FI70572C - Foerfarande foer framstaellning av farmaceutiskt anvaendbara pyrrolidinderivat samt vid deras framstaellning anvaendbara foereningar - Google Patents
Foerfarande foer framstaellning av farmaceutiskt anvaendbara pyrrolidinderivat samt vid deras framstaellning anvaendbara foereningar Download PDFInfo
- Publication number
- FI70572C FI70572C FI802417A FI802417A FI70572C FI 70572 C FI70572 C FI 70572C FI 802417 A FI802417 A FI 802417A FI 802417 A FI802417 A FI 802417A FI 70572 C FI70572 C FI 70572C
- Authority
- FI
- Finland
- Prior art keywords
- methoxybenzoyl
- pyrrolidinone
- hydroxy
- group
- formula
- Prior art date
Links
- 101100148710 Clarkia breweri SAMT gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 41
- 125000006239 protecting group Chemical group 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
- ZUSPUYXHFZBBBB-UHFFFAOYSA-N 3-hydroxy-1-(4-methoxybenzoyl)pyrrolidin-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)C(O)CC1 ZUSPUYXHFZBBBB-UHFFFAOYSA-N 0.000 claims description 13
- 150000003235 pyrrolidines Chemical class 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 8
- XPLNSJFVMBLFNT-UHFFFAOYSA-N 1-(3-hydroxy-4-methoxybenzoyl)pyrrolidin-2-one Chemical compound C1=C(O)C(OC)=CC=C1C(=O)N1C(=O)CCC1 XPLNSJFVMBLFNT-UHFFFAOYSA-N 0.000 claims description 7
- SRMMAOXDXMDUGY-UHFFFAOYSA-N 4-hydroxy-1-(4-methoxybenzoyl)pyrrolidin-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)CC(O)C1 SRMMAOXDXMDUGY-UHFFFAOYSA-N 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 7
- ZUSPUYXHFZBBBB-SNVBAGLBSA-N (3r)-3-hydroxy-1-(4-methoxybenzoyl)pyrrolidin-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)[C@H](O)CC1 ZUSPUYXHFZBBBB-SNVBAGLBSA-N 0.000 claims description 6
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 239000000543 intermediate Substances 0.000 claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 28
- 230000008018 melting Effects 0.000 description 25
- 238000002844 melting Methods 0.000 description 25
- -1 1-substituted 2-pyrrolidinones Chemical class 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 230000010933 acylation Effects 0.000 description 11
- 238000005917 acylation reaction Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 239000005051 trimethylchlorosilane Substances 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000007363 ring formation reaction Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- REUPAAYVMCIRCF-UHFFFAOYSA-N 1-(4-methoxy-3-phenylmethoxybenzoyl)pyrrolidin-2-one Chemical compound COC1=CC=C(C(=O)N2C(CCC2)=O)C=C1OCC1=CC=CC=C1 REUPAAYVMCIRCF-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
- 239000008367 deionised water Substances 0.000 description 6
- 229910021641 deionized water Inorganic materials 0.000 description 6
- 150000002084 enol ethers Chemical class 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 125000004665 trialkylsilyl group Chemical group 0.000 description 6
- RQWAZTJBNFOFEL-SNVBAGLBSA-N (2r)-2-hydroxy-4-[(4-methoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NCC[C@@H](O)C(O)=O)C=C1 RQWAZTJBNFOFEL-SNVBAGLBSA-N 0.000 description 5
- RQWAZTJBNFOFEL-UHFFFAOYSA-N 2-hydroxy-4-[(4-methoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NCCC(O)C(O)=O)C=C1 RQWAZTJBNFOFEL-UHFFFAOYSA-N 0.000 description 5
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 4
- IVUOMFWNDGNLBJ-UHFFFAOYSA-N 4-azaniumyl-2-hydroxybutanoate Chemical compound NCCC(O)C(O)=O IVUOMFWNDGNLBJ-UHFFFAOYSA-N 0.000 description 4
- IXCKJOOGPMRIDP-UHFFFAOYSA-N 4-methoxy-3-phenylmethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1OCC1=CC=CC=C1 IXCKJOOGPMRIDP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000001828 Gelatine Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 4
- DIGCZJDFCSOQLT-LLVKDONJSA-N COC1=CC=C(C=C1)C(=O)N2CC[C@H](C2=O)OC(=O)CCl Chemical compound COC1=CC=C(C=C1)C(=O)N2CC[C@H](C2=O)OC(=O)CCl DIGCZJDFCSOQLT-LLVKDONJSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical compound [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- IVUOMFWNDGNLBJ-GSVOUGTGSA-N (2r)-4-azaniumyl-2-hydroxybutanoate Chemical compound NCC[C@@H](O)C(O)=O IVUOMFWNDGNLBJ-GSVOUGTGSA-N 0.000 description 2
- LUBVCBITQHEVCJ-UHFFFAOYSA-N 1-trimethylsilylpyrrolidin-2-one Chemical compound C[Si](C)(C)N1CCCC1=O LUBVCBITQHEVCJ-UHFFFAOYSA-N 0.000 description 2
- RJVKCDHJOYEBNT-UHFFFAOYSA-N 3-hydroxy-4-[(4-methoxy-3-phenylmethoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NCC(O)CC(O)=O)C=C1OCC1=CC=CC=C1 RJVKCDHJOYEBNT-UHFFFAOYSA-N 0.000 description 2
- MHXGJXWWRBSNPZ-UHFFFAOYSA-N 3-hydroxy-4-[(4-methoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NCC(O)CC(O)=O)C=C1 MHXGJXWWRBSNPZ-UHFFFAOYSA-N 0.000 description 2
- DCYWPUWKWLGIGD-UHFFFAOYSA-N 4-[(4-methoxy-3-phenylmethoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NCCCC(O)=O)C=C1OCC1=CC=CC=C1 DCYWPUWKWLGIGD-UHFFFAOYSA-N 0.000 description 2
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical class COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- KBLFRYWOPDMXTD-SNVBAGLBSA-N [(3r)-1-(4-methoxybenzoyl)-2-oxopyrrolidin-3-yl] 2,2,2-trifluoroacetate Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)[C@H](OC(=O)C(F)(F)F)CC1 KBLFRYWOPDMXTD-SNVBAGLBSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940089960 chloroacetate Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229940078552 o-xylene Drugs 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- PEHFQQWAINXOQG-UHFFFAOYSA-N (2-methoxyacetyl) 2-methoxyacetate Chemical compound COCC(=O)OC(=O)COC PEHFQQWAINXOQG-UHFFFAOYSA-N 0.000 description 1
- MWOFTAPCZWMQPV-PKEIRNPWSA-N (3R)-3-hydroxy-1-(1-methoxycyclohexa-2,4-diene-1-carbonyl)pyrrolidin-2-one Chemical compound COC1(C(=O)N2C([C@@H](CC2)O)=O)CC=CC=C1 MWOFTAPCZWMQPV-PKEIRNPWSA-N 0.000 description 1
- MASDFXZJIDNRTR-UHFFFAOYSA-N 1,3-bis(trimethylsilyl)urea Chemical compound C[Si](C)(C)NC(=O)N[Si](C)(C)C MASDFXZJIDNRTR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DTFMFTPWXDQAPB-UHFFFAOYSA-N 1-(3,4,5-trimethoxybenzoyl)pyrrolidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2C(CCC2)=O)=C1 DTFMFTPWXDQAPB-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- UNDYRLKWGSNWLK-UHFFFAOYSA-N 2-hydroxy-2-[(4-methoxybenzoyl)amino]butanoic acid Chemical compound COC1=CC=C(C(=O)NC(C(=O)O)(CC)O)C=C1 UNDYRLKWGSNWLK-UHFFFAOYSA-N 0.000 description 1
- 125000001627 3 membered heterocyclic group Chemical group 0.000 description 1
- FRKGSNOMLIYPSH-UHFFFAOYSA-N 3-hydroxypyrrolidin-2-one Chemical compound OC1CCNC1=O FRKGSNOMLIYPSH-UHFFFAOYSA-N 0.000 description 1
- KFCHBMSVKKTTFA-UHFFFAOYSA-N 3-trimethylsilyloxypyrrolidin-2-one Chemical compound C[Si](C)(C)OC1CCNC1=O KFCHBMSVKKTTFA-UHFFFAOYSA-N 0.000 description 1
- IOGISYQVOGVIEU-UHFFFAOYSA-N 4-hydroxypyrrolidin-2-one Chemical compound OC1CNC(=O)C1 IOGISYQVOGVIEU-UHFFFAOYSA-N 0.000 description 1
- 150000000565 5-membered heterocyclic compounds Chemical class 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- UVHLGAPWXCUOOX-UHFFFAOYSA-N COC1CC2=CC=CC3=C2C4=C(CCCC14)C=C3 Chemical group COC1CC2=CC=CC3=C2C4=C(CCCC14)C=C3 UVHLGAPWXCUOOX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- KBLFRYWOPDMXTD-UHFFFAOYSA-N [1-(4-methoxybenzoyl)-2-oxopyrrolidin-3-yl] 2,2,2-trifluoroacetate Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)C(OC(=O)C(F)(F)F)CC1 KBLFRYWOPDMXTD-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000007813 chromatographic assay Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000008011 inorganic excipient Substances 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- ASHGTUMKRVIOLH-UHFFFAOYSA-L potassium;sodium;hydrogen phosphate Chemical compound [Na+].[K+].OP([O-])([O-])=O ASHGTUMKRVIOLH-UHFFFAOYSA-L 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH730879 | 1979-08-09 | ||
| CH730879 | 1979-08-09 | ||
| CH475580 | 1980-06-20 | ||
| CH475580 | 1980-06-20 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI802417A FI802417A (fi) | 1981-02-10 |
| FI70572B FI70572B (fi) | 1986-06-06 |
| FI70572C true FI70572C (fi) | 1986-09-24 |
Family
ID=25696222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI802417A FI70572C (fi) | 1979-08-09 | 1980-08-01 | Foerfarande foer framstaellning av farmaceutiskt anvaendbara pyrrolidinderivat samt vid deras framstaellning anvaendbara foereningar |
Country Status (38)
| Country | Link |
|---|---|
| US (1) | US4461906A (hu) |
| EP (1) | EP0024030B1 (hu) |
| KR (2) | KR850000845B1 (hu) |
| AR (1) | AR230625A1 (hu) |
| AT (1) | ATE2894T1 (hu) |
| AU (1) | AU538686B2 (hu) |
| BG (1) | BG34612A3 (hu) |
| CA (1) | CA1124247A (hu) |
| CS (1) | CS214837B2 (hu) |
| CU (1) | CU35300A (hu) |
| DD (1) | DD152337A5 (hu) |
| DE (2) | DE3029671A1 (hu) |
| DK (1) | DK159679C (hu) |
| ES (2) | ES8106290A1 (hu) |
| FI (1) | FI70572C (hu) |
| FR (1) | FR2463127A1 (hu) |
| GB (1) | GB2055835B (hu) |
| GR (1) | GR69911B (hu) |
| HK (1) | HK18486A (hu) |
| HU (1) | HU180596B (hu) |
| IE (1) | IE50090B1 (hu) |
| IL (1) | IL60733A (hu) |
| IN (1) | IN153082B (hu) |
| IT (1) | IT1131959B (hu) |
| LU (1) | LU82692A1 (hu) |
| MC (1) | MC1344A1 (hu) |
| MY (1) | MY8500273A (hu) |
| NL (1) | NL8004025A (hu) |
| NO (1) | NO154632C (hu) |
| NZ (1) | NZ194558A (hu) |
| OA (1) | OA06624A (hu) |
| PH (1) | PH16220A (hu) |
| PL (1) | PL127472B1 (hu) |
| PT (1) | PT71686B (hu) |
| RO (1) | RO82358B (hu) |
| SE (1) | SE8005607L (hu) |
| YU (1) | YU42516B (hu) |
| ZW (1) | ZW16680A1 (hu) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH646149A5 (de) * | 1981-02-05 | 1984-11-15 | Hoffmann La Roche | Pyrrolidin-derivat. |
| FR2515179A1 (fr) * | 1981-07-24 | 1983-04-29 | Hoffmann La Roche | Derives de pyrrolidine, leur procede de preparation, les intermediaires pour leur synthese et leur application therapeutique |
| US4560700A (en) * | 1985-02-08 | 1985-12-24 | Merrell Dow Pharmaceuticals Inc. | Pyrrole-3-carboxylate cardiotonic agents |
| IT1215587B (it) * | 1987-06-26 | 1990-02-14 | Roussel Maestretti Spa | Derivati della 1-benzoil2-oxo 5-alcossi pirrolidina, loro procedimento di preparazione e loro impiego come sostanza medicinale. |
| US5049577A (en) * | 1990-01-29 | 1991-09-17 | E. R. Squibb & Sons, Inc. | 2-pyrrolidone substituted dihydroxy alkanoic, alkenoic and alkynoic acids, compositions and HMG-CoA reductase inhibition therewith |
| US5049578A (en) * | 1990-03-09 | 1991-09-17 | E. R. Squibb & Sons, Inc. | 1-aroyl or 1-acyl-2-2pyrrolidinyl-3,5-dihydroxy alkanoic and alkenoic acids, salts, esters and lactones |
| AU714477B2 (en) * | 1996-04-19 | 2000-01-06 | Regents Of The University Of California, The | Treatment of mood/affective disorders by glutamatergic upmodulators |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2413935A1 (de) * | 1974-03-20 | 1975-10-16 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone |
| DE2541855A1 (de) * | 1975-09-18 | 1977-03-31 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone ii |
| IT1045043B (it) * | 1975-08-13 | 1980-04-21 | Isf Spa | Derivati pirrolidinici |
| CU21107A3 (es) * | 1978-02-10 | 1988-02-01 | Hoffmann La Roche | Pyrrolidines derivatives |
| CA1115212A (en) * | 1978-02-10 | 1981-12-29 | Emilio Kyburz | Pyrrolidine derivatives |
-
1980
- 1980-07-11 NL NL8004025A patent/NL8004025A/nl not_active Application Discontinuation
- 1980-07-11 IT IT23391/80A patent/IT1131959B/it active
- 1980-07-11 CA CA356,013A patent/CA1124247A/en not_active Expired
- 1980-07-16 ZW ZW166/80A patent/ZW16680A1/xx unknown
- 1980-07-28 US US06/172,607 patent/US4461906A/en not_active Expired - Lifetime
- 1980-07-29 BG BG048645A patent/BG34612A3/xx unknown
- 1980-08-01 FI FI802417A patent/FI70572C/fi not_active IP Right Cessation
- 1980-08-01 AR AR282025A patent/AR230625A1/es active
- 1980-08-01 IL IL60733A patent/IL60733A/xx unknown
- 1980-08-01 AU AU60996/80A patent/AU538686B2/en not_active Ceased
- 1980-08-04 NZ NZ194558A patent/NZ194558A/en unknown
- 1980-08-04 CU CU8035300A patent/CU35300A/es unknown
- 1980-08-05 AT AT80104604T patent/ATE2894T1/de active
- 1980-08-05 DE DE19803029671 patent/DE3029671A1/de not_active Withdrawn
- 1980-08-05 HU HU80801943A patent/HU180596B/hu not_active IP Right Cessation
- 1980-08-05 DE DE8080104604T patent/DE3062531D1/de not_active Expired
- 1980-08-05 DD DD80223102A patent/DD152337A5/de unknown
- 1980-08-05 EP EP80104604A patent/EP0024030B1/de not_active Expired
- 1980-08-05 PH PH24407A patent/PH16220A/en unknown
- 1980-08-06 LU LU82692A patent/LU82692A1/de unknown
- 1980-08-06 DK DK338480A patent/DK159679C/da active
- 1980-08-07 GR GR62625A patent/GR69911B/el unknown
- 1980-08-07 FR FR8017448A patent/FR2463127A1/fr active Granted
- 1980-08-07 MC MC801462A patent/MC1344A1/xx unknown
- 1980-08-07 SE SE8005607A patent/SE8005607L/xx not_active Application Discontinuation
- 1980-08-08 KR KR1019800003148A patent/KR850000845B1/ko active
- 1980-08-08 NO NO802370A patent/NO154632C/no unknown
- 1980-08-08 RO RO101940A patent/RO82358B/ro unknown
- 1980-08-08 CS CS805497A patent/CS214837B2/cs unknown
- 1980-08-08 ES ES494091A patent/ES8106290A1/es not_active Expired
- 1980-08-08 PT PT71686A patent/PT71686B/pt unknown
- 1980-08-08 IE IE1676/80A patent/IE50090B1/en not_active IP Right Cessation
- 1980-08-08 GB GB8025938A patent/GB2055835B/en not_active Expired
- 1980-08-08 IN IN908/CAL/80A patent/IN153082B/en unknown
- 1980-08-08 YU YU2006/80A patent/YU42516B/xx unknown
- 1980-08-09 PL PL1980226164A patent/PL127472B1/pl unknown
- 1980-08-09 OA OA57192A patent/OA06624A/xx unknown
-
1981
- 1981-03-16 ES ES500381A patent/ES8301209A1/es not_active Expired
-
1984
- 1984-07-21 KR KR1019840004335A patent/KR850000843B1/ko not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY273/85A patent/MY8500273A/xx unknown
-
1986
- 1986-03-20 HK HK184/86A patent/HK18486A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2141478C1 (ru) | Амиды, фармацевтическая композиция, способы снижения секреции аполипопротеина в, соединение | |
| KR20090033912A (ko) | 화학적 화합물 | |
| HU223752B1 (hu) | A gasztrointesztinális keringést elősegítő gyógyászati készítmény | |
| US5158970A (en) | Proline derivatives | |
| CA1088930A (en) | Preparation of 9-hydroxy tetrahydropyranyl substituted prostaglandin intermediates | |
| FI70572C (fi) | Foerfarande foer framstaellning av farmaceutiskt anvaendbara pyrrolidinderivat samt vid deras framstaellning anvaendbara foereningar | |
| JPS6222986B2 (hu) | ||
| EP0206090A2 (en) | Peptide renin inhibitors | |
| EP0229566B1 (fr) | Dérivés de la 1-benzène sulfonyl 2-oxo 5-alcoxy pyrrolidine, leur procédé de préparation, leur application comme médicaments et les compositions les renfermant | |
| FR2577925A1 (fr) | Aminoalcanoylureido amino et imino acides et esters a substituant ester, a proprietes therapeutiques | |
| US5446050A (en) | Azabicyclo amides and esters as 5-HT3 receptor antagonists | |
| JPS61100564A (ja) | ペプチドで置換された複素環免疫促進剤 | |
| FR2758329A1 (fr) | Derives d'imidazole-4-butane boronique, leur preparation et leur utilisation en therapeutique | |
| KR100297180B1 (ko) | 인지질유도체및이의제조방법 | |
| CA1113934A (en) | Process for the manufacture of piperazinopyrrolobenzodiazepines | |
| EP0233800A1 (fr) | Dérivés d'imidazo[1,2-a]quinoléines, leur préparation et leur application en thérapeutique | |
| RU2181722C2 (ru) | Способ получения и промежуточные соединения для получения ингибиторов 5-липоксигеназы | |
| CH620678A5 (en) | Process for the preparation of a derivative of piperidine | |
| SU1028246A3 (ru) | Способ получени производных пирролидина | |
| EP0145304B1 (en) | Tetrahydro-beta-carboline derivatives and process for the preparation thereof | |
| BE899255R (fr) | Betta-oxo-alpha-carbanoyl-pyrrolpropionitriles, procede pour leur preparation, preparations pharmaceutiques contenant ces composes, ainsi que leur application therapeutique. | |
| WO1998022443A1 (fr) | Derives de n-(imidazolylbutyle) benzenesulfonamide ayant une activite antithrombotique | |
| HU215112B (hu) | Eljárás gyulladáscsökkentő 1-heteroaril-3-acil-2-oxindol-származékok előállítására | |
| EP0971916A1 (fr) | Derives de n-(arginyl)benzenesulfonamide et leur utilisation comme agents antithrombotiques | |
| FR2699921A1 (fr) | Dérivés d'acide 2-(thien-2-yl)imidazo[2,1-b]benzothiazole-3-acétique, leur préparation et leur application en thérapeutique. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE AG |