PH26373A - Azacyclic carboxylic acid derivatives - Google Patents
Azacyclic carboxylic acid derivatives Download PDFInfo
- Publication number
- PH26373A PH26373A PH38628A PH38628A PH26373A PH 26373 A PH26373 A PH 26373A PH 38628 A PH38628 A PH 38628A PH 38628 A PH38628 A PH 38628A PH 26373 A PH26373 A PH 26373A
- Authority
- PH
- Philippines
- Prior art keywords
- ethyl
- methanone
- oxime
- thienyl
- hydrochloride
- Prior art date
Links
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 2
- 150000002923 oximes Chemical class 0.000 claims abstract description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract 2
- -1 4-triazolyl Chemical group 0.000 claims description 94
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 90
- 150000001875 compounds Chemical class 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000028579 gamma-aminobutyric acid uptake involved in synaptic transmission Effects 0.000 abstract description 5
- 230000000946 synaptic effect Effects 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 26
- 238000000034 method Methods 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 238000010992 reflux Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229940093499 ethyl acetate Drugs 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- 229960004756 ethanol Drugs 0.000 description 9
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 9
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 229940093956 potassium carbonate Drugs 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- MHZJWHBLWIWKAW-UHFFFAOYSA-N (2-methylphenyl)-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)C=2C(=CC=CC=2)C)=C1C MHZJWHBLWIWKAW-UHFFFAOYSA-N 0.000 description 5
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- VMHYWKBKHMYRNF-UHFFFAOYSA-N (2-chlorophenyl)-phenylmethanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1 VMHYWKBKHMYRNF-UHFFFAOYSA-N 0.000 description 4
- RPWCLFUNNRFLDQ-UHFFFAOYSA-N 1-[2-(benzhydrylideneamino)oxyethyl]piperidin-1-ium-3-carboxylic acid;chloride Chemical compound Cl.C1C(C(=O)O)CCCN1CCON=C(C=1C=CC=CC=1)C1=CC=CC=C1 RPWCLFUNNRFLDQ-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- QPRFAFKPBOLMDI-UHFFFAOYSA-N bis(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1C QPRFAFKPBOLMDI-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- QTDZOWFRBNTPQR-UHFFFAOYSA-N guvacine Chemical compound OC(=O)C1=CCCNC1 QTDZOWFRBNTPQR-UHFFFAOYSA-N 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- KWPPSQDQWBZCFB-UHFFFAOYSA-N (2,4-dichlorophenyl)-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C KWPPSQDQWBZCFB-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 229960000443 hydrochloric acid Drugs 0.000 description 3
- 235000011167 hydrochloric acid Nutrition 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- DNYZBFWKVMKMRM-UHFFFAOYSA-N n-benzhydrylidenehydroxylamine Chemical compound C=1C=CC=CC=1C(=NO)C1=CC=CC=C1 DNYZBFWKVMKMRM-UHFFFAOYSA-N 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- CKGKXGQVRVAKEA-UHFFFAOYSA-N (2-methylphenyl)-phenylmethanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1 CKGKXGQVRVAKEA-UHFFFAOYSA-N 0.000 description 2
- NCLNHRBANMOMAJ-UHFFFAOYSA-N (3-azidophenyl)-phenylmethanone Chemical compound [N-]=[N+]=NC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 NCLNHRBANMOMAJ-UHFFFAOYSA-N 0.000 description 2
- MNSUUGIRUZUBQV-UHFFFAOYSA-N (3-fluorophenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC(F)=C1 MNSUUGIRUZUBQV-UHFFFAOYSA-N 0.000 description 2
- VZIQDRZAQCBKLB-UHFFFAOYSA-N (4-chloro-2-methylphenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1C VZIQDRZAQCBKLB-UHFFFAOYSA-N 0.000 description 2
- NNHFTYXKYCVPFN-UHFFFAOYSA-N 1-(4,4-diphenylbut-3-enyl)-3,6-dihydro-2h-pyridine-5-carboxylic acid Chemical compound C1C(C(=O)O)=CCCN1CCC=C(C=1C=CC=CC=1)C1=CC=CC=C1 NNHFTYXKYCVPFN-UHFFFAOYSA-N 0.000 description 2
- TXQKSMSLZVKQBI-UHFFFAOYSA-N 1-(4,4-diphenylbut-3-enyl)-3-piperidinecarboxylic acid Chemical compound C1C(C(=O)O)CCCN1CCC=C(C=1C=CC=CC=1)C1=CC=CC=C1 TXQKSMSLZVKQBI-UHFFFAOYSA-N 0.000 description 2
- NGNALWDRPKNJGR-UHFFFAOYSA-N 1-[2-[(diphenylmethylene)amino]oxyethyl]-3,6-dihydro-2H-pyridine-5-carboxylic acid Chemical compound C1C(C(=O)O)=CCCN1CCON=C(C=1C=CC=CC=1)C1=CC=CC=C1 NGNALWDRPKNJGR-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000016285 Movement disease Diseases 0.000 description 2
- 208000021642 Muscular disease Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 101150107341 RERE gene Proteins 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- UBEYHGOSWVDVJA-UHFFFAOYSA-N bis(4-fluoro-2-methylphenyl)methanone Chemical compound CC1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1C UBEYHGOSWVDVJA-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- HYMOUMXFUKZVRZ-UHFFFAOYSA-N ethyl 1-(3-bromopropyl)piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCN(CCCBr)C1 HYMOUMXFUKZVRZ-UHFFFAOYSA-N 0.000 description 2
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- JPCBFNIZUIYWIP-UHFFFAOYSA-N (1-methylimidazol-2-yl)-phenylmethanone Chemical compound CN1C=CN=C1C(=O)C1=CC=CC=C1 JPCBFNIZUIYWIP-UHFFFAOYSA-N 0.000 description 1
- UOBZEBGRMJZFRG-UHFFFAOYSA-N (2-chlorophenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1Cl UOBZEBGRMJZFRG-UHFFFAOYSA-N 0.000 description 1
- AKOIZRNUSISGGJ-UHFFFAOYSA-N (2-fluorophenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1F AKOIZRNUSISGGJ-UHFFFAOYSA-N 0.000 description 1
- MJVJDBDSHRVKPT-UHFFFAOYSA-N (3,4-dichlorophenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=C(Cl)C(Cl)=C1 MJVJDBDSHRVKPT-UHFFFAOYSA-N 0.000 description 1
- SHULEACXTONYPS-UHFFFAOYSA-N (3-hydroxyphenyl)-phenylmethanone Chemical compound OC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 SHULEACXTONYPS-UHFFFAOYSA-N 0.000 description 1
- GPCRPXYMNLWATE-UHFFFAOYSA-N (3-methoxyphenyl)-(2-methylphenyl)methanone Chemical compound COC1=CC=CC(C(=O)C=2C(=CC=CC=2)C)=C1 GPCRPXYMNLWATE-UHFFFAOYSA-N 0.000 description 1
- VMFJVWPCRCAWBS-UHFFFAOYSA-N (3-methoxyphenyl)-phenylmethanone Chemical compound COC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 VMFJVWPCRCAWBS-UHFFFAOYSA-N 0.000 description 1
- MFYLRNKOXORIPK-UHFFFAOYSA-N (3-nitrophenyl)-phenylmethanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 MFYLRNKOXORIPK-UHFFFAOYSA-N 0.000 description 1
- QYHGIOKVIOPZSO-UHFFFAOYSA-N (4-chloro-2-methylphenyl)-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)C=2C(=CC(Cl)=CC=2)C)=C1C QYHGIOKVIOPZSO-UHFFFAOYSA-N 0.000 description 1
- XFCWZEUPNDVHCR-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=C(F)C=C1C XFCWZEUPNDVHCR-UHFFFAOYSA-N 0.000 description 1
- MWBOMRDQCKGNRM-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)C=2C(=CC(F)=CC=2)C)=C1C MWBOMRDQCKGNRM-UHFFFAOYSA-N 0.000 description 1
- OGTSHGYHILFRHD-UHFFFAOYSA-N (4-fluorophenyl)-phenylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=CC=C1 OGTSHGYHILFRHD-UHFFFAOYSA-N 0.000 description 1
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 1
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 1
- ZASZCKQEHQQNHY-UHFFFAOYSA-N 1-(4-phenyl-4-thiophen-2-ylbut-3-enyl)piperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1CCC=C(C=1C=CC=CC=1)C1=CC=CS1 ZASZCKQEHQQNHY-UHFFFAOYSA-N 0.000 description 1
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- DLQPOZVMYHDIBA-UHFFFAOYSA-N n-(2-chloroethoxy)-1,1-diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=NOCCCl)C1=CC=CC=C1 DLQPOZVMYHDIBA-UHFFFAOYSA-N 0.000 description 1
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- NFGGQMYSOLVBLF-UHFFFAOYSA-N phenyl(1h-pyrrol-2-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CN1 NFGGQMYSOLVBLF-UHFFFAOYSA-N 0.000 description 1
- GCSHUYKULREZSJ-UHFFFAOYSA-N phenyl(pyridin-2-yl)methanone Chemical compound C=1C=CC=NC=1C(=O)C1=CC=CC=C1 GCSHUYKULREZSJ-UHFFFAOYSA-N 0.000 description 1
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- ZFACJPAPCXRZMQ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O.OC(=O)C1=CC=CC=C1C(O)=O ZFACJPAPCXRZMQ-UHFFFAOYSA-N 0.000 description 1
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- 230000003518 presynaptic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Luminescent Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK270488A DK270488D0 (da) | 1988-05-18 | 1988-05-18 | Hidtil ukendte o-substituerede ketoximer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PH26373A true PH26373A (en) | 1992-06-01 |
Family
ID=8114842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PH38628A PH26373A (en) | 1988-05-18 | 1989-05-05 | Azacyclic carboxylic acid derivatives |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5039685A (de) |
| EP (1) | EP0342635B1 (de) |
| JP (1) | JP2824661B2 (de) |
| KR (1) | KR900018058A (de) |
| AT (1) | ATE110064T1 (de) |
| AU (1) | AU622178B2 (de) |
| CA (1) | CA1337123C (de) |
| DE (1) | DE68917517T2 (de) |
| DK (1) | DK270488D0 (de) |
| ES (1) | ES2058383T3 (de) |
| FI (1) | FI93955C (de) |
| IE (1) | IE66016B1 (de) |
| IL (1) | IL90313A0 (de) |
| NO (1) | NO177262C (de) |
| NZ (1) | NZ229136A (de) |
| PH (1) | PH26373A (de) |
| PT (1) | PT90607B (de) |
| ZA (1) | ZA893733B (de) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK704488D0 (da) * | 1988-12-19 | 1988-12-19 | Novo Industri As | Nye n-substituerede azaheterocykliske carboxylsyrer |
| JP2765876B2 (ja) * | 1988-10-24 | 1998-06-18 | 科研製薬株式会社 | ピリジルケトオキシムエーテル誘導体 |
| DK93791D0 (da) * | 1991-05-17 | 1991-05-17 | Novo Nordisk As | Nye heterocykliske carboxylsyrer |
| EP0543780A3 (en) * | 1991-11-21 | 1993-09-01 | Ciba-Geigy Ag | Novel aminoalkanephosphinic acids and their salts |
| TW266206B (de) * | 1993-04-28 | 1995-12-21 | Takeda Pharm Industry Co Ltd | |
| DK74393D0 (da) * | 1993-06-23 | 1993-06-23 | Novo Nordisk As | Novel heterocyclic chemistry |
| DK74493D0 (da) * | 1993-06-23 | 1993-06-23 | Novo Nordisk As | Novel heterocyclic chemistry |
| US5962449A (en) | 1995-04-07 | 1999-10-05 | Novo Nordisk A/S | Tricyclic compounds in treating hyperalgesic conditions and NIDDM |
| ATE189814T1 (de) * | 1996-04-15 | 2000-03-15 | Takeda Chemical Industries Ltd | Hydroxypyridin-derivate, ihre herstellung und ihre pharmazeutische verwendung |
| WO1997049403A1 (en) * | 1996-06-27 | 1997-12-31 | University College Dublin | Use of nipecotic acid or guvacine derivatives for the manufacture of a medicament for the treatment of postischemic neurodegenerative disorders |
| EP1142584A4 (de) * | 1999-01-12 | 2003-04-16 | Takeda Chemical Industries Ltd | Zusammensetzungen zur behandlung häufigen harnlassens sowie harninkontinenz |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235931A (en) * | 1967-04-05 | 1980-11-25 | Duphar International Research B.V. | Compounds having pharmacological properties |
| FR2162312B1 (de) * | 1971-12-10 | 1975-02-07 | Buzas Andre | |
| FR2248033B1 (de) * | 1973-10-19 | 1977-03-11 | Cerpha | |
| US4207319A (en) * | 1973-10-19 | 1980-06-10 | Albert Rolland S.A. | Thienyl or furyl phenyl O-hetero amino alkyl oximes and use thereof |
| US4148911A (en) * | 1977-07-08 | 1979-04-10 | Societe Anonyme Dite Albert Rolland S.A. | Method of treating respiratory disorders |
| DE2851387A1 (de) * | 1977-11-28 | 1979-06-07 | Degussa | Aminoaethyloxime mit mindestens einem thienylrest und verfahren zu deren herstellung |
| AU532700B2 (en) * | 1979-04-02 | 1983-10-13 | Sumitomo Chemical Company, Limited | Diphenylalkanoether |
| JPS5626863A (en) * | 1979-08-13 | 1981-03-16 | Sumitomo Chem Co Ltd | Novel diphenylalkanone oxime derivative |
| US4722930A (en) * | 1980-03-01 | 1988-02-02 | John Wyeth And Brother Limited | 3-benzoyl-1-[(oxo or thioheteroaryl-ylalkyl)-piperid-4-yl]ureas and derivatives |
| US4514414A (en) * | 1982-10-25 | 1985-04-30 | Smithkline Beckman Corporation | N-Substituted pyrrolidineacetic acids and their esters |
| FI864246A (fi) * | 1985-11-08 | 1987-05-09 | Warner Lambert Co | N-substituerade 3-piperidin- eller 3-pyridinkarboxylsyror samt deras derivat. |
| ES2059360T3 (es) * | 1986-01-07 | 1994-11-16 | Novo Nordisk As | Nuevos derivados de aminoacidos. |
-
1988
- 1988-05-18 DK DK270488A patent/DK270488D0/da not_active Application Discontinuation
-
1989
- 1989-05-05 PH PH38628A patent/PH26373A/en unknown
- 1989-05-10 US US07/350,151 patent/US5039685A/en not_active Expired - Fee Related
- 1989-05-11 IE IE153389A patent/IE66016B1/en not_active IP Right Cessation
- 1989-05-16 IL IL90313A patent/IL90313A0/xx not_active IP Right Cessation
- 1989-05-16 NZ NZ229136A patent/NZ229136A/en unknown
- 1989-05-16 AU AU34845/89A patent/AU622178B2/en not_active Ceased
- 1989-05-16 NO NO891970A patent/NO177262C/no not_active IP Right Cessation
- 1989-05-17 CA CA000599974A patent/CA1337123C/en not_active Expired - Fee Related
- 1989-05-17 ES ES89108850T patent/ES2058383T3/es not_active Expired - Lifetime
- 1989-05-17 EP EP89108850A patent/EP0342635B1/de not_active Expired - Lifetime
- 1989-05-17 DE DE68917517T patent/DE68917517T2/de not_active Expired - Fee Related
- 1989-05-17 AT AT89108850T patent/ATE110064T1/de not_active IP Right Cessation
- 1989-05-18 KR KR1019890006609A patent/KR900018058A/ko not_active Application Discontinuation
- 1989-05-18 ZA ZA893733A patent/ZA893733B/xx unknown
- 1989-05-18 JP JP1123007A patent/JP2824661B2/ja not_active Expired - Lifetime
- 1989-05-18 FI FI892388A patent/FI93955C/fi not_active IP Right Cessation
- 1989-05-18 PT PT90607A patent/PT90607B/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0342635B1 (de) | 1994-08-17 |
| FI892388A0 (fi) | 1989-05-18 |
| FI892388A (fi) | 1989-11-19 |
| NO177262C (no) | 1995-08-16 |
| IL90313A0 (en) | 1989-12-15 |
| JP2824661B2 (ja) | 1998-11-11 |
| KR900018058A (ko) | 1990-12-20 |
| NO891970D0 (no) | 1989-05-16 |
| NO177262B (no) | 1995-05-08 |
| DE68917517D1 (de) | 1994-09-22 |
| PT90607A (pt) | 1989-11-30 |
| CA1337123C (en) | 1995-09-26 |
| FI93955C (fi) | 1995-06-26 |
| FI93955B (fi) | 1995-03-15 |
| NO891970L (no) | 1989-11-20 |
| ATE110064T1 (de) | 1994-09-15 |
| AU3484589A (en) | 1989-11-23 |
| JPH0217158A (ja) | 1990-01-22 |
| NZ229136A (en) | 1992-01-29 |
| IE66016B1 (en) | 1995-11-29 |
| IE891533L (en) | 1989-11-18 |
| ZA893733B (en) | 1990-02-28 |
| ES2058383T3 (es) | 1994-11-01 |
| DE68917517T2 (de) | 1994-12-15 |
| DK270488D0 (da) | 1988-05-18 |
| US5039685A (en) | 1991-08-13 |
| EP0342635A1 (de) | 1989-11-23 |
| AU622178B2 (en) | 1992-04-02 |
| PT90607B (pt) | 1995-03-01 |
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