NO316624B1 - 4-mercaptopyrrolidinderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat - Google Patents
4-mercaptopyrrolidinderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat Download PDFInfo
- Publication number
- NO316624B1 NO316624B1 NO19980467A NO980467A NO316624B1 NO 316624 B1 NO316624 B1 NO 316624B1 NO 19980467 A NO19980467 A NO 19980467A NO 980467 A NO980467 A NO 980467A NO 316624 B1 NO316624 B1 NO 316624B1
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- Norway
- Prior art keywords
- compound
- amino
- ylmethyl
- mmol
- cdcl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 67
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 13
- TZVFQFLWFZUIQS-UHFFFAOYSA-N pyrrolidine-3-thiol Chemical class SC1CCNC1 TZVFQFLWFZUIQS-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 224
- -1 [2S,4S]-4-sulfanylpyrrolidin-2-ylmethyl Chemical group 0.000 claims description 148
- 238000000034 method Methods 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 150000004702 methyl esters Chemical class 0.000 claims description 15
- 125000006239 protecting group Chemical group 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 230000006126 farnesylation Effects 0.000 claims description 7
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 5
- 238000010511 deprotection reaction Methods 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- VDSUAILXEZKWIZ-UHFFFAOYSA-N 4-methylsulfanylbutanoic acid Chemical compound CSCCCC(O)=O VDSUAILXEZKWIZ-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 283
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 218
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
- 238000005481 NMR spectroscopy Methods 0.000 description 155
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 142
- 235000019439 ethyl acetate Nutrition 0.000 description 103
- 239000000243 solution Substances 0.000 description 92
- 239000007858 starting material Substances 0.000 description 90
- 239000000203 mixture Substances 0.000 description 84
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 79
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 70
- 229910001868 water Inorganic materials 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
- 239000007787 solid Substances 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 46
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
- 239000000460 chlorine Substances 0.000 description 31
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 27
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 238000010992 reflux Methods 0.000 description 24
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 23
- 229910052786 argon Inorganic materials 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 150000001299 aldehydes Chemical class 0.000 description 15
- 239000002808 molecular sieve Substances 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 102000016914 ras Proteins Human genes 0.000 description 15
- 108010014186 ras Proteins Proteins 0.000 description 15
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000012267 brine Substances 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 13
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 10
- 239000012300 argon atmosphere Substances 0.000 description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 10
- MEVUPUNLVKELNV-JEDNCBNOSA-N methyl (2s)-2-amino-4-methylsulfanylbutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CCSC MEVUPUNLVKELNV-JEDNCBNOSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 9
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- CSSQGFKSFOSHAM-QWRGUYRKSA-N prop-2-enyl (2s,4s)-2-formyl-4-[(2-methylpropan-2-yl)oxycarbonylsulfanyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)S[C@H]1C[C@@H](C=O)N(C(=O)OCC=C)C1 CSSQGFKSFOSHAM-QWRGUYRKSA-N 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
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- 239000012044 organic layer Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
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- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 6
- ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 6
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- 125000003118 aryl group Chemical group 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 5
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- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
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- YAXUOVOGGJIDTE-UIOOFZCWSA-N tert-butyl [(3s,5s)-5-[[3,3-diphenylpropyl(3-methylbutanoyl)amino]methyl]pyrrolidin-3-yl]sulfanylformate Chemical compound C([C@H]1NC[C@H](C1)SC(=O)OC(C)(C)C)N(C(=O)CC(C)C)CCC(C=1C=CC=CC=1)C1=CC=CC=C1 YAXUOVOGGJIDTE-UIOOFZCWSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GBGB9515975.2A GB9515975D0 (en) | 1995-08-04 | 1995-08-04 | Chemical compounds |
PCT/GB1996/001810 WO1997006138A1 (en) | 1995-08-04 | 1996-07-30 | 4-mercaptopyrrolidine derivatives as farnesyl transferase inhibitors |
Publications (3)
Publication Number | Publication Date |
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NO980467D0 NO980467D0 (no) | 1998-02-03 |
NO980467L NO980467L (no) | 1998-04-03 |
NO316624B1 true NO316624B1 (no) | 2004-03-15 |
Family
ID=10778742
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19980467A NO316624B1 (no) | 1995-08-04 | 1998-02-03 | 4-mercaptopyrrolidinderivater, anvendelse og fremstilling derav, samt farmasoytisk preparat |
NO20024950A NO20024950D0 (no) | 1995-08-04 | 2002-10-15 | 4-Merkaptopyrrolidinderivater som farnesyltransferaseinhibitorer |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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NO20024950A NO20024950D0 (no) | 1995-08-04 | 2002-10-15 | 4-Merkaptopyrrolidinderivater som farnesyltransferaseinhibitorer |
Country Status (23)
Country | Link |
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US (2) | US6232338B1 (pt) |
EP (1) | EP0842151A1 (pt) |
JP (1) | JPH11510178A (pt) |
KR (1) | KR100502770B1 (pt) |
CN (2) | CN1101380C (pt) |
AU (1) | AU720353B2 (pt) |
BR (1) | BR9609701A (pt) |
CA (1) | CA2226671C (pt) |
CZ (1) | CZ293694B6 (pt) |
GB (1) | GB9515975D0 (pt) |
HU (1) | HUP9802857A3 (pt) |
IL (1) | IL123155A0 (pt) |
MX (1) | MX9800946A (pt) |
MY (1) | MY141457A (pt) |
NO (2) | NO316624B1 (pt) |
NZ (1) | NZ313696A (pt) |
PL (1) | PL190873B1 (pt) |
RU (1) | RU2191773C2 (pt) |
SK (1) | SK14598A3 (pt) |
TR (2) | TR200101884T2 (pt) |
TW (1) | TW345575B (pt) |
WO (1) | WO1997006138A1 (pt) |
ZA (1) | ZA966610B (pt) |
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US6204293B1 (en) | 1995-11-06 | 2001-03-20 | University Of Pittsburgh | Inhibitors of protein isoprenyl transferases |
US6221865B1 (en) | 1995-11-06 | 2001-04-24 | University Of Pittsburgh | Inhibitors of protein isoprenyl transferases |
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ES2387211T3 (es) * | 1997-05-07 | 2012-09-18 | University Of Pittsburgh | Inhibidores de proteínas isoprenil transferass |
JP2001520222A (ja) | 1997-10-22 | 2001-10-30 | ゼネカ・リミテッド | イミダゾール誘導体およびファルネシルタンパク質トランスフェラーゼインヒビターとしてのそれらの使用 |
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JP2002503650A (ja) * | 1998-02-10 | 2002-02-05 | アストラゼネカ ユーケー リミテッド | ファルネシルトランスフェラーゼ阻害剤 |
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US8034831B2 (en) * | 2002-11-06 | 2011-10-11 | Celgene Corporation | Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies |
KR20120035234A (ko) | 2003-04-11 | 2012-04-13 | 메디뮨 엘엘씨 | 재조합 il?9 항체 및 그의 용도 |
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-
1995
- 1995-08-04 GB GBGB9515975.2A patent/GB9515975D0/en active Pending
-
1996
- 1996-07-23 TW TW085108987A patent/TW345575B/zh active
- 1996-07-30 MX MX9800946A patent/MX9800946A/es not_active IP Right Cessation
- 1996-07-30 AU AU66223/96A patent/AU720353B2/en not_active Ceased
- 1996-07-30 WO PCT/GB1996/001810 patent/WO1997006138A1/en not_active Application Discontinuation
- 1996-07-30 HU HU9802857A patent/HUP9802857A3/hu unknown
- 1996-07-30 IL IL12315596A patent/IL123155A0/xx not_active IP Right Cessation
- 1996-07-30 NZ NZ313696A patent/NZ313696A/xx unknown
- 1996-07-30 CZ CZ1998309A patent/CZ293694B6/cs not_active IP Right Cessation
- 1996-07-30 CA CA002226671A patent/CA2226671C/en not_active Expired - Fee Related
- 1996-07-30 US US09/011,135 patent/US6232338B1/en not_active Expired - Fee Related
- 1996-07-30 PL PL324819A patent/PL190873B1/pl not_active IP Right Cessation
- 1996-07-30 TR TR2001/01884T patent/TR200101884T2/xx unknown
- 1996-07-30 TR TR1998/00147T patent/TR199800147T1/xx unknown
- 1996-07-30 KR KR1019980700778A patent/KR100502770B1/ko not_active IP Right Cessation
- 1996-07-30 SK SK145-98A patent/SK14598A3/sk unknown
- 1996-07-30 CN CN96197206A patent/CN1101380C/zh not_active Expired - Fee Related
- 1996-07-30 JP JP9508201A patent/JPH11510178A/ja not_active Ceased
- 1996-07-30 BR BR9609701A patent/BR9609701A/pt not_active Application Discontinuation
- 1996-07-30 EP EP96925855A patent/EP0842151A1/en not_active Withdrawn
- 1996-07-30 RU RU98103393/04A patent/RU2191773C2/ru not_active IP Right Cessation
- 1996-08-02 ZA ZA9606610A patent/ZA966610B/xx unknown
- 1996-08-02 MY MYPI96003186A patent/MY141457A/en unknown
-
1998
- 1998-02-03 NO NO19980467A patent/NO316624B1/no unknown
-
2000
- 2000-11-30 US US09/725,964 patent/US6541491B1/en not_active Expired - Fee Related
-
2002
- 2002-03-26 CN CN02108502A patent/CN1377647A/zh active Pending
- 2002-10-15 NO NO20024950A patent/NO20024950D0/no not_active Application Discontinuation
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