NO324051B1 - 2-okso-1-pyrrolidinderivater, fremgangsmate for fremstilling av disse og anvendelse av dem - Google Patents
2-okso-1-pyrrolidinderivater, fremgangsmate for fremstilling av disse og anvendelse av dem Download PDFInfo
- Publication number
- NO324051B1 NO324051B1 NO20023995A NO20023995A NO324051B1 NO 324051 B1 NO324051 B1 NO 324051B1 NO 20023995 A NO20023995 A NO 20023995A NO 20023995 A NO20023995 A NO 20023995A NO 324051 B1 NO324051 B1 NO 324051B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- alkyl
- aryl
- general formula
- halogen
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 36
- 238000002360 preparation method Methods 0.000 title claims description 20
- -1 hydroxy, amino Chemical group 0.000 claims description 96
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 239000003054 catalyst Substances 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000004104 aryloxy group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000005110 aryl thio group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 229940124530 sulfonamide Drugs 0.000 claims description 12
- 150000003456 sulfonamides Chemical class 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 10
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 8
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 4
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 3
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical compound CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- JSLASWSJHUAUMT-UHFFFAOYSA-N 2H-tetrazol-5-yl benzenesulfonate Chemical compound C=1C=CC=CC=1S(=O)(=O)OC1=NN=NN1 JSLASWSJHUAUMT-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 238000005915 ammonolysis reaction Methods 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims 3
- ZDGXMOZHFUQHKZ-UHFFFAOYSA-N 2-(3-ethyl-2-oxopyrrolidin-1-yl)acetamide Chemical compound CCC1CCN(CC(N)=O)C1=O ZDGXMOZHFUQHKZ-UHFFFAOYSA-N 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000007858 starting material Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 18
- 125000005843 halogen group Chemical group 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- 229910052786 argon Inorganic materials 0.000 description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
- 239000010948 rhodium Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 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 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 125000002946 cyanobenzyl group Chemical group 0.000 description 13
- 125000006277 halobenzyl group Chemical group 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 125000004802 cyanophenyl group Chemical group 0.000 description 12
- 125000005059 halophenyl group Chemical group 0.000 description 12
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 12
- 125000006502 nitrobenzyl group Chemical group 0.000 description 12
- 125000006501 nitrophenyl group Chemical group 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 10
- 229960004002 levetiracetam Drugs 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 125000003396 thiol group Chemical class [H]S* 0.000 description 9
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 5
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
- 238000004296 chiral HPLC Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 229910052703 rhodium Inorganic materials 0.000 description 5
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 5
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000002738 chelating agent Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229910052707 ruthenium Inorganic materials 0.000 description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- VYXHVRARDIDEHS-QGTKBVGQSA-N (1z,5z)-cycloocta-1,5-diene Chemical compound C\1C\C=C/CC\C=C/1 VYXHVRARDIDEHS-QGTKBVGQSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011141 high resolution liquid chromatography Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- XPIWVCAMONZQCP-UHFFFAOYSA-N methyl 2-oxobutanoate Chemical compound CCC(=O)C(=O)OC XPIWVCAMONZQCP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical compound COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 2
- ZYVYEJXMYBUCMN-UHFFFAOYSA-N 1-methoxy-2-methylpropane Chemical compound COCC(C)C ZYVYEJXMYBUCMN-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
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- 229910019213 POCl3 Inorganic materials 0.000 description 2
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- 229920006362 Teflon® Polymers 0.000 description 2
- 238000006136 alcoholysis reaction Methods 0.000 description 2
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- 229940126062 Compound A Drugs 0.000 description 1
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
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- HPHUVLMMVZITSG-UHFFFAOYSA-N Etiracetam Chemical compound CCC(C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-UHFFFAOYSA-N 0.000 description 1
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Classifications
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Applications Claiming Priority (2)
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GBGB0004297.8A GB0004297D0 (en) | 2000-02-23 | 2000-02-23 | 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses |
PCT/EP2001/001956 WO2001064637A1 (en) | 2000-02-23 | 2001-02-21 | 2-oxo-1-pyrrolidine derivatives, process for preparing them and their uses |
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NO20023995A NO324051B1 (no) | 2000-02-23 | 2002-08-22 | 2-okso-1-pyrrolidinderivater, fremgangsmate for fremstilling av disse og anvendelse av dem |
NO20023997A NO324485B1 (no) | 2000-02-23 | 2002-08-22 | 2-okso-1-pyrrolidinderivater, farmasøytisk preparat og deres anvendelse for fremstilling av et medikament |
NO20053644A NO20053644L (no) | 2000-02-23 | 2005-07-27 | (2S)-2-[(4S)-4-(2,2-difluorvinyl)-2-oksopyrrolidinyl ]butanamid og farmasoytisk preparat |
NO20053645A NO20053645L (no) | 2000-02-23 | 2005-07-27 | (4R)- og (4S)-diastereoisomerer av (2S)-2-[ 2-oksy-4-propylpyrrolidinyl]butanamid og farmasoytisk preparat inneholdende disse |
NO2016005C NO2016005I1 (no) | 2000-02-23 | 2016-03-08 | 2-okso-1-pyrrolidinderivater, farmasøytisk preparat og deres anvendelse for fremstilling av et medikament |
NO2023025C NO2023025I1 (no) | 2000-02-23 | 2023-06-20 | Brivaracetam - forlengelse |
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NO20023997A NO324485B1 (no) | 2000-02-23 | 2002-08-22 | 2-okso-1-pyrrolidinderivater, farmasøytisk preparat og deres anvendelse for fremstilling av et medikament |
NO20053644A NO20053644L (no) | 2000-02-23 | 2005-07-27 | (2S)-2-[(4S)-4-(2,2-difluorvinyl)-2-oksopyrrolidinyl ]butanamid og farmasoytisk preparat |
NO20053645A NO20053645L (no) | 2000-02-23 | 2005-07-27 | (4R)- og (4S)-diastereoisomerer av (2S)-2-[ 2-oksy-4-propylpyrrolidinyl]butanamid og farmasoytisk preparat inneholdende disse |
NO2016005C NO2016005I1 (no) | 2000-02-23 | 2016-03-08 | 2-okso-1-pyrrolidinderivater, farmasøytisk preparat og deres anvendelse for fremstilling av et medikament |
NO2023025C NO2023025I1 (no) | 2000-02-23 | 2023-06-20 | Brivaracetam - forlengelse |
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