DK166127B - Estere af pyridin-2,4- og -2,5-dicarboxylsyre til anvendelse som laegemidler, samt laegemidler indeholdende disse estere - Google Patents
Estere af pyridin-2,4- og -2,5-dicarboxylsyre til anvendelse som laegemidler, samt laegemidler indeholdende disse estere Download PDFInfo
- Publication number
- DK166127B DK166127B DK397785A DK397785A DK166127B DK 166127 B DK166127 B DK 166127B DK 397785 A DK397785 A DK 397785A DK 397785 A DK397785 A DK 397785A DK 166127 B DK166127 B DK 166127B
- Authority
- DK
- Denmark
- Prior art keywords
- esters
- pyridine
- collagen
- dicarboxylic acid
- pharmaceuticals
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 9
- 150000002148 esters Chemical class 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical class OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 abstract description 11
- 108010035532 Collagen Proteins 0.000 abstract description 11
- 229920001436 collagen Polymers 0.000 abstract description 11
- 239000003112 inhibitor Substances 0.000 abstract description 10
- 102000004079 Prolyl Hydroxylases Human genes 0.000 abstract description 7
- 108010043005 Prolyl Hydroxylases Proteins 0.000 abstract description 7
- 102000008490 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Human genes 0.000 abstract description 3
- 108010020504 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Proteins 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 229960003444 immunosuppressant agent Drugs 0.000 abstract description 3
- 239000003018 immunosuppressive agent Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
- 230000004060 metabolic process Effects 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- 230000036570 collagen biosynthesis Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229960002591 hydroxyproline Drugs 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- CCMLIFHRMDXEBM-UHFFFAOYSA-N 2-phenyl-1,3-thiazol-4-ol Chemical compound OC1=CSC(C=2C=CC=CC=2)=N1 CCMLIFHRMDXEBM-UHFFFAOYSA-N 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 208000024781 Immune Complex disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000007691 collagen metabolic process Effects 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
i
DK 166127 B
Opfindelsen angår pyridindicarboxylsyreestere med den almene formel
R2OCO
5 (I) ^N^COOR1 hvor R1 og R2, der er ens eller forskellige, betyder alkyl 10 med 1-6 carbonatomer, og hvor gruppen R2OCO er bundet i 4-eller 5-stilling i pyridinringen, til anvendelse som lægemidler, især til inhibering af prolin- og lysinhydroxylase eller til anvendelse som fibrosuppressivum og immunsuppres-sivum. Opfindelsen angår også lægemidler, der indeholder en 15 forbindelse med formlen (I) , evt. sammen med acceptable farmaceutiske bærestoffer.
Ifølge den foreliggende opfindelse foretrækkes der sådanne forbindelser med formlen (I), hvor begge grupperne R1 og R2 betyder alkylgrupper med 1-3 carbonatomer, især 20 ethyl.
Fra EP-B1 nr. 0033151 (US-patentskrift nr. 4.457.
936) er det kendt, at carboxylsyrer af hydroxyphenylthiazol og derivater deraf påvirker kollagenstofskiftet. Disse forbindelser virker som inhibitorer af prolin- og lysinhydroxy-25 laser og bevirker således en meget selektiv hæmning af kolla-genbiosyntesen ved at påvirke de kollagenspecifikke hydroxy-leringsreaktioner. Under dette forløb hydroxyleres proteinbundet prolin eller lysin af enzymerne prolin- og lysinhydro-xylase. Såfremt denne reaktion hindres af inhibitorer, opstår 30 der et ikke-funktionsdygtigt, underhydroxyleret kollagenmole-kyle, der kun i ringe mængde kan afgives af cellen i det ekstracellulære rum. Desuden kan det underhydroxylerede kollagen ikke indbygges i kollagenmatrixen og nedbrydes meget let proteolytisk. Som en følge af disse virkninger 35 forringes tilsammen mængden af det ekstracellulært af lej rede kollagen.
DK 166127 B
2
Det er desuden kendt, at inhiberingen af prolinhydro-xylasen med kendte inhibitorer som α,α'-dipyridyl fører til en hæmning af Clg-biosyntesen af makrophager (jfr. W. Muller et al., FEBS Lett. 90 (1978) 218? Immunobiology 155 5 (1978) 47) . Dette udelukker den klassiske komplementaktive ring. Inhibitorer af prolinhydroxylase virker derfor også som immunsuppressiva, f.eks. ved immunkomplekssygdomme.
Det er kendt, at prolinhydroxylase hæmmes effektivt af pyridin-2,4- og -2,5-dicarboxylsyre (jfr. K. Majamaa et 10 al., Eur. J. Biochem. 138 (1984) 239-245). Disse forbindelser er ganske vist kun virksomme som hæmningsstoffer i cellekulturen i meget høje koncentrationer (jfr. V. Gunzler et al., Collagen and Related Research 3 (1983) 71). Overraskende nok har det nu vist sig, at estrene af disse forbindelser 15 er væsentlig mere højaktive hæmningsstoffer af kollagen-biosyntesen i celle- og organkulturer.
Stoffernes hæmmende virkning på kollagenbiosyntesen kan påvises i cellekulturen med fibroblaster eller andre kollagen-syntetiserende celler eller i organkulturer fra 20 kalvarier (embryonale kyllingehjerneskaller) eller andre kollagen-producerende organer.
Den hæmmende virkning på Clg-biosyntesen kan i cellekulturer bestemmes med makrophager (jfr. Muller et al., FEBS Lett., jfr. ovenfor).
25 Forbindelserne med formlen (I) kan anvendes som medi kamenter i form af farmaceutiske præparater, der indeholder disse eventuelt sammen med acceptable farmaceutiske bærestoffer. Forbindelserne kan anvendes som lægemidler, f.eks. i form af farmaceutiske præparater, der indeholder disse for-30 bindeiser i blanding med et til en enteral, perkutan eller parenteral applikation egnet farmaceutisk, organisk eller uorganisk bæremateriale, såsom vand, gummi arabicum, gelatine, mælkesukker, stivelse, magnesiumstearat, talkum, vegetabilske olier, polyalkylenglycoler, vaseline osv.
35 De farmaceutiske præparater kan foreligge i fast form, f.eks. som tabletter, dragées, suppositorier eller
DK 166127 B
3 kapsler, i halvfast form, f.eks. som salver, eller i flydende form, f.eks. som opløsninger, suspensioner eller emulsioner.
De er eventuelt steriliseret og/eller indeholder hjælpestoffer, såsom konserveringsmidler, stabiliseringsmidler, fugte-5 midler eller emulgeringsmidler, salte til ændring af det osmotiske tryk eller puffere. De kan også indeholde andre terapeutisk virksomme stoffer.
Forbindelser med formlen (I) kan tjene som insektfor-svarsmidler (jfr. US-patentskrift nr. 2.852.519) eller ud-10 gangsmaterialer til baktericider (jfr. US-patentskrift nr. 2.809.146). Deres fremstilling kan ske ifølge litteraturkendte metoder, f.eks. ifølge fremgangsmåden beskrevet i US-patentskrift nr. 2.852.519.
I det følgende er beskrevet bestemmelsen af den hæra-15 mende virkning på reaktionen prolin -* hydroxyprolin, som katalyseres af enzymet prolinhydroxylase.
a) Væv af EHS-sarkom-tumor, der producerer en basal-membranagtig ekstracellulær matrix og specielt type IV-kol-lagen (jfr. Erkin et al., Exp. Med. 145 (1977) 204-220), 20 inkuberes analogt med metoden ifølge K. Tryggvason et al. (Biochemistry 19 (1989) 1248-1289) i nærværelse af 14C-prolin og af inhibitorer i forskellig koncentration. Efter at inkubationen er standset, homogeniseres vævet og ekstraheres med fortyndet eddikesyre. Efter NaCl-fældning hydrolyseres 25 det ekstraherede kollagen med 6 M HC1, og forholdet mellem 14C-prolin og 14C-hydroxyprolin bestemmes.
b) Isolerede kalvarier inkuberes analogt med fremgangsmåden beskrevet af B. Peterkovsky og R. DiBlasio (Anal. Biochem. 66 (1975) 279-286) i nærværelse af U-14C-prolin og 30 inhibitorer. Efter at inkubationen er standset, homogeniseres kalvarierne, og kollagenet ekstraheres med fortyndet eddikesyre. Efter hydrolyse af ekstrakten med 6 M HC1 bestemmes forholdet mellem ^-4C-prolin og -*-4C-hydroxyprolin.
DK 166127 B
4
Der fås følgende resultater bestemt ved metode b) som er et udtryk for hæmningen af kollagenbiosyntesen.
Inhibitor med formlen (I): 5 12 2 R = R COOR 's position Kone., μΜ Hæmning, % H 4 670 50 C2H5 4 3 50 H 5 2100 50 C2H5 5 90 50
Claims (5)
1. Pyridindicarboxylsyreestere med den almene formel R2OCO 5 iPi (1) ^^COOR1 hvor R1 og R2, der er ens eller forskellige, betyder alkyl med 1-6 carbonatomer, og hvor gruppen R2OCO er bundet i 4-10 eller 5-stilling i pyridinringen, til anvendelse som lægemidler.
2. Forbindelser ifølge krav 1, kendetegnet ved, at R1 og R2 betyder alkylgrupper med 1-3 carbonatomer.
3. Forbindelser ifølge krav 1 og 2, kendete g-15 net ved, at R1 og R2 betyder ethyl.
4. Lægemiddel, kendetegnet ved, at det indeholder en forbindelse ifølge krav 1.
5. Lægemiddel, kendetegnet ved, at det indeholder en forbindelse ifølge krav 1 sammen med acceptable 20 farmaceutiske bærestoffer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843432094 DE3432094A1 (de) | 1984-08-31 | 1984-08-31 | Ester der pyridin-2,4- und -2,5- dicarbonsaeure als arzneimittel zur inhibierung der prolin- und lysinhydroxylase |
| DE3432094 | 1984-08-31 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK397785D0 DK397785D0 (da) | 1985-08-30 |
| DK397785A DK397785A (da) | 1986-03-01 |
| DK166127B true DK166127B (da) | 1993-03-15 |
| DK166127C DK166127C (da) | 1993-08-09 |
Family
ID=6244394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK397785A DK166127C (da) | 1984-08-31 | 1985-08-30 | Estere af pyridin-2,4- og -2,5-dicarboxylsyre til anvendelse som laegemidler, samt laegemidler indeholdende disse estere |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4717727A (da) |
| EP (1) | EP0176741B1 (da) |
| JP (1) | JPH0641412B2 (da) |
| AT (1) | ATE38222T1 (da) |
| AU (1) | AU588826B2 (da) |
| CA (1) | CA1246456A (da) |
| DE (2) | DE3432094A1 (da) |
| DK (1) | DK166127C (da) |
| ES (1) | ES8609255A1 (da) |
| GR (1) | GR852098B (da) |
| IE (1) | IE58599B1 (da) |
| PT (1) | PT81058B (da) |
| ZA (1) | ZA856646B (da) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5238948A (en) * | 1987-02-10 | 1993-08-24 | Hoechst Aktiengesellschaft | Pyridine-2,4- and -2,5-dicarboxylic acid derivatives and medicaments based on these compounds |
| DE3703963A1 (de) * | 1987-02-10 | 1988-08-18 | Hoechst Ag | Pyridin-2,4- und 2,,5-dicarbonsaeure-derivate, verfahren zu ihrer herstellung, verwendung derselben, sowie arzneimittel auf basis dieser verbindungen |
| US5512586A (en) * | 1987-02-10 | 1996-04-30 | Hoechst Aktiengesellschaft | Medicaments based on pyridine-2,4- and 2,5-dicarboxylic acid amides |
| DE3703959A1 (de) * | 1987-02-10 | 1988-08-18 | Hoechst Ag | Pyridin-2,4- und 2,5-dicarbonsaeureamide, verfahren zu ihrer herstellung, verwendung derselben sowie arzneimittel auf basis dieser verbindungen |
| GB8702890D0 (en) * | 1987-02-10 | 1987-03-18 | Zyma Sa | Heterocyclic compounds |
| DE3703962A1 (de) * | 1987-02-10 | 1988-08-18 | Hoechst Ag | Pyridin-2,4- und 2,5-dicarbonsaeure-derivate, verfahren zu ihrer herstellung, verwendung derselben sowie arzneimittel auf basis dieser verbindungen |
| DE3707429A1 (de) * | 1987-03-07 | 1988-09-15 | Hoechst Ag | Substituierte pyridin-2,4-dicarbonsaeure-derivate, verfahren zu ihrer herstellung, verwendung derselben sowie arzneimittel auf basis dieser verbindungen |
| US5124392A (en) * | 1988-10-03 | 1992-06-23 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment to prevent and treat corneal scar formation produced by laser irradiation |
| US4939135A (en) * | 1988-10-03 | 1990-07-03 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment to prevent and treat corneal scar formation produced by laser irradiation |
| US5271939A (en) * | 1988-10-03 | 1993-12-21 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment to prevent and treat corneal scar formation produced by laser irradiation |
| US5360611A (en) * | 1988-10-03 | 1994-11-01 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment of the cornea following ultraviolet laser irradiation |
| DE3924093A1 (de) | 1989-07-20 | 1991-02-07 | Hoechst Ag | N,n'-bis(alkoxy-alkyl)-pyridin-2,4-dicarbonsaeurediamide, verfahren zu deren herstellung sowie deren verwendung |
| DE3930696A1 (de) * | 1989-09-14 | 1991-03-28 | Hoechst Ag | Gallensaeurederivate, verfahren zu ihrer herstellung, verwendung als arzneimittel |
| DE3938805A1 (de) * | 1989-11-23 | 1991-05-29 | Hoechst Ag | Pyridin-2,4- und 2,5-dicarbonsaeurediamide, verfahren zu deren herstellung sowie deren verwendung |
| ZA91291B (en) * | 1990-01-16 | 1991-09-25 | Hoechst Ag | Di(nitroxyalkyl)amides of pyridine-2,4-and-2,5-dicarboxylic acids,a process for the preparation thereof,and the use thereof |
| DE4020570A1 (de) | 1990-06-28 | 1992-01-02 | Hoechst Ag | 2,4- und 2,5-substituierte pyridin-n-oxide, verfahren zu deren herstellung sowie deren verwendung |
| DE4030999A1 (de) * | 1990-10-01 | 1992-04-09 | Hoechst Ag | 4- oder 5-substituierte pyridin-2-carbonsaeuren, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
| YU9492A (sh) * | 1991-02-05 | 1995-03-27 | Hoechst Ag. | 2,4- i 2,5-bis-tetrazolilni piridini i postupak za njihovo dobijanje |
| TW352384B (en) * | 1992-03-24 | 1999-02-11 | Hoechst Ag | Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals |
| DE4233124A1 (de) * | 1992-10-02 | 1994-04-07 | Hoechst Ag | Acylsulfonamido- und Sulfonamidopyridin-2-carbonsäureester sowie ihre Pyridin-N-oxide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US5624893A (en) * | 1993-10-14 | 1997-04-29 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment of the cornea following laser irradiation |
| EP0878480A1 (en) * | 1997-05-14 | 1998-11-18 | H.W. Prof. Dr. Müller | A method for the improvement of neuronal regeneration |
| EP1268639A1 (en) * | 2000-02-11 | 2003-01-02 | Huntsman International Llc | Fatty acid and polyolefin wax release agent |
| US7598278B2 (en) * | 2002-04-11 | 2009-10-06 | L'oreal | Administration of pyridinedicarboxylic acid compounds for stimulating or inducing the growth of human keratinous fibers and/or arresting their loss |
| WO2005020977A1 (en) * | 2003-08-21 | 2005-03-10 | Wisconsin Alumni Research Foundation | Alpha-ketoglutarate potentiators of insulin secretion |
| FR2987742B1 (fr) | 2012-03-09 | 2014-09-26 | Oreal | Procede de traitement pour la protection et la reparation des fibres keratiniques mettant en œuvre des polysaccharides oxydes |
| FR3010312B1 (fr) * | 2013-09-12 | 2015-09-11 | Oreal | Procede de traitement des fibres keratiniques avec un polysaccharide et un compose d'acide pyridine dicarboxylique |
| FR3010308B1 (fr) * | 2013-09-12 | 2016-11-25 | Oreal | Procede de traitement des fibres keratiniques avec un compose d'acide pyridine dicarboxylique |
| FR3010309B1 (fr) | 2013-09-12 | 2017-03-10 | Oreal | Procede de traitement des fibres keratiniques avec un polysaccharide et un compose de sphingosine |
| FR3030248B1 (fr) | 2014-12-22 | 2018-03-23 | L'oreal | Association derive d'acide pyridine-dicarboxylique/agent anti-oxydant particulier |
| US10788201B2 (en) * | 2018-10-03 | 2020-09-29 | Samuel Harriat | Solar powered boiler assembly |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2809146A (en) * | 1954-09-21 | 1957-10-08 | Phillips Petroleum Co | Method of destroying bacteria employing mercuric-chloride complexes of pyridine |
| US2852519A (en) * | 1954-12-27 | 1958-09-16 | Phillips Petroleum Co | Method for producing esters of heterocyclic nitrogen carboxylic acids |
| FR3795M (fr) * | 1964-09-09 | 1965-12-27 | Metabio Soc | Médicaments a base d'acide quinoléique. |
| FR2123141A6 (en) * | 1971-01-25 | 1972-09-08 | Aries Robert | Organophosphorus pesticidal compsns - stabilized by esters of pyridine dicarboxylic acids |
| DE3002989A1 (de) * | 1980-01-29 | 1981-07-30 | Hoechst Ag, 6000 Frankfurt | Hydroxyphenyl-thiazol, -thiazolin und -thiazolidin-carbonsaeuren, verfahren zu ihrer herstellung und ihre verwendung zur beeinflussung des kollagenstoffwechsels |
-
1984
- 1984-08-31 DE DE19843432094 patent/DE3432094A1/de not_active Withdrawn
-
1985
- 1985-08-21 AT AT85110498T patent/ATE38222T1/de not_active IP Right Cessation
- 1985-08-21 DE DE8585110498T patent/DE3565832D1/de not_active Expired
- 1985-08-21 EP EP85110498A patent/EP0176741B1/de not_active Expired
- 1985-08-29 ES ES546527A patent/ES8609255A1/es not_active Expired
- 1985-08-29 GR GR852098A patent/GR852098B/el unknown
- 1985-08-29 US US06/770,676 patent/US4717727A/en not_active Expired - Lifetime
- 1985-08-30 DK DK397785A patent/DK166127C/da not_active IP Right Cessation
- 1985-08-30 AU AU46928/85A patent/AU588826B2/en not_active Ceased
- 1985-08-30 IE IE215085A patent/IE58599B1/en not_active IP Right Cessation
- 1985-08-30 CA CA000489741A patent/CA1246456A/en not_active Expired
- 1985-08-30 PT PT81058A patent/PT81058B/pt not_active IP Right Cessation
- 1985-08-30 JP JP60189996A patent/JPH0641412B2/ja not_active Expired - Lifetime
- 1985-08-30 ZA ZA856646A patent/ZA856646B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES546527A0 (es) | 1986-07-16 |
| CA1246456A (en) | 1988-12-13 |
| DK166127C (da) | 1993-08-09 |
| DK397785D0 (da) | 1985-08-30 |
| ATE38222T1 (de) | 1988-11-15 |
| PT81058A (de) | 1985-09-01 |
| DE3432094A1 (de) | 1986-03-06 |
| US4717727A (en) | 1988-01-05 |
| EP0176741B1 (de) | 1988-10-26 |
| DK397785A (da) | 1986-03-01 |
| DE3565832D1 (en) | 1988-12-01 |
| IE58599B1 (en) | 1993-10-20 |
| JPS6160655A (ja) | 1986-03-28 |
| ES8609255A1 (es) | 1986-07-16 |
| AU4692885A (en) | 1986-03-06 |
| AU588826B2 (en) | 1989-09-28 |
| IE852150L (en) | 1986-02-28 |
| EP0176741A1 (de) | 1986-04-09 |
| GR852098B (da) | 1986-01-02 |
| PT81058B (pt) | 1987-11-11 |
| ZA856646B (en) | 1986-05-28 |
| JPH0641412B2 (ja) | 1994-06-01 |
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