NO791648L - Fremgangsmaate ved fremstilling av nye kinazolinderivater - Google Patents
Fremgangsmaate ved fremstilling av nye kinazolinderivaterInfo
- Publication number
- NO791648L NO791648L NO791648A NO791648A NO791648L NO 791648 L NO791648 L NO 791648L NO 791648 A NO791648 A NO 791648A NO 791648 A NO791648 A NO 791648A NO 791648 L NO791648 L NO 791648L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- preparation
- lower alkyl
- chloroform
- piperidine
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 45
- 238000000034 method Methods 0.000 title claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 19
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- -1 1,2,3,4-tetrahydroisoquinolyl group Chemical group 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 7
- HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 description 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 239000002026 chloroform extract Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- KUBUQFFBRSHOMJ-UHFFFAOYSA-N benzyl 4-carbonochloridoylpiperidine-1-carboxylate Chemical compound C1CC(C(=O)Cl)CCN1C(=O)OCC1=CC=CC=C1 KUBUQFFBRSHOMJ-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000002808 molecular sieve Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- VKAOJUHYNXZMSM-UHFFFAOYSA-N 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidine-4-carboxylic acid Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCC(C(O)=O)CC1 VKAOJUHYNXZMSM-UHFFFAOYSA-N 0.000 description 3
- OVMWUKRHJWOARR-UHFFFAOYSA-N 2-(1-benzylpiperidin-4-yl)oxyacetic acid Chemical compound C1CC(OCC(=O)O)CCN1CC1=CC=CC=C1 OVMWUKRHJWOARR-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- GKCROKLQKJMQMJ-UHFFFAOYSA-N n-butylpiperidine-4-carboxamide Chemical compound CCCCNC(=O)C1CCNCC1 GKCROKLQKJMQMJ-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- BPPZXJZYCOETDA-UHFFFAOYSA-N 1-benzylpiperidin-4-ol Chemical compound C1CC(O)CCN1CC1=CC=CC=C1 BPPZXJZYCOETDA-UHFFFAOYSA-N 0.000 description 2
- KTWOATDVMCBOKL-UHFFFAOYSA-N 2-(2-piperidin-4-yloxyphenyl)acetic acid;hydrochloride Chemical compound Cl.OC(=O)CC1=CC=CC=C1OC1CCNCC1 KTWOATDVMCBOKL-UHFFFAOYSA-N 0.000 description 2
- RWLHOWNQSKSYQE-UHFFFAOYSA-N 2-[1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-4-yl]acetic acid Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCC(CC(O)=O)CC1 RWLHOWNQSKSYQE-UHFFFAOYSA-N 0.000 description 2
- LSUKBNPACYNGME-UHFFFAOYSA-N 2-[1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-4-yl]acetic acid;hydrochloride Chemical compound Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCC(CC(O)=O)CC1 LSUKBNPACYNGME-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000012223 aqueous fraction Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- BNROHLKYMKJZLM-UHFFFAOYSA-N ethyl 2-[2-(1-acetylpiperidin-4-yl)oxyphenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC=C1OC1CCN(C(C)=O)CC1 BNROHLKYMKJZLM-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- CCPJDOCBIGOOSL-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]piperidine-4-carboxamide Chemical compound COC1=CC(OC)=CC=C1CNC(=O)C1CCNCC1 CCPJDOCBIGOOSL-UHFFFAOYSA-N 0.000 description 2
- YXJXOPXCTGLNEU-UHFFFAOYSA-N n-butylpiperidine-3-carboxamide Chemical compound CCCCNC(=O)C1CCCNC1 YXJXOPXCTGLNEU-UHFFFAOYSA-N 0.000 description 2
- FICKGLKQSSSVOL-UHFFFAOYSA-N n-ethyl-2-piperidin-4-yloxyacetamide Chemical compound CCNC(=O)COC1CCNCC1 FICKGLKQSSSVOL-UHFFFAOYSA-N 0.000 description 2
- AKQIYQXGTBXWND-UHFFFAOYSA-N n-phenylpiperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NC1=CC=CC=C1 AKQIYQXGTBXWND-UHFFFAOYSA-N 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- JIYLLYLKTJCEEL-UHFFFAOYSA-N piperidin-4-yl n-ethylcarbamate Chemical compound CCNC(=O)OC1CCNCC1 JIYLLYLKTJCEEL-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 150000003246 quinazolines Chemical class 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000003756 stirring Methods 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
- 238000005406 washing Methods 0.000 description 2
- JJBRJULVZMWIIN-UHFFFAOYSA-N (1-benzylpiperidin-4-yl) n-ethylcarbamate Chemical compound C1CC(OC(=O)NCC)CCN1CC1=CC=CC=C1 JJBRJULVZMWIIN-UHFFFAOYSA-N 0.000 description 1
- SJUKJZSTBBSGHF-UHFFFAOYSA-N (2,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1Cl SJUKJZSTBBSGHF-UHFFFAOYSA-N 0.000 description 1
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 1
- PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- CDODQHDLKPYUNF-UHFFFAOYSA-N 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-n-(2-phenylethyl)piperidine-4-carboxamide;hydrochloride Chemical compound Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCC1C(=O)NCCC1=CC=CC=C1 CDODQHDLKPYUNF-UHFFFAOYSA-N 0.000 description 1
- DBVQOYBFSCTHFA-UHFFFAOYSA-N 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-n-butylpiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1CC(C(=O)NCCCC)CCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 DBVQOYBFSCTHFA-UHFFFAOYSA-N 0.000 description 1
- YJIAESRSIHOENT-UHFFFAOYSA-N 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-n-propylpiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1CC(C(=O)NCCC)CCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 YJIAESRSIHOENT-UHFFFAOYSA-N 0.000 description 1
- GXGDEVBYKYSNJQ-UHFFFAOYSA-N 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidine-4-carboxylic acid;hydrate Chemical compound O.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCC(C(O)=O)CC1 GXGDEVBYKYSNJQ-UHFFFAOYSA-N 0.000 description 1
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- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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- MXYCDYYIUYHPNP-UHFFFAOYSA-N methyl 2-(1-benzylpiperidin-4-yl)oxyacetate Chemical compound C1CC(OCC(=O)OC)CCN1CC1=CC=CC=C1 MXYCDYYIUYHPNP-UHFFFAOYSA-N 0.000 description 1
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- SGUNZEMSKPUFDM-UHFFFAOYSA-N n-(2-hydroxyethyl)piperidine-4-carboxamide Chemical compound OCCNC(=O)C1CCNCC1 SGUNZEMSKPUFDM-UHFFFAOYSA-N 0.000 description 1
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- KCGJGWKYMLRMOM-UHFFFAOYSA-N n-benzyl-n-methylpiperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)N(C)CC1=CC=CC=C1 KCGJGWKYMLRMOM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- RBRLJZFEYXKJEJ-UHFFFAOYSA-N n-butyl-2-piperidin-4-yloxyacetamide Chemical compound CCCCNC(=O)COC1CCNCC1 RBRLJZFEYXKJEJ-UHFFFAOYSA-N 0.000 description 1
- NAYREFLTLFLRQG-UHFFFAOYSA-N n-butyl-2-piperidin-4-yloxyacetamide;hydrochloride Chemical compound Cl.CCCCNC(=O)COC1CCNCC1 NAYREFLTLFLRQG-UHFFFAOYSA-N 0.000 description 1
- ZGJYDNSUCSSKMU-UHFFFAOYSA-N n-butylpyridine-3-carboxamide Chemical compound CCCCNC(=O)C1=CC=CN=C1 ZGJYDNSUCSSKMU-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- FCTZHFATVFONMW-UHFFFAOYSA-N n-phenylpyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)NC1=CC=CC=C1 FCTZHFATVFONMW-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical class OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- ROFVJSWBDQUQGW-UHFFFAOYSA-N piperidin-1-ium;bromide Chemical compound Br.C1CCNCC1 ROFVJSWBDQUQGW-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 1
- RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2035178 | 1978-05-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO791648L true NO791648L (no) | 1979-11-20 |
Family
ID=10144517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO791648A NO791648L (no) | 1978-05-18 | 1979-05-16 | Fremgangsmaate ved fremstilling av nye kinazolinderivater |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US4243666A (nl) |
| JP (1) | JPS554370A (nl) |
| AR (2) | AR223487A1 (nl) |
| AT (1) | ATA363379A (nl) |
| AU (1) | AU512947B2 (nl) |
| BE (1) | BE876297A (nl) |
| CA (1) | CA1240325A (nl) |
| CH (1) | CH643553A5 (nl) |
| CS (1) | CS214796B2 (nl) |
| DD (1) | DD143613A5 (nl) |
| DE (1) | DE2919800A1 (nl) |
| DK (1) | DK159079A (nl) |
| ES (2) | ES480671A1 (nl) |
| FI (1) | FI64589C (nl) |
| FR (1) | FR2434162A1 (nl) |
| GR (1) | GR72824B (nl) |
| HU (1) | HU182562B (nl) |
| IL (1) | IL57297A (nl) |
| IN (1) | IN153045B (nl) |
| IT (1) | IT1114222B (nl) |
| LU (1) | LU81284A1 (nl) |
| NL (1) | NL172157C (nl) |
| NO (1) | NO791648L (nl) |
| NZ (1) | NZ190465A (nl) |
| PH (1) | PH14802A (nl) |
| PL (2) | PL121158B1 (nl) |
| PT (1) | PT69622A (nl) |
| SE (1) | SE439306B (nl) |
| YU (2) | YU115279A (nl) |
| ZA (1) | ZA792390B (nl) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607034A (en) * | 1979-10-29 | 1986-08-19 | Mitsubishi Yuka Pharmaceutical Co., Ltd. | Quinazoline derivatives and pharmaceutical composition thereof |
| JPS5962766U (ja) * | 1982-06-30 | 1984-04-25 | 守田 智 | 小動物用給水器 |
| GB8414518D0 (en) * | 1984-06-07 | 1984-07-11 | Pfizer Ltd | Therapeutic agents |
| US5801195A (en) * | 1994-12-30 | 1998-09-01 | Celgene Corporation | Immunotherapeutic aryl amides |
| US6248888B1 (en) | 1997-11-14 | 2001-06-19 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of terazosin hydrochloride dihydrate |
| KR20030069218A (ko) * | 2001-01-18 | 2003-08-25 | 다케다 야쿠힌 고교 가부시키가이샤 | 벤질피페리딘 화합물의 제조 방법 |
| US6746460B2 (en) * | 2002-08-07 | 2004-06-08 | Satiety, Inc. | Intra-gastric fastening devices |
| WO2005042501A1 (en) * | 2003-11-03 | 2005-05-12 | Warner-Lambert Company Llc | Novel norepinephrine reuptake inhibitors for the treatment of central nervous system disorders |
| AR063275A1 (es) * | 2006-10-12 | 2009-01-14 | Epix Delaware Inc | Compuestos de carboxamida, una composicion farmaceutica que los comprende y su uso en la preparacion de un medicamento para el tratamiento de enfermedades mediadas por la activacion de ccr2. |
| KR20140069232A (ko) * | 2007-04-04 | 2014-06-09 | 시플라 리미티드 | 에르로티닙 및 그의 약학적으로 허용가능한 염의 제조방법 |
| KR20100102646A (ko) * | 2007-12-11 | 2010-09-24 | 가부시키가이샤 사이토파스파인더 | 카르복스아미드 화합물 및 케모카인 수용체 길항제로서의 이의 용도 |
| MX2011004295A (es) * | 2008-11-14 | 2011-05-23 | Hoffmann La Roche | Derivados de quinazolina como antagonistas del receptor de neurocinina 3 (nk3). |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1156973A (en) * | 1965-07-06 | 1969-07-02 | Quinazoline Derivatives | |
| US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
| FR2321890A1 (fr) * | 1975-08-26 | 1977-03-25 | Synthelabo | Nouveaux derives de la quinazoline, leurs sels, leur preparation et les medicaments qui en renferment |
| DK140695C (da) * | 1976-05-07 | 1980-05-12 | Synthelabo | Analogifremgangsmaade til fremstilling af 2,4-diamino-6,7-dimethoxyquinazolinderivater eller syreadditionssalte heraf |
-
1979
- 1979-04-18 DK DK159079A patent/DK159079A/da not_active IP Right Cessation
- 1979-05-14 US US06/038,509 patent/US4243666A/en not_active Expired - Lifetime
- 1979-05-16 AR AR276536A patent/AR223487A1/es active
- 1979-05-16 IT IT22720/79A patent/IT1114222B/it active
- 1979-05-16 AU AU47101/79A patent/AU512947B2/en not_active Ceased
- 1979-05-16 PL PL1979223844A patent/PL121158B1/pl unknown
- 1979-05-16 CS CS793372A patent/CS214796B2/cs unknown
- 1979-05-16 GR GR59104A patent/GR72824B/el unknown
- 1979-05-16 AT AT0363379A patent/ATA363379A/de not_active IP Right Cessation
- 1979-05-16 YU YU01152/79A patent/YU115279A/xx unknown
- 1979-05-16 DE DE19792919800 patent/DE2919800A1/de not_active Ceased
- 1979-05-16 BE BE0/195197A patent/BE876297A/xx unknown
- 1979-05-16 NO NO791648A patent/NO791648L/no unknown
- 1979-05-16 PL PL1979215626A patent/PL120651B1/pl unknown
- 1979-05-16 NL NLAANVRAGE7903853,A patent/NL172157C/nl not_active IP Right Cessation
- 1979-05-16 IL IL57297A patent/IL57297A/xx unknown
- 1979-05-16 IN IN337/DEL/79A patent/IN153045B/en unknown
- 1979-05-16 NZ NZ190465A patent/NZ190465A/xx unknown
- 1979-05-16 PH PH22500A patent/PH14802A/en unknown
- 1979-05-16 FI FI791562A patent/FI64589C/fi not_active IP Right Cessation
- 1979-05-17 CH CH459879A patent/CH643553A5/de not_active IP Right Cessation
- 1979-05-17 JP JP6100079A patent/JPS554370A/ja active Granted
- 1979-05-17 CA CA000327839A patent/CA1240325A/en not_active Expired
- 1979-05-17 FR FR7912635A patent/FR2434162A1/fr active Granted
- 1979-05-17 SE SE7904358A patent/SE439306B/sv not_active IP Right Cessation
- 1979-05-17 HU HU79PI678A patent/HU182562B/hu unknown
- 1979-05-17 ZA ZA792390A patent/ZA792390B/xx unknown
- 1979-05-17 LU LU81284A patent/LU81284A1/fr unknown
- 1979-05-17 PT PT69622A patent/PT69622A/pt unknown
- 1979-05-17 ES ES480671A patent/ES480671A1/es not_active Expired
- 1979-05-18 DD DD79213010A patent/DD143613A5/de unknown
-
1980
- 1980-02-01 ES ES488210A patent/ES488210A0/es active Granted
- 1980-10-28 AR AR283021A patent/AR224784A1/es active
-
1982
- 1982-11-16 YU YU02563/82A patent/YU256382A/xx unknown
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