NO171020B - Nye tyroninderivater og anvendelse derav - Google Patents
Nye tyroninderivater og anvendelse derav Download PDFInfo
- Publication number
- NO171020B NO171020B NO870077A NO870077A NO171020B NO 171020 B NO171020 B NO 171020B NO 870077 A NO870077 A NO 870077A NO 870077 A NO870077 A NO 870077A NO 171020 B NO171020 B NO 171020B
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- new
- derivatives
- hydrogen
- tyronine
- Prior art date
Links
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
- 239000011630 iodine Substances 0.000 claims abstract description 4
- 238000003127 radioimmunoassay Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- KKCIOUWDFWQUBT-AWEZNQCLSA-N L-thyronine Chemical class C1=CC(C[C@H](N)C(O)=O)=CC=C1OC1=CC=C(O)C=C1 KKCIOUWDFWQUBT-AWEZNQCLSA-N 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- GMRRITAAMQYNSL-UHFFFAOYSA-N 2-methylphosphanylacetic acid Chemical compound CPCC(O)=O GMRRITAAMQYNSL-UHFFFAOYSA-N 0.000 description 2
- BASYEHNVTDGTEF-UHFFFAOYSA-N 2-methylphosphanylpropanoic acid Chemical compound CPC(C)C(O)=O BASYEHNVTDGTEF-UHFFFAOYSA-N 0.000 description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229950008325 levothyroxine Drugs 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- YPIYWJSJNHMIPP-ZOWNYOTGSA-N methyl (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate hydrochloride Chemical compound Cl.IC1=CC(C[C@H](N)C(=O)OC)=CC(I)=C1OC1=CC=C(O)C(I)=C1 YPIYWJSJNHMIPP-ZOWNYOTGSA-N 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- LLUBVCCZUMPBMI-UHFFFAOYSA-N 1-[[ethyl(methyl)phosphoryl]oxy-methylphosphoryl]ethane Chemical compound CCP(C)(=O)OP(C)(=O)CC LLUBVCCZUMPBMI-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- QQWJRNQBMFXZKW-HNNXBMFYSA-N CPCCC(=O)N[C@@H](CC1=CC(I)=C(C(I)=C1)OC1=CC(I)=C(C=C1)O)C(=O)O Chemical compound CPCCC(=O)N[C@@H](CC1=CC(I)=C(C(I)=C1)OC1=CC(I)=C(C=C1)O)C(=O)O QQWJRNQBMFXZKW-HNNXBMFYSA-N 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 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
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- JVMPZZWQWDYQNJ-RSAXXLAASA-N methyl (2s)-2-(diiodoamino)-3-[4-(4-hydroxyphenoxy)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@@H](C(=O)OC)N(I)I)=CC=C1OC1=CC=C(O)C=C1 JVMPZZWQWDYQNJ-RSAXXLAASA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- YRWJRJCUZYGLPN-UHFFFAOYSA-N n-[dimethylamino(methyl)phosphoryl]-n-methylmethanamine Chemical compound CN(C)P(C)(=O)N(C)C YRWJRJCUZYGLPN-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Control Of Electric Motors In General (AREA)
- Fixed Capacitors And Capacitor Manufacturing Machines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Luminescent Compositions (AREA)
- Photoreceptors In Electrophotography (AREA)
- Steroid Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
Foreliggende oppfinnelse vedrører nye tyroninderivater med den generelle formel I
hvori
n "betyr et helt tall mellom 1 og 6,
R betyr hydroksy, (C^-Cf, )-alkyl eller (C^-C^q )-aryl,
R<1> og R<2> er like eller forskjellige og betyr jod eller
hydrogen, og
R<3> betyr hydrogen, ( C^- C^)-alkyl eller (C7-<C>10)-aralkyl, samt
deres salter.
Foretrukket er forbindelse med formel I, hvori R<1> og R<2> har ovennevnte betydning, og n betyr 1 til 4, R betyr hydroksy eller (C1-C4 )-alkyl, og R<3> betyr hydrogen eller (C1-C4)-alkyl, spesielt hydrogen, metyl eller etyl.
Alkyl kan være rettlinjet eller forgrenet. Med { C^- C^ q)-aralkyl forstås f.eks. benzyl eller fenetyl, fortrinnsvis benzyl. ( C^- C^ q)-aryl betyr fortrinnsvis fenyl.
Med salter av forbindelsene med formel I forstås spesielt alkalimetall—, jordalkalimetall— og ammoniumsalter.
Fra esterne for formel I kan forbindelsen med fri karboksyl-gruppe frigjøres på i og for seg kjent måte ved hydrolyse eller hydrogenolyse. Foretrukket er forsåpningen av lavere-alkylesteren med blandet vandige alkalier.
Forbindelsene ifølge oppfinnelsen utmerker seg ved spesi-fikke, for radioimmunoanalysen av tyroninderivater, gunstige oppløselighets—, adsorpsjoris— og bindingsegenskaper.
Forbindelser med formel I kan på vanlig måte (f.eks. ved jodutveksling eller jodering) markeres radioaktivt. Fore-125
trukket er markeringen med isotopen I.
Foreliggende oppfinnelse vedrører også anvendelse av forbindelsen ifølge oppfinnelsen ved gjennomføring av en radipimmunoanalyse.
Oppfinnelsen skal forklares nærmere ved hjelp av noen eksempler.
1) Metylfosfinoacetvl- tetra. 1 odtvronin
I en blanding av 2,5 ml dimetylf ormamid og 2,5 ml metanfosfonsyre-bis-dimetylamid oppløser man 160 mg (1,16 mmol) metylfosfinoeddiksyre og 0,4 ml (3,16 mmol) N-etylmorfolin. Deretter tildryppes under isavkjøling 0,4 ml (2,32 mmol) metyletylfosfinsyreanhydrid. Det omrøres i 10 minutter ved værelsestemperatur og tilsettes deretter 800 mg (1,03 mmol) tyroksin (tetrajodtyronin). Reaksjons-oppløsningen hensettes natten over ved værelsestemperatur, deretter utfelles reaksjonsproduktet ved tilsetning av vann og surgjøring med fortynnet vandig HC1 til pH = 3.
Utbyttet av råprodukt: 920 mg.
Tynnsjiktkromatografi (DC) av produktet (kiselgel 60, (Merck) oppløsningsmiddel CECl3/CH3/0H/iseddik, 100:20:2) viser at utgangsmaterialet tetrajodtyronin er fullstendig omsatt. Rensingen av råproduktet foregår over en kiselgel 60-søyle (4,5 x 35 cm) med oppløsningsmiddelsystemet n-butanol/3,3 % NH4OH/CH3OH (100:20:2). Det som svakt farget, amorft pulver dannede rensede produkt viser en Rf-verdi på 0,75 i det ovennevnte kloroformsystem.
<1>H-NMR-spektrum viser de ventede katakteristika.
2 ) Metyl f osf inoproplonvl- tri. iodtvroninmetvlester
Til en oppløsning av 110 mg metylfosfinopropionsyre (0,72 mmol) og 0,3 ml (2,35 mmol) N-etylmorfolin i 2 ml dimetylester settes under omrøring, isavkjøling og fuktighetsutelukkelse i rekkefølge 360 mg (0,52 mmol) trijodtyroninmetylester-hydroklorid og 220 mg (1,07 mmol) dicykloheksylkarbodiimid, oppløst i 0,5 ml dimetylform-amid. Man lar det oppvarme under omrøring til værelsestemperatur og frasuger deretter etter 28 timers henstand under lys-utelukkelse ved værelsestemperatur fra utfelt dicykloheksylurinstoff. Det etter avdestillering av oppløsningsmidlet gjenblevne rest gjenutfelles flere ganger fra etanol/eter.
Utbytte av råprodukt: 365 mg.
3) Metylfosfinopropionyl- trijodtyronin 348 mg av råproduktet fra eksempel 2 oppløses i 3 ml metanol og oppløsningen omrøres etter tilsetning av 2n vandig natronlut i 4 timer ved pH 12,5 under konstant holding av pH-verdien med luten. Deretter avdamper man fra den med fortynnet vandig saltsyre nøytralisert reaksjons-blanding metanolen i vakuum, opptar i vann og surgjør suspensjonen under omrøring med 2n vandig HC1 til pH 2,5. Utfellingen frasuges, vaskes med vann og tørkes i vakuum over fosforpentoksyd.
Utbytte: 205 mg.
Produktet ble ved elementæranalyse og ^-H-NMR karakterisert som sådant, kiselgel-tynnsjiktkromatografi i flere systemer viste fravær av utgangsmaterialene.
4) Fosfonoacetyl- dl. lodtyronin
Fremstillingen foregikk som omtalt i eksempel 2. Produktet ble etter forsåpning renset ved søylekromatografi på kiselgel i systemet CHCl3/CH30H/H20/iseddik 100:45:6:1,5 og identifisert ^-H-NMR-spektroskopisk.
5) Metylfosfinoacetvi- di. i odtyronin
Forbindelsen ble fremstilt analogt den i eksemplene 2 og 3 omtalte fremgangsmåte. I stedet for metylfosfinopropionsyre ble det anvendt metylfosfinoeddiksyre og i stedet for trijodtyroninmetylester-hydroklorid ble det anvendt dijodtyroninmetylester-hydroklorid. sluttproduktet ble renset ved Inversed Phase - søylekromatografi på kiselgel EP 18 med 75 %- ig metanol som elueringsmiddel. De enhetlige og i DC fra utgangsmaterialene forskjellige stoff av hovedfraksjonen ble identifisert ved masse-spektroskopi som tittelforbindelsen.
Claims (2)
1.
Forbindelse, karakterisert ved den generelle formel I
hvori
n betyr et helt tall mellom 1 og 6,
R betyr hydroksy, (C^-Cf, )-alkyl eller ( C^-C^q )-aryl,
R<1> og R<2> er like eller forskjellige og betyr jod eller
hydrogen og
R<3> betyr hydrogen, (C^-C^)-alkyl eller (C7-C10 )-aralkyl, samt
deres salter.
2.
Anvendelse av en forbindelse ifølge krav 1 ved gjennomføring av en radioimmunoanalyse.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863600365 DE3600365A1 (de) | 1986-01-09 | 1986-01-09 | Neue thyroninderivate |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO870077D0 NO870077D0 (no) | 1987-01-08 |
| NO870077L NO870077L (no) | 1987-07-10 |
| NO171020B true NO171020B (no) | 1992-10-05 |
| NO171020C NO171020C (no) | 1993-01-13 |
Family
ID=6291536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO870077A NO171020C (no) | 1986-01-09 | 1987-01-08 | Nye tyroninderivater og anvendelse derav |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4814484A (no) |
| EP (1) | EP0230056B1 (no) |
| JP (1) | JPH07100708B2 (no) |
| AT (1) | ATE40693T1 (no) |
| CA (1) | CA1269990A (no) |
| DE (2) | DE3600365A1 (no) |
| DK (1) | DK164170C (no) |
| ES (1) | ES2006700B3 (no) |
| FI (1) | FI83656C (no) |
| GR (1) | GR3000057T3 (no) |
| IE (1) | IE59780B1 (no) |
| NO (1) | NO171020C (no) |
| PT (1) | PT84077B (no) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3626468A1 (de) * | 1986-08-05 | 1988-02-11 | Hoechst Ag | Verfahren und testkit zur bestimmung freier wirkstoffe in biologischen fluessigkeiten |
| IT1270260B (it) * | 1994-06-21 | 1997-04-29 | Zambon Spa | Derivati dell'acido fosfonico ad attivita' inibitrice delle metallopeptidasi |
| US7163918B2 (en) * | 2000-08-22 | 2007-01-16 | New River Pharmaceuticals Inc. | Iodothyronine compositions |
| CN109212194B (zh) * | 2018-10-11 | 2020-06-16 | 郑州安图生物工程股份有限公司 | 反三碘甲状腺原氨酸定量检测试剂盒 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4111656A (en) * | 1975-06-26 | 1978-09-05 | Mallinckrodt, Inc. | Radioimmunoassay methods for the determination of l-triiodothyronine and thyroxine |
| US4480041A (en) * | 1982-07-09 | 1984-10-30 | Collaborative Research, Inc. | Use of phosphotriester intermediates for preparation of functionalized liposomes |
-
1986
- 1986-01-09 DE DE19863600365 patent/DE3600365A1/de not_active Withdrawn
- 1986-12-31 ES ES86118188T patent/ES2006700B3/es not_active Expired - Lifetime
- 1986-12-31 EP EP86118188A patent/EP0230056B1/de not_active Expired
- 1986-12-31 AT AT86118188T patent/ATE40693T1/de not_active IP Right Cessation
- 1986-12-31 DE DE8686118188T patent/DE3662048D1/de not_active Expired
-
1987
- 1987-01-07 FI FI870057A patent/FI83656C/fi not_active IP Right Cessation
- 1987-01-07 US US07/001,207 patent/US4814484A/en not_active Expired - Fee Related
- 1987-01-08 IE IE4487A patent/IE59780B1/en not_active IP Right Cessation
- 1987-01-08 DK DK008187A patent/DK164170C/da not_active IP Right Cessation
- 1987-01-08 CA CA000526945A patent/CA1269990A/en not_active Expired - Fee Related
- 1987-01-08 NO NO870077A patent/NO171020C/no not_active IP Right Cessation
- 1987-01-08 JP JP62001162A patent/JPH07100708B2/ja not_active Expired - Lifetime
- 1987-01-08 PT PT84077A patent/PT84077B/pt not_active IP Right Cessation
-
1989
- 1989-05-08 GR GR89400012T patent/GR3000057T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO870077L (no) | 1987-07-10 |
| FI870057A (fi) | 1987-07-10 |
| ES2006700B3 (es) | 1992-04-01 |
| IE59780B1 (en) | 1994-04-06 |
| DK164170C (da) | 1992-10-26 |
| IE870044L (en) | 1987-07-09 |
| FI870057A0 (fi) | 1987-01-07 |
| DK164170B (da) | 1992-05-18 |
| FI83656C (fi) | 1991-08-12 |
| EP0230056A1 (de) | 1987-07-29 |
| DE3662048D1 (de) | 1989-03-16 |
| GR3000057T3 (en) | 1990-10-31 |
| EP0230056B1 (de) | 1989-02-08 |
| US4814484A (en) | 1989-03-21 |
| JPH07100708B2 (ja) | 1995-11-01 |
| PT84077B (pt) | 1989-07-31 |
| ATE40693T1 (de) | 1989-02-15 |
| NO870077D0 (no) | 1987-01-08 |
| JPS62167789A (ja) | 1987-07-24 |
| NO171020C (no) | 1993-01-13 |
| DK8187D0 (da) | 1987-01-08 |
| DK8187A (da) | 1987-07-10 |
| DE3600365A1 (de) | 1987-07-16 |
| FI83656B (fi) | 1991-04-30 |
| PT84077A (de) | 1987-02-01 |
| CA1269990A (en) | 1990-06-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |