DK152125B - Analogifremgangsmaade til fremstilling af 1-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion - Google Patents
Analogifremgangsmaade til fremstilling af 1-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion Download PDFInfo
- Publication number
- DK152125B DK152125B DK487476AA DK487476A DK152125B DK 152125 B DK152125 B DK 152125B DK 487476A A DK487476A A DK 487476AA DK 487476 A DK487476 A DK 487476A DK 152125 B DK152125 B DK 152125B
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- DK
- Denmark
- Prior art keywords
- nitrophenyl
- dimethylimidazolidine
- trifluoromethyl
- trifluormethyl
- dion
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 4
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 6
- JQULXIOYDDCNGR-UHFFFAOYSA-N 2-amino-2-methylpropanenitrile Chemical compound CC(C)(N)C#N JQULXIOYDDCNGR-UHFFFAOYSA-N 0.000 claims description 3
- YCZPVAWKLUWQBP-UHFFFAOYSA-N 4-isocyanato-1-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1C(F)(F)F YCZPVAWKLUWQBP-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims 1
- 125000006501 nitrophenyl group Chemical group 0.000 claims 1
- 230000009102 absorption Effects 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 9
- 210000002307 prostate Anatomy 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 5
- 230000002280 anti-androgenic effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229960001712 testosterone propionate Drugs 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 210000001625 seminal vesicle Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 201000010653 vesiculitis Diseases 0.000 description 3
- HIIVFEJATHLJHA-UHFFFAOYSA-N 5-imino-4,4-dimethyl-1-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidin-2-one Chemical compound N=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 HIIVFEJATHLJHA-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000786363 Rhampholeon spectrum Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000556 factor analysis Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 1- (3'-trifluoromethyl-4'-nitrophenyl) -4,4-dimethylphenylimidazolidin-2,5-dione Chemical compound 0.000 description 1
- ZZKDGABMFBCSRP-UHFFFAOYSA-N 3-ethyl-2-methylpyridine Chemical compound CCC1=CC=CN=C1C ZZKDGABMFBCSRP-UHFFFAOYSA-N 0.000 description 1
- KXALCBULAZGRHX-UHFFFAOYSA-N 4-amino-1,5-dihydroimidazol-2-one Chemical compound NC1=NC(=O)NC1 KXALCBULAZGRHX-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Electromechanical Clocks (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
DK 152125 B
- i -
Opfindelsen angår en analogifremgangsmåde til fremstilling af den hidtil ukendte forbindelse l-(31-trifluor-methyl-4'-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion med den i kravets indledning angivne formel I.
5 Denne forbindelse har interessante farmakologiske egenskaber. Man har navnlig konstateret, at den inhibe-rer virkningerne af androgener på de perifere receptorer uden at øve nogen indflydelse på hypofysens normale funktion .
10 De forsøg, som er anført i den eksperimentelle del nedenfor, illustrerer denne antiandrogene virkning på rotter.
Som følge af sin antiandrogene virkning og sin uskadelighed over for hypofysens funktion kan forbindelsen med 15 formlen I anvendes i terapien, dels hos børn og unge uden risiko for vækststandsning, dels hos voksne uden risiko for visse effekter i retning af kemisk kastrering.
1—(31-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimi-dazolidin-2,5-dion finder navnlig anvendelse som medikament 20 til behandling af adenomer og neoplasi i prostata, hirsu-tisme, acne, seborrhagi og for kraftig hårvækst.
Forbindelsen kan ligeledes finde anvendelse på det veterinære område.
Den kan anvendes ad parenteral, oral, perlingual el-25 ler rektal vej eller i topisk applikation.
Fremgangsmåden til fremstilling af den hidtil ukendte forbindelse med den almene formel I er ejendommelig ved det i kravets kendetegnende del anførte.
Den tertiære base, i hvis nærværelse man udfører kon-30 densationen af 2-amino-2-cyanpropan med 3-trifluormethyl- 4-nitrophenylisocyanat, kan navnlig være pyridin, methyl-ethylpyridin eller triethylamin.
Denne kondensation udføres med fordel i et organisk opløsningsmiddel såsom tetrahydrofuran, ether eller iso-3 5 propylether.
- 2 -
DK 152125B
Den syre, i hvis nærværelse man udfører hydrolysen af 1—(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethyl-5-iminoimidazolidin-2-on, kan navnlig være saltsyre eller svovlsyre.
5 Nedenstående eksempel illustrerer fremgangsmåden ifølge opfindelsen.
Eksempel
Fremstilling af l-(31-trifluormethyl-4'-nitrophenyl)- 4.4- dimethylimidazolidin-2,5-dion 10 Trin A: 1-(3'-trifluormethyl-4 *-nitrophenyl)-4,4-dimethyl- 5-iminoimidazolidin-2-on I 500 ml tetrahydrofuran indfører man 49,6 g 3-tri-fluormethyl-4-nitrophenylisocyanat, 1 ml triethylamin samt hurtigt 18 g 2-amino-2-cyanpropan, og man omrører i 72 ti-15 mer ved 20°C, inddamper til tørhed ved destillation under formindsket tryk, chromatograferer resten på silicagel under eluering med en blanding af methylenchlorid og acetone i forholdet 8:2 og får 27 g l-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethyl-5-iminoimidazolidin-2-on med 20 smp. 168°C.
Analyse: ^12H11F3N4^3 beregnet: C% 45,57 H% 3,50 N% 17,71 fundet: 45,6 3,6 17,5 I.R. spektrum (chloroform): 25 -1
Absorption ved 3442 cm , som er karakteristisk for NH, absorption ved 1755 cm som er karakteristisk for C=0, absorption ved 1673 cm som er karakteristisk for C=N, absorptioner ved 1615 og 1595 cm *", som er karakteristiske for den aromatiske ring, og absorptioner ved 1542, 30 -1 1492 og 1355 cm , som er karakteristiske for NC^-Trin B: 1—(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethyl- imidazolidin-2,5-dion I en blanding af 35 ml 22°Bé vandig saltsyre og 35 ml vand indfører man 10 g l-(3'-trifluormethyl-4'-nitrophenyl)-35 4.4- dimethyl-5-iminoimidazolidin-2-on, opvarmer suspensionen til tilbagesvaling i 1 time, afkøler til 20°C, hælder i vand, isolerer den dannede udfældning ved frasugning,
DK 152125B
- 3 - vasker den, tørrer den og får 9,5 g l-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion med smp. 14 9 ° C.
En prøve med mikroanalytisk renhed fås ved krystalli-5 sation af ethanol. Smp. 149°C.
Analyse: ^12^10^3^3^4 beregnet: C% 45,43 H% 3,17 F% 17,96 N% 13,24 fundet: 45,5 3,4 17,9 12,9 I.R. spektrum (chloroform):
Absorption ved 3438 cm som er karakteristisk for NH, absorptioner ved 1792 og 1734 cm \ som er karakteristiske for C=0, absorptioner ved 1613, 1597 og 1501 cm *", som er karakteristiske for den aromatiske ring, og absorptioner ved 1545, 1358 og 1349 cm *", som er karakteristiske for NC^·
Farmakologisk undersøgelse af l-(31-trifluormethyl-41-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion (forbindelse A)
Forsøgene udføres på rotter af stammen Sprague-Dawley, 20 som er kastreret ad skrotal vej under anæstesi med ether.
Produkterne indgives i opløsning i sesamolie indeholdende 5% benzylalkohol i et rumfang på 0,1 ml.
A) Antiandrogen virkning på rotter
Grupper på 5 kastrerede hanrotter på 75 + 5g modtager 25 dagligt i 7 dage samtidige indgifter ad subkutan ve] af testosteronpropionat (50 pg pr. rotte pr. dag) og af det produkt, som skal undersøges (1 mg pr. rotte pr. dag).
Dyrene aflives 24 timer efter den sidste indgift.
Prostata og sædblærerne fjernes og fikseres i 24 timer i 3Q
en isotonisk saltopløsning tilsat 10% formaldehydopløsning, hvorpå de dissekeres og vejes. Inhiberingen af vægtforøgelsen af genitalorganerne hidført af androgenet muliggør vurderingen af den antiandrogene aktivitet af det undersøgte produkt.
Kontrolgrupperne undergår ikke nogen behandling, og andre grupper modtager kun testosteronpropionat eller det produkt, som skal undersøges.
35 - 4 -
DK 152125B
Variationerne i vægtene af prostata eller af sædblærerne homogeniseres ved logaritmisk transformation ifølge Bartlett (J. Roy. Stat. Soc., 1937, Suppl. 4, 137), og homogeniteten verificeres ved Bartlett's kontrol 5 (Biometrics, 1947, _3' 39). Resultaterne analyseres ved faktoranalyse.
De i tabellerne anførte værdier repræsenterer gennemsnittene ledsaget af den typiske fejl.
Der fås følgende resultater: Sædblærer Ventral prostata Grupper_ vægt i mg vægt i mg
Kontrol 11,5+0,9 16,8+1,0
Testosteronpropionat 79,6+8,1 90,3+7,0
Forbindelse A 12,3+0,8 15,0+1,3 15 Testosteronpropionat + forbindelse A 17,2 +2,9* 45,0 + 4,3* * Faktoranalyse p .£0,01.
1—(31-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimi-dazolidin-2,5-dion fremkalder en inhibering af vægtforøgel-2Q sen af sædblærerne på 92% og af prostata på 61%. Dette produkt udviser altså en god antiandrogen virkning over for testosteronpropionat.
B) Radioaktivitetsprøve, vedrørende inhibering af prostatainkorporering efter injektion af en 25 spordosis af -H-testosteron på rotte
Grupper på 3 kastrerede hanrotter på 70 +10 g, der er kastreret 24 timer i forvejen, modtager i subkutan injektion 5 mg af det produkt, som skal undersøges. 16 timer senere modtager dyrene i intramuskulær injektion 10 pCi/ 2Q 100 g e(- H-testosteron (26 Ci/mmol i alkoholisk opløsning. Dyrene aflives 1 time efter injektionen af det tritiumhol-dige hormon. Den ventrale prostata fjernes, skylles i en isotonisk natriumchloridopløsning, vejes og solubiliseres derefter ved alkalisk behandling.
25 Radioaktiviteten af prøverne måles efter tilsætning af 15 ml scintillerende væske.
- 5 -
DK 152125B
De opnåede resultater udtrykkes i % inhibering af inkorporeringen af testosteron:
Inkorporering
Grupper_ d. p. m/mq* % inhibering 5 Kontrol 114+4
Forbindelse A 35+8 68% * d. p. m/mg = desintegration pr. minut pr. mg frisk prostatavæv.
1-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimetfeyl-10 imidazolidin-2,5-dion formindsker altså inkorporeringen af det tritiumholdige hormon i prostata.
15
Claims (1)
- DK 152125B - 6 - Analogifremgangsmåde til fremstilling af l-(3'-tri-fluormethyl-4'-nitrophenyl)-4,4-dimethylimidazolidin- 2,5-dion med formlen I 0 Γτρ>» °2N']^ I Xc“3 10 *3C kendetegnet ved, at man i nærværelse af en tertiær base omsætter 2-amino-2-cyanpropan med 3-trifluor-methyl-4-nitrophenylisocyanat til opnåelse af l-(3'-tri-15 fluormethyl-41-nitrophenyl)-4,4-dimethyl-5-iminoimidazo-lidin-2-on, som man hydrolyserer i surt miljø til opnåelse af forbindelsen med formlen I. 20
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7533084A FR2329276A1 (fr) | 1975-10-29 | 1975-10-29 | Nouvelles imidazolidines substituees, procede de preparation, application comme medicament et compositions les renfermant |
| FR7533084 | 1975-10-29 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK487476A DK487476A (da) | 1977-04-30 |
| DK152125B true DK152125B (da) | 1988-02-01 |
| DK152125C DK152125C (da) | 1988-06-20 |
Family
ID=9161795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK487476A DK152125C (da) | 1975-10-29 | 1976-10-28 | Analogifremgangsmaade til fremstilling af 1-(3'-trifluormethyl-4'-nitrophenyl)-4,4-dimethylimidazolidin-2,5-dion |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4097578A (da) |
| JP (1) | JPS6011701B2 (da) |
| AU (1) | AU500542B2 (da) |
| BE (1) | BE847742A (da) |
| BG (1) | BG60533B2 (da) |
| CA (1) | CA1086751A (da) |
| CH (1) | CH599164A5 (da) |
| DE (1) | DE2649925C2 (da) |
| DK (1) | DK152125C (da) |
| ES (1) | ES452746A1 (da) |
| FR (1) | FR2329276A1 (da) |
| GB (1) | GB1518444A (da) |
| GE (1) | GEP19970948B (da) |
| IE (1) | IE43875B1 (da) |
| LU (2) | LU76085A1 (da) |
| NL (2) | NL187102C (da) |
| SE (1) | SE430502B (da) |
| SU (1) | SU596165A3 (da) |
Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL55774A (en) * | 1977-10-28 | 1982-04-30 | Sparamedica Ag | Pharmaceutical compositions containing urea derivatives,certain such novel derivatives and their manufacture |
| MC1220A1 (fr) * | 1977-10-28 | 1979-07-20 | Hoffmann La Roche | Nouveaux derives d'imidazolidine |
| FI801184A7 (fi) * | 1979-04-24 | 1981-01-01 | F Hoffmann La Roche & Co | Menetelmä imidatsolidiini-johdannaisten valmistamiseksi. |
| WO1986001105A1 (en) * | 1984-08-02 | 1986-02-27 | Fernand Labrie | Pharmaceutical composition for combination therapy of hormone dependent cancers |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB997037A (en) * | 1962-03-19 | 1965-06-30 | Ici Ltd | New hydrantoin derivatives |
| JPS4920973B1 (da) * | 1970-05-28 | 1974-05-29 | ||
| JPS5136332B1 (da) * | 1970-12-09 | 1976-10-07 | ||
| IL45459A (en) * | 1973-09-03 | 1978-01-31 | Ciba Geigy Ag | 1-(dichlorofluoromethylthio)-3-phenyl-imidazolidine-2,4-dione derivatives their preparation and their use as bactericides and fungicides |
-
1975
- 1975-10-29 FR FR7533084A patent/FR2329276A1/fr active Granted
-
1976
- 1976-09-30 SE SE7610859A patent/SE430502B/xx not_active IP Right Cessation
- 1976-10-20 NL NLAANVRAGE7611576,A patent/NL187102C/xx not_active IP Right Cessation
- 1976-10-21 SU SU762414002A patent/SU596165A3/ru active
- 1976-10-21 US US05/734,557 patent/US4097578A/en not_active Expired - Lifetime
- 1976-10-27 ES ES452746A patent/ES452746A1/es not_active Expired
- 1976-10-28 BE BE171876A patent/BE847742A/xx not_active IP Right Cessation
- 1976-10-28 CA CA264,606A patent/CA1086751A/fr not_active Expired
- 1976-10-28 DK DK487476A patent/DK152125C/da not_active IP Right Cessation
- 1976-10-28 AU AU19095/76A patent/AU500542B2/en not_active Expired
- 1976-10-28 LU LU76085A patent/LU76085A1/xx unknown
- 1976-10-29 JP JP51129586A patent/JPS6011701B2/ja not_active Expired
- 1976-10-29 CH CH1369176A patent/CH599164A5/de active Protection Beyond IP Right Term
- 1976-10-29 GB GB45034/76A patent/GB1518444A/en not_active Expired
- 1976-10-29 DE DE2649925A patent/DE2649925C2/de not_active Expired
- 1976-10-29 IE IE2419/76A patent/IE43875B1/en not_active IP Right Cessation
-
1993
- 1993-06-03 LU LU88282C patent/LU88282I2/fr unknown
- 1993-06-17 NL NL930079C patent/NL930079I2/nl unknown
- 1993-09-09 GE GEAP19931536A patent/GEP19970948B/en unknown
-
1994
- 1994-02-22 BG BG098507A patent/BG60533B2/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE430502B (sv) | 1983-11-21 |
| CH599164A5 (da) | 1978-05-12 |
| DE2649925C2 (de) | 1986-08-28 |
| IE43875L (en) | 1977-04-29 |
| FR2329276A1 (fr) | 1977-05-27 |
| SU596165A3 (ru) | 1978-02-28 |
| AU500542B2 (en) | 1979-05-24 |
| NL187102C (nl) | 1991-06-03 |
| ES452746A1 (es) | 1977-10-01 |
| GEP19970948B (en) | 1997-04-18 |
| US4097578A (en) | 1978-06-27 |
| CA1086751A (fr) | 1980-09-30 |
| LU76085A1 (da) | 1977-05-31 |
| BG60533B2 (bg) | 1995-07-28 |
| DK487476A (da) | 1977-04-30 |
| GB1518444A (en) | 1978-07-19 |
| DE2649925A1 (de) | 1977-05-12 |
| NL930079I1 (nl) | 1993-09-16 |
| SE7610859L (sv) | 1977-04-30 |
| BE847742A (fr) | 1977-04-28 |
| NL930079I2 (nl) | 1993-10-01 |
| AU1909576A (en) | 1978-05-04 |
| NL187102B (nl) | 1991-01-02 |
| IE43875B1 (en) | 1981-06-17 |
| FR2329276B1 (da) | 1979-09-14 |
| DK152125C (da) | 1988-06-20 |
| NL7611576A (nl) | 1977-05-03 |
| JPS6011701B2 (ja) | 1985-03-27 |
| JPS5257176A (en) | 1977-05-11 |
| LU88282I2 (fr) | 1994-05-04 |
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| PUP | Patent expired |