FI112475B - Uusia, mahdollisesti substituoituja fenyyli-imidatsolidiineja, menetelmä niiden valmistamiseksi, niiden käyttö lääkkeinä ja niitä käsittävät farmaseuttiset koostumukset - Google Patents
Uusia, mahdollisesti substituoituja fenyyli-imidatsolidiineja, menetelmä niiden valmistamiseksi, niiden käyttö lääkkeinä ja niitä käsittävät farmaseuttiset koostumukset Download PDFInfo
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- FI112475B FI112475B FI962754A FI962754A FI112475B FI 112475 B FI112475 B FI 112475B FI 962754 A FI962754 A FI 962754A FI 962754 A FI962754 A FI 962754A FI 112475 B FI112475 B FI 112475B
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- compound
- trifluoromethyl
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- 238000002360 preparation method Methods 0.000 title claims description 15
- 239000003814 drug Substances 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 229940079593 drug Drugs 0.000 title claims description 3
- TVPNGVPSNXPYLT-UHFFFAOYSA-N 1-phenylimidazolidine Chemical class C1NCCN1C1=CC=CC=C1 TVPNGVPSNXPYLT-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 207
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- -1 halogen radical Chemical class 0.000 claims description 51
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 238000006460 hydrolysis reaction Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
- 230000007062 hydrolysis Effects 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000003254 radicals Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 235000005985 organic acids Nutrition 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Chemical group 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- BNJMRELGMDUDDB-UHFFFAOYSA-N $l^{1}-sulfanylbenzene Chemical group [S]C1=CC=CC=C1 BNJMRELGMDUDDB-UHFFFAOYSA-N 0.000 claims description 2
- WBKHZBSPXBTZDB-UHFFFAOYSA-N 5-(fluoromethyl)-1,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione Chemical compound O=C1C(CF)(C)N(C)C(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 WBKHZBSPXBTZDB-UHFFFAOYSA-N 0.000 claims description 2
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- PNXRQXIVPNUMTI-UHFFFAOYSA-N 4-[3-(2-fluoroethyl)-4-(fluoromethyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound O=C1C(C)(CF)N(CCF)C(=O)N1C1=CC=C(C#N)C(C(F)(F)F)=C1 PNXRQXIVPNUMTI-UHFFFAOYSA-N 0.000 claims 1
- 230000002280 anti-androgenic effect Effects 0.000 abstract description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 88
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- 239000000243 solution Substances 0.000 description 63
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 238000002329 infrared spectrum Methods 0.000 description 40
- 239000002904 solvent Substances 0.000 description 39
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 34
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000013078 crystal Substances 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- 238000004452 microanalysis Methods 0.000 description 20
- 238000002211 ultraviolet spectrum Methods 0.000 description 20
- 238000000746 purification Methods 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 238000004587 chromatography analysis Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000003921 oil Substances 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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- 101100452236 Caenorhabditis elegans inf-1 gene Proteins 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 6
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- NDYWSWDCOWRLOQ-UHFFFAOYSA-N CCN(CC)SN(CC)CC.F.F.F Chemical compound CCN(CC)SN(CC)CC.F.F.F NDYWSWDCOWRLOQ-UHFFFAOYSA-N 0.000 description 5
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- 239000001923 methylcellulose Substances 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229960003632 minoxidil Drugs 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
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 235000015393 sodium molybdate Nutrition 0.000 description 1
- 239000011684 sodium molybdate Substances 0.000 description 1
- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 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
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical group ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- 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
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- 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
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
-
- 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
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9400042A FR2715402B1 (fr) | 1994-01-05 | 1994-01-05 | Nouvelles phénylimidazolines éventuellement substituées, leur procédé et des intermédiaires de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant. |
| FR9400042 | 1994-01-05 | ||
| FR9410660 | 1994-09-06 | ||
| FR9410660A FR2724169B1 (fr) | 1994-09-06 | 1994-09-06 | Nouvelles phenylimidazolidines eventuellement substituees, leur procede et des intermediaires de preparation, leur application comme medicaments et les compositions pharmaceutiques les renfermant |
| FR9500004 | 1995-01-04 | ||
| PCT/FR1995/000004 WO1995018794A1 (fr) | 1994-01-05 | 1995-01-04 | Nouvelles phenylimidazolidines eventuellement substituees, leur procede et des intermediaires de preparation, leur application comme medicaments et les compositions pharmaceutiques les renfermant |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI962754L FI962754L (fi) | 1996-07-04 |
| FI962754A0 FI962754A0 (fi) | 1996-07-04 |
| FI112475B true FI112475B (fi) | 2003-12-15 |
Family
ID=26230882
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI962754A FI112475B (fi) | 1994-01-05 | 1996-07-04 | Uusia, mahdollisesti substituoituja fenyyli-imidatsolidiineja, menetelmä niiden valmistamiseksi, niiden käyttö lääkkeinä ja niitä käsittävät farmaseuttiset koostumukset |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5750553A (da) |
| EP (1) | EP0738263B1 (da) |
| JP (1) | JPH09507241A (da) |
| KR (1) | KR100372065B1 (da) |
| CN (1) | CN1113873C (da) |
| AT (1) | ATE200281T1 (da) |
| AU (1) | AU687152B2 (da) |
| BR (1) | BR9506457A (da) |
| CA (1) | CA2180379A1 (da) |
| DE (1) | DE69520560T2 (da) |
| DK (1) | DK0738263T3 (da) |
| ES (1) | ES2156204T3 (da) |
| FI (1) | FI112475B (da) |
| GR (1) | GR3035853T3 (da) |
| HU (1) | HUT76299A (da) |
| IL (1) | IL111908A (da) |
| MA (1) | MA23423A1 (da) |
| PT (1) | PT738263E (da) |
| TW (1) | TW521073B (da) |
| WO (1) | WO1995018794A1 (da) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2741342B1 (fr) * | 1995-11-22 | 1998-02-06 | Roussel Uclaf | Nouvelles phenylimidazolidines fluorees ou hydroxylees, procede, intermediaires de preparation, application comme medicaments, nouvelle utilisation et compositions pharmaceutiques |
| FR2742749B1 (fr) * | 1995-12-22 | 1998-02-06 | Roussel Uclaf | Nouvelles phenylimidazolidines comportant notamment un radical nitrooxy ou carbonyloxy, procede et intermediaires de preparation, application comme medicaments, nouvelles utilisations et compositions pharmaceutiques |
| ES2191286T3 (es) * | 1997-03-03 | 2003-09-01 | Boehringer Ingelheim Pharma | Moleculas pequeñas, utiles en el tratamiento de enfermedades inflamatorias. |
| USRE38132E1 (en) | 1997-03-03 | 2003-06-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Phenylpyrrolidines, phenylimidazolidines,3-phenyl-1,3-oxizolidines and 3-phenyl-1,3-thiazolidines and their use in the treatment of inflammatory disease |
| US6355664B1 (en) | 1997-03-03 | 2002-03-12 | Boehringer Ingelheim Pharmaceuticals, Inc. | Phenylpyrrolidines, phenylimidazolidines, 3-phenyl-1,3-oxizolidines and 3-phenyl-1,3-thiazolidines and their use in the treatment of inflammatory disease |
| IL142598A0 (en) * | 1998-10-23 | 2002-03-10 | Aventis Pharma Gmbh | Preparations for topical application of substances having antiandrogenic effect |
| US6184249B1 (en) * | 1998-12-18 | 2001-02-06 | Biophysica, Inc. | Androgen receptor suppressors in the therapy and diagnosis of prostate cancer, alopecia and other hyper-androgenic syndromes |
| WO2001007052A1 (en) | 1999-07-21 | 2001-02-01 | Boehringer Ingelheim Pharmaceuticals, Inc. | Small molecules useful in the treatment of inflammatory disease |
| US6492408B1 (en) * | 1999-07-21 | 2002-12-10 | Boehringer Ingelheim Pharmaceuticals, Inc. | Small molecules useful in the treatment of inflammatory disease |
| WO2001007044A1 (en) | 1999-07-21 | 2001-02-01 | Boehringer Ingelheim Pharmaceuticals, Inc. | Small molecules useful in the treatment of inflammatory disease |
| JP3833532B2 (ja) | 1999-07-21 | 2006-10-11 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 炎症性疾患の治療において有用な小分子 |
| US6828458B2 (en) | 2000-05-25 | 2004-12-07 | Biophysica, Inc. | Topical antiandrogen for hair loss and other hyperandrogenic conditions |
| US7001911B2 (en) * | 2000-06-28 | 2006-02-21 | Bristol-Myers Squibb Company | Fused cyclic modulators of nuclear hormone receptor function |
| US20040077605A1 (en) | 2001-06-20 | 2004-04-22 | Salvati Mark E. | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
| MXPA02012605A (es) | 2000-06-28 | 2003-05-14 | Squibb Bristol Myers Co | Moduladores selectivos del receptor androgeno y metodo para su identificacion, dise°o y uso. |
| US6953679B2 (en) | 2000-09-19 | 2005-10-11 | Bristol-Myers Squibb Company | Method for the preparation of fused heterocyclic succinimide compounds and analogs thereof |
| EP1854798A3 (en) * | 2000-09-19 | 2007-11-28 | Bristol-Myers Squibb Company | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
| US20040087548A1 (en) | 2001-02-27 | 2004-05-06 | Salvati Mark E. | Fused cyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
| DE10141443B4 (de) * | 2001-08-23 | 2007-02-01 | Christos C. Prof. Dr. Zouboulis | Verwendung von molekularbiologisch hergestellten, nicht-viralen Wirkstoffen zur Behandlung der Akne |
| HRP20040311A2 (en) * | 2001-10-01 | 2005-02-28 | Bristol-Myers Squibb Company Cerep SA | Spiro-hydantoin compounds useful as anti-inflammatory agents |
| US7087636B2 (en) | 2001-12-19 | 2006-08-08 | Bristol-Myers Squibb Company | Fused heterocyclic compounds and analogs thereof, modulators of nuclear hormone receptor function |
| US6875438B2 (en) * | 2002-04-27 | 2005-04-05 | Aventis Pharma Deutschland Gmbh | Preparations for topical administration of substances having antiandrogenic activity |
| ATE502298T1 (de) * | 2003-12-19 | 2011-04-15 | Univ California | Verfahren und materialien zur beurteilung von prostatakrebstherapien |
| AU2011202578B2 (en) * | 2004-02-24 | 2012-03-22 | The Regents Of The University Of California | Methods and materials for assessing prostate cancer therapies and compounds |
| NZ550102A (en) * | 2004-02-24 | 2010-10-29 | Univ California | Methods and materials for assessing prostate cancer therapies and compounds (thiohydantoine derivatives) |
| US8470829B2 (en) | 2004-09-09 | 2013-06-25 | Chugai Seiyaku Kabushiki Kaisha | Imidazolidine derivative and use thereof |
| CA2579514A1 (en) * | 2004-09-10 | 2006-03-23 | Janssen Pharmaceutica N.V. | Novel imidazolidin-2-one derivatives as selective androgen receptor modulators (sarms) |
| TW200616634A (en) * | 2004-10-01 | 2006-06-01 | Bristol Myers Squibb Co | Crystalline forms and process for preparing spiro-hydantoin compounds |
| US20060142319A1 (en) * | 2004-12-14 | 2006-06-29 | Bang-Chi Chen | Pyridyl-substituted spiro-hydantoin crystalline forms and process |
| US7186727B2 (en) * | 2004-12-14 | 2007-03-06 | Bristol-Myers Squibb Company | Pyridyl-substituted spiro-hydantoin compounds and use thereof |
| US7709517B2 (en) * | 2005-05-13 | 2010-05-04 | The Regents Of The University Of California | Diarylhydantoin compounds |
| US7709516B2 (en) | 2005-06-17 | 2010-05-04 | Endorecherche, Inc. | Helix 12 directed non-steroidal antiandrogens |
| SI2656842T1 (sl) | 2006-03-27 | 2016-10-28 | The Regents Of The University Of California | Modulator androgenih receptorjev za zdravljenje raka prostate in bolezni, povezanih z androgenimi receptorji |
| WO2007127010A2 (en) | 2006-03-29 | 2007-11-08 | The Regents Of The University Of California | Diarylthiohydantoin compounds |
| GB0610765D0 (en) * | 2006-05-31 | 2006-07-12 | Proskelia Sas | Imidazolidine derivatives, uses therefor, preparation thereof and compositions comprising such |
| US8168667B2 (en) * | 2006-05-31 | 2012-05-01 | Galapagos Nv | Imidazolidine derivatives, uses therefor, preparation thereof and compositions comprising such |
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| EP2620432A3 (en) | 2007-10-26 | 2013-12-18 | The Regents Of the University of California | Diarylhydantoin compounds |
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| GB2463514C (en) * | 2008-09-11 | 2018-09-26 | Galapagos Nv | Imidazolidine compounds and uses therefor |
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| WO2010141330A1 (en) | 2009-06-02 | 2010-12-09 | Boehringer Ingelheim International Gmbh | DERIVATIVES OF 6,7-DIHYDRO-5H-IMIDAZO[1,2-a]IMIDAZOLE-3-CARBOXYLIC ACID AMIDES |
| BRPI1012581A2 (pt) | 2009-06-02 | 2016-03-29 | Boehringer Ingelheim Int | derivados de amidas de ácido 6, 7-di-hidro-5h-imidazol[1,2-a]imidazol-3-carboxílico |
| RU2012114770A (ru) | 2009-09-04 | 2013-10-10 | Вандербилт Юниверсити | АЛЛОСТЕРИЧЕСКИЕ СРЕДСТВА ПОТЕНЦИРОВАНИЯ mGluR4, КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ НЕВРОЛОГИЧЕСКИХ ДИСФУНКЦИЙ |
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| UY34646A (es) | 2012-03-02 | 2013-10-31 | Novartis Ag | Compuestos de espirohidantoína y su uso como moduladores selectivos del receptor de andrógenos |
| NZ744456A (en) | 2012-09-26 | 2019-09-27 | Aragon Pharmaceuticals Inc | Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer |
| PL2945628T3 (pl) | 2013-01-15 | 2020-09-21 | Aragon Pharmaceuticals, Inc. | Modulator receptorów androgenowych w skojarzeniu z octanem abirateronu i prednizonem do leczenia nowotworu stercza |
| US9682960B2 (en) | 2013-12-19 | 2017-06-20 | Endorecherche, Inc. | Non-steroidal antiandrogens and selective androgen receptor modulators with a pyridyl moiety |
| TWI726969B (zh) | 2016-01-11 | 2021-05-11 | 比利時商健生藥品公司 | 用作雄性激素受體拮抗劑之經取代之硫尿囊素衍生物 |
| US10702508B2 (en) | 2017-10-16 | 2020-07-07 | Aragon Pharmaceuticals, Inc. | Anti-androgens for the treatment of non-metastatic castration-resistant prostate cancer |
| US11981660B2 (en) | 2018-03-21 | 2024-05-14 | University Of Miami | Neurite outgrowth promoters and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE1032258B (de) * | 1956-12-20 | 1958-06-19 | Kali Chemie Ag | Verfahren zur Herstellung von in 5-Stellung mono- und disubstituierten 1-Aryl-hydantoinen |
| GB997037A (en) * | 1962-03-19 | 1965-06-30 | Ici Ltd | New hydrantoin derivatives |
| DK123717B (da) * | 1968-11-25 | 1972-07-24 | Sumitomo Chemical Co | 3-(3',5'-Dihalogenphenyl)-imidazolidin-2,4-dionderivater med mirobicid virkning. |
| JPS5136332B1 (da) * | 1970-12-09 | 1976-10-07 | ||
| US4093444A (en) * | 1973-05-22 | 1978-06-06 | Pepro, Societe Pour Le Developpement Et La Vente De Specialites Chimiques | Hydantoin derivatives and methods for regulating plant-growth |
| FR2329276A1 (fr) * | 1975-10-29 | 1977-05-27 | Roussel Uclaf | Nouvelles imidazolidines substituees, procede de preparation, application comme medicament et compositions les renfermant |
| DE2540872A1 (de) * | 1975-09-13 | 1977-03-24 | Basf Ag | Hydantoin-derivate |
| JPS52113965A (en) * | 1976-03-22 | 1977-09-24 | Nippon Soda Co Ltd | Hydantoin derivatives, their preparation, fungicides for agriculture a nd gardening use containing the same |
| JPS53112875A (en) * | 1977-03-15 | 1978-10-02 | Sumitomo Chem Co Ltd | 1-chlorocarbonylmethyl-3-(3,5-dichlorophenyl)hydantoin, its preparation and industrial bactericide containing the same |
| JPS53124267A (en) * | 1977-04-06 | 1978-10-30 | Sumitomo Chem Co Ltd | 1-alkoxyacyl-3-(3,5-dihalogenophenyl)hydantoin derivatives, their preparation and bactericides for agricultural and horticultural uses containing the same as active agent |
| JPS5427564A (en) * | 1977-08-02 | 1979-03-01 | Sumitomo Chem Co Ltd | 1-branched alkylcarbonyl-3-(3,5-dihalogenophenyl) hydantoins, their preparation, and bactericides for pomicultural and horticultural uses containing the same as active agent. |
| 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. |
| BE884897R (fr) * | 1980-08-22 | 1981-02-23 | Hoffmann La Roche | Preparations pharmaceutiques |
| US4753957A (en) * | 1981-09-28 | 1988-06-28 | Rohm And Haas Company | Substituted 2,4-imidazolidinediones and fungicidal compositions |
| EP0091596B1 (de) * | 1982-04-08 | 1991-09-11 | Shell Internationale Researchmaatschappij B.V. | Neue Hydantoine, ihre Herstellung und Verwendung |
| FR2619381B1 (fr) * | 1987-08-13 | 1989-12-08 | Roussel Uclaf | Nouvelles imidazolidines substituees par un radical hydroxymethyle et un radical phenyl substitue, leur procede de preparation, leur application comme medicaments, les compositions pharmaceutiques les renfermant et un intermediaire pour leur preparation |
| FR2671348B1 (fr) * | 1991-01-09 | 1993-03-26 | Roussel Uclaf | Nouvelles phenylimidazolidines, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les renfermant. |
| US5411981A (en) * | 1991-01-09 | 1995-05-02 | Roussel Uclaf | Phenylimidazolidines having antiandrogenic activity |
| FR2693461B1 (fr) * | 1992-07-08 | 1994-09-02 | Roussel Uclaf | Nouvelles phénylimidazolidines substituées, leur procédé de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant. |
| FR2694290B1 (fr) * | 1992-07-08 | 1994-09-02 | Roussel Uclaf | Nouvelles phénylimidazolidines éventuellement substituées, leur procédé de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant. |
-
1994
- 1994-12-05 TW TW083111272A patent/TW521073B/zh not_active IP Right Cessation
- 1994-12-07 IL IL11190894A patent/IL111908A/xx not_active IP Right Cessation
-
1995
- 1995-01-03 MA MA23750A patent/MA23423A1/fr unknown
- 1995-01-04 PT PT95906361T patent/PT738263E/pt unknown
- 1995-01-04 KR KR1019960703612A patent/KR100372065B1/ko not_active Expired - Fee Related
- 1995-01-04 US US08/669,419 patent/US5750553A/en not_active Expired - Fee Related
- 1995-01-04 WO PCT/FR1995/000004 patent/WO1995018794A1/fr not_active Ceased
- 1995-01-04 AT AT95906361T patent/ATE200281T1/de not_active IP Right Cessation
- 1995-01-04 ES ES95906361T patent/ES2156204T3/es not_active Expired - Lifetime
- 1995-01-04 EP EP95906361A patent/EP0738263B1/fr not_active Expired - Lifetime
- 1995-01-04 CA CA002180379A patent/CA2180379A1/fr not_active Abandoned
- 1995-01-04 HU HU9601836A patent/HUT76299A/hu unknown
- 1995-01-04 DK DK95906361T patent/DK0738263T3/da active
- 1995-01-04 JP JP7518337A patent/JPH09507241A/ja active Pending
- 1995-01-04 BR BR9506457A patent/BR9506457A/pt not_active IP Right Cessation
- 1995-01-04 AU AU14573/95A patent/AU687152B2/en not_active Ceased
- 1995-01-04 DE DE69520560T patent/DE69520560T2/de not_active Expired - Fee Related
- 1995-01-04 CN CN95191761A patent/CN1113873C/zh not_active Expired - Fee Related
-
1996
- 1996-07-04 FI FI962754A patent/FI112475B/fi not_active IP Right Cessation
-
2001
- 2001-05-11 GR GR20010400704T patent/GR3035853T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU1457395A (en) | 1995-08-01 |
| DE69520560T2 (de) | 2001-09-13 |
| EP0738263B1 (fr) | 2001-04-04 |
| HUT76299A (en) | 1997-07-28 |
| DK0738263T3 (da) | 2001-06-18 |
| EP0738263A1 (fr) | 1996-10-23 |
| HU9601836D0 (en) | 1996-09-30 |
| ES2156204T3 (es) | 2001-06-16 |
| IL111908A0 (en) | 1995-03-15 |
| US5750553A (en) | 1998-05-12 |
| WO1995018794A1 (fr) | 1995-07-13 |
| AU687152B2 (en) | 1998-02-19 |
| IL111908A (en) | 2003-05-29 |
| CN1141631A (zh) | 1997-01-29 |
| CA2180379A1 (fr) | 1995-07-13 |
| DE69520560D1 (de) | 2001-05-10 |
| KR100372065B1 (ko) | 2003-05-12 |
| GR3035853T3 (en) | 2001-08-31 |
| MA23423A1 (fr) | 1995-10-01 |
| TW521073B (en) | 2003-02-21 |
| FI962754L (fi) | 1996-07-04 |
| PT738263E (pt) | 2001-08-30 |
| CN1113873C (zh) | 2003-07-09 |
| ATE200281T1 (de) | 2001-04-15 |
| JPH09507241A (ja) | 1997-07-22 |
| BR9506457A (pt) | 1997-10-07 |
| FI962754A0 (fi) | 1996-07-04 |
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