza wodór lub grupe acy- lowg i R4 oznacza grupe hydroksylowe, aminowg, hy- droksyloaminowg, tetrazolilo-5-aminowg lub nizszg gru¬ pe alkoksylowg, ewentualnie w postaci wewnetrznych soli lub soli z zasadowymi skladnikami, znamienny tym, ze zwigzek o wzorze 2, w którym R oznacza grupe przeksztalcaIng w grupe COOH przez utlenianie, R^ i R2 majg wyzej podane znaczenie, utlenia sie i ewen¬ tualnie odszczepia grupe N-acylowg i otrzymane sole z zasadami ewentualnie przeprowadza w sole wewnetrz¬ ne, sole wewnetrzne ewentualnie przeksztalca w sole z zasadami Rf COOH fi C02Na ^-NH^O-CJ^I Na x 2hLO HOOC ^ COOH NH XX WZÓR I r; ^ .JL„W:Ro X: "AcyL WZÓR 2 C02K {3~m~^-QD2^ WZ0R 4 C02Na V-. N_N WZÓR 7 ^-NH-^-(j| x 3H20 CH3. . COOH . COOH N"N Na 'XiWHxr WZÓR 5 H00C COOCHo l^A NH JU • WZÓR 8 O II HOOC C-NHC Cl mXX WZÓR 3 WZÓR 6 WZÓR 9115 778 HOOC . CN NH CH3o .COOH ..^ COOH XK nh XT WZÓR 10 O HOOC . C-NH-OH NH Ol. NH XT WZÓR 13 COOH _ COOH N^ NH WZÓR 11 WZÓR 14 HOOC NH "~^^COOH nuu^ Ck mm Xl HOOC COOH Sf^ NH ^^ WZÓR 12 WZÓR 15 H2N^ ^ H00c- ~ COOH NH Xr 0- II ch3-c-nh WZÓR 16 HOOC ^ COOH NH XT HOOC-f^N HOOC NH WZÓR 19 WZOR 17 O II N_m .., HOOC C-NH^ 11 a m xx r HOOC N OC-CH3 WZOR 20 COOH WZOR 18 LDA - Zaklad 2 - zam. 194/82 - 85 egz. Cena 100 zl PL PL PL PL PL PL PL PL PL PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772735919 DE2735919A1 (de) | 1977-08-10 | 1977-08-10 | Neue 2-pyridyl- und 2-pyrimidylaminobenzoesaeuren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL208942A1 PL208942A1 (pl) | 1979-12-03 |
| PL115778B1 true PL115778B1 (en) | 1981-04-30 |
Family
ID=6016013
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1978208942A PL115778B1 (en) | 1977-08-10 | 1978-08-09 | Process for preparing novel 2-pyridyl-and 2-pyrimidylaminobenzoic acids |
| PL1978215270A PL115889B1 (en) | 1977-08-10 | 1978-08-09 | Process for manufacturing novel 2-pyridyl-and 2-pyrimidinylaminobenzoic acids |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1978215270A PL115889B1 (en) | 1977-08-10 | 1978-08-09 | Process for manufacturing novel 2-pyridyl-and 2-pyrimidinylaminobenzoic acids |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4241068A (pl) |
| JP (1) | JPS5430177A (pl) |
| AT (1) | AT370415B (pl) |
| AU (1) | AU520240B2 (pl) |
| BE (1) | BE869640A (pl) |
| BG (1) | BG30472A1 (pl) |
| CA (1) | CA1111037A (pl) |
| CH (1) | CH649289A5 (pl) |
| CS (1) | CS202506B2 (pl) |
| DD (1) | DD140351A5 (pl) |
| DE (1) | DE2735919A1 (pl) |
| DK (1) | DK148019C (pl) |
| ES (5) | ES472143A1 (pl) |
| FI (1) | FI71555C (pl) |
| FR (1) | FR2400017A1 (pl) |
| GB (1) | GB2002764B (pl) |
| GR (1) | GR65024B (pl) |
| HU (1) | HU179933B (pl) |
| IE (1) | IE47228B1 (pl) |
| IT (1) | IT1107960B (pl) |
| LU (1) | LU80094A1 (pl) |
| MX (1) | MX5672E (pl) |
| NL (1) | NL7808319A (pl) |
| NO (1) | NO152605C (pl) |
| NZ (1) | NZ188101A (pl) |
| PH (1) | PH19117A (pl) |
| PL (2) | PL115778B1 (pl) |
| PT (1) | PT68407A (pl) |
| SE (1) | SE444170B (pl) |
| SU (2) | SU735168A3 (pl) |
| YU (1) | YU40832B (pl) |
| ZA (1) | ZA784501B (pl) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3100516A1 (de) * | 1981-01-10 | 1982-08-12 | C.H. Boehringer Sohn, 6507 Ingelheim | Pyridylaminobenzoesaeuren, ihre herstellung und verwendung |
| FR2533567A1 (fr) * | 1982-09-23 | 1984-03-30 | Ki I Farmakologii | 2-(orthocarboxyphenylamino)-6h-pyrimido (2,1-b)-quinazolone-6 et ses derives, leur procede de preparation et leur application therapeutique |
| US4610991A (en) * | 1983-04-18 | 1986-09-09 | Sterling Drug Inc. | Antihypertensive pyridylaminobenzamide compounds |
| JPS60100559A (ja) * | 1983-11-05 | 1985-06-04 | Morishita Seiyaku Kk | ２−アニリノ−１，６−ジヒドロ−６−オキソ−５−ピリミジンカルボン酸誘導体，その製法及び該化合物を含有する抗アレルギ−剤 |
| US4584379A (en) * | 1985-01-22 | 1986-04-22 | Merrell Dow Pharmaceuticals Inc. | Isoquinoline thromboxane synthetase inhibitors |
| ATE68789T1 (de) * | 1985-10-16 | 1991-11-15 | Merck Frosst Canada Inc | 2-substituierte chinoline. |
| GB9615950D0 (en) * | 1996-07-30 | 1996-09-11 | Univ Warwick | Variable reluctance machines |
| US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1064259A (en) * | 1963-12-19 | 1967-04-05 | Union Pharma Scient Appl | New derivatives of 2-anilino-nicotinic acid and process for their preparation |
| GB1162287A (en) * | 1967-11-07 | 1969-08-20 | Union Pharma Scient Appl | New Salts of 2-Anilino-Nicotinic Acids |
| GB1264798A (pl) * | 1968-07-10 | 1972-02-23 | ||
| ES416847A1 (es) * | 1973-07-12 | 1976-03-01 | Hermes Sa Lab | Procedimiento para la obtencion de derivados del acido ni- cotinico. |
-
1977
- 1977-08-10 DE DE19772735919 patent/DE2735919A1/de active Granted
-
1978
- 1978-06-27 FI FI782039A patent/FI71555C/fi not_active IP Right Cessation
- 1978-07-07 GR GR56729A patent/GR65024B/el unknown
- 1978-07-28 AT AT0549278A patent/AT370415B/de not_active IP Right Cessation
- 1978-07-28 ES ES472143A patent/ES472143A1/es not_active Expired
- 1978-07-31 PH PH21447A patent/PH19117A/en unknown
- 1978-08-07 MX MX787292U patent/MX5672E/es unknown
- 1978-08-07 CH CH8381/78A patent/CH649289A5/de not_active IP Right Cessation
- 1978-08-08 SU SU782646404A patent/SU735168A3/ru active
- 1978-08-08 BG BG7840623A patent/BG30472A1/xx unknown
- 1978-08-08 LU LU80094A patent/LU80094A1/de unknown
- 1978-08-08 IT IT50642/78A patent/IT1107960B/it active
- 1978-08-08 DD DD78207180A patent/DD140351A5/de unknown
- 1978-08-09 HU HU78BO1727A patent/HU179933B/hu not_active IP Right Cessation
- 1978-08-09 SE SE7808530A patent/SE444170B/sv not_active IP Right Cessation
- 1978-08-09 IE IE1618/78A patent/IE47228B1/en unknown
- 1978-08-09 DK DK351978A patent/DK148019C/da not_active IP Right Cessation
- 1978-08-09 GB GB7832731A patent/GB2002764B/en not_active Expired
- 1978-08-09 ZA ZA784501A patent/ZA784501B/xx unknown
- 1978-08-09 JP JP9626278A patent/JPS5430177A/ja active Granted
- 1978-08-09 CS CS785205A patent/CS202506B2/cs unknown
- 1978-08-09 NO NO782707A patent/NO152605C/no unknown
- 1978-08-09 AU AU38772/78A patent/AU520240B2/en not_active Expired
- 1978-08-09 PL PL1978208942A patent/PL115778B1/pl unknown
- 1978-08-09 PT PT68407A patent/PT68407A/pt unknown
- 1978-08-09 NZ NZ188101A patent/NZ188101A/xx unknown
- 1978-08-09 PL PL1978215270A patent/PL115889B1/pl unknown
- 1978-08-09 CA CA308,978A patent/CA1111037A/en not_active Expired
- 1978-08-09 YU YU1916/78A patent/YU40832B/xx unknown
- 1978-08-09 BE BE78189801A patent/BE869640A/xx not_active IP Right Cessation
- 1978-08-09 NL NL787808319A patent/NL7808319A/xx not_active Application Discontinuation
- 1978-08-10 FR FR7823617A patent/FR2400017A1/fr active Granted
- 1978-11-28 ES ES475456A patent/ES475456A1/es not_active Expired
- 1978-11-28 ES ES475457A patent/ES475457A1/es not_active Expired
-
1979
- 1979-05-16 ES ES480623A patent/ES480623A1/es not_active Expired
- 1979-05-16 ES ES480622A patent/ES480622A1/es not_active Expired
- 1979-05-21 SU SU792765447A patent/SU886743A3/ru active
- 1979-08-07 US US06/064,355 patent/US4241068A/en not_active Expired - Lifetime
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