NO860458L - Antihypertensive dihydropyridinderivater. - Google Patents
Antihypertensive dihydropyridinderivater.Info
- Publication number
- NO860458L NO860458L NO860458A NO860458A NO860458L NO 860458 L NO860458 L NO 860458L NO 860458 A NO860458 A NO 860458A NO 860458 A NO860458 A NO 860458A NO 860458 L NO860458 L NO 860458L
- Authority
- NO
- Norway
- Prior art keywords
- dimethyl
- formula
- compound
- dihydropyridine
- integer
- Prior art date
Links
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title description 11
- 230000003276 anti-hypertensive effect Effects 0.000 title description 6
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 235
- 238000002360 preparation method Methods 0.000 claims description 51
- -1 -CF 3 Inorganic materials 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000012546 transfer Methods 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 4
- RUIBFMSUYQMTCH-UHFFFAOYSA-N 5-o-[3-[4-(2,3-dihydroxypropoxy)phenyl]propyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCC=2C=CC(OCC(O)CO)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 RUIBFMSUYQMTCH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- QLNAYPDWIWUVHP-UHFFFAOYSA-N 5-o-[2-[4-(2,3-dihydroxypropoxy)phenyl]ethyl] 3-o-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCC=2C=CC(OCC(O)CO)=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 QLNAYPDWIWUVHP-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- 239000000203 mixture Substances 0.000 description 42
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 206010020772 Hypertension Diseases 0.000 description 10
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- 239000011734 sodium Substances 0.000 description 10
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- 206010027599 migraine Diseases 0.000 description 8
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- 208000024172 Cardiovascular disease Diseases 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
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- JPXPPUOCSLMCHK-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 JPXPPUOCSLMCHK-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
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- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 6
- 230000000747 cardiac effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 6
- 230000035488 systolic blood pressure Effects 0.000 description 6
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- XIJKESJZCRJVQU-ZGTCLIOFSA-N methyl (2R)-2-amino-2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]phenyl]acetate Chemical compound CC1(OCC(O1)CC1=CC=C(C=C1)[C@H](C(=O)OC)N)C XIJKESJZCRJVQU-ZGTCLIOFSA-N 0.000 description 1
- XIJKESJZCRJVQU-ABLWVSNPSA-N methyl (2S)-2-amino-2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]phenyl]acetate Chemical compound CC1(OCC(O1)CC1=CC=C(C=C1)[C@@H](C(=O)OC)N)C XIJKESJZCRJVQU-ABLWVSNPSA-N 0.000 description 1
- ZZOFQADXQGOJCQ-KZUDCZAMSA-N methyl (2S)-2-amino-2-[4-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl]phenyl]acetate Chemical compound CC1(OCC(O1)CCC1=CC=C(C=C1)[C@@H](C(=O)OC)N)C ZZOFQADXQGOJCQ-KZUDCZAMSA-N 0.000 description 1
- TVIVLENJTXGRAM-UHFFFAOYSA-N methyl 2-(4-aminophenyl)acetate Chemical compound COC(=O)CC1=CC=C(N)C=C1 TVIVLENJTXGRAM-UHFFFAOYSA-N 0.000 description 1
- OWZKPLVEECROKR-UHFFFAOYSA-N methyl 2-(4-benzylsulfanylphenyl)acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCC1=CC=CC=C1 OWZKPLVEECROKR-UHFFFAOYSA-N 0.000 description 1
- JWDUTVWAWSXXOK-UHFFFAOYSA-N methyl 2-[4-(2-phenylmethoxyethoxy)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCCOCC1=CC=CC=C1 JWDUTVWAWSXXOK-UHFFFAOYSA-N 0.000 description 1
- MFTWQODRAPNZJX-UHFFFAOYSA-N methyl 2-[4-(2-phenylmethoxyethylamino)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCCOCC1=CC=CC=C1 MFTWQODRAPNZJX-UHFFFAOYSA-N 0.000 description 1
- MWYNGQHAWPSRPG-UHFFFAOYSA-N methyl 2-[4-(2-phenylmethoxyethylsulfanyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCCOCC1=CC=CC=C1 MWYNGQHAWPSRPG-UHFFFAOYSA-N 0.000 description 1
- YEKMVILFPFCZMZ-UHFFFAOYSA-N methyl 2-[4-(2-phenylmethoxyethylsulfinyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)CCOCC1=CC=CC=C1 YEKMVILFPFCZMZ-UHFFFAOYSA-N 0.000 description 1
- PQYFRCAUJZINRB-UHFFFAOYSA-N methyl 2-[4-(2-phenylmethoxyethylsulfonyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CCOCC1=CC=CC=C1 PQYFRCAUJZINRB-UHFFFAOYSA-N 0.000 description 1
- YXWXXNQVCFGQCJ-UHFFFAOYSA-N methyl 2-[4-(3-phenylmethoxypropoxy)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCCCOCC1=CC=CC=C1 YXWXXNQVCFGQCJ-UHFFFAOYSA-N 0.000 description 1
- BGCAPZJEQMKYKE-UHFFFAOYSA-N methyl 2-[4-(3-phenylmethoxypropylamino)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCCCOCC1=CC=CC=C1 BGCAPZJEQMKYKE-UHFFFAOYSA-N 0.000 description 1
- IZMUEJFAHUKHCV-UHFFFAOYSA-N methyl 2-[4-(3-phenylmethoxypropylsulfanyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCCCOCC1=CC=CC=C1 IZMUEJFAHUKHCV-UHFFFAOYSA-N 0.000 description 1
- IABXBNFLMYHNGP-UHFFFAOYSA-N methyl 2-[4-(3-phenylmethoxypropylsulfinyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)CCCOCC1=CC=CC=C1 IABXBNFLMYHNGP-UHFFFAOYSA-N 0.000 description 1
- IPKXCKWVJWJYCJ-UHFFFAOYSA-N methyl 2-[4-(3-phenylmethoxypropylsulfonyl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CCCOCC1=CC=CC=C1 IPKXCKWVJWJYCJ-UHFFFAOYSA-N 0.000 description 1
- QRFYUJKODSBRSA-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxan-5-yl)methylamino]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCC1COC(C)(C)OC1 QRFYUJKODSBRSA-UHFFFAOYSA-N 0.000 description 1
- ZKEJDVOPESIWBI-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxan-5-yl)methylsulfanyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCC1COC(C)(C)OC1 ZKEJDVOPESIWBI-UHFFFAOYSA-N 0.000 description 1
- ZPUDFNHNQJNIIZ-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxan-5-yl)methylsulfinyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)CC1COC(C)(C)OC1 ZPUDFNHNQJNIIZ-UHFFFAOYSA-N 0.000 description 1
- FECGERPFJNUMFG-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxan-5-yl)methylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CC1COC(C)(C)OC1 FECGERPFJNUMFG-UHFFFAOYSA-N 0.000 description 1
- FRZLGNRHFJXJEC-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxan-5-yl)oxymethyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1COC1COC(C)(C)OC1 FRZLGNRHFJXJEC-UHFFFAOYSA-N 0.000 description 1
- VBJIMULQPJGODN-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methylsulfanyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCC1OC(C)(C)OC1 VBJIMULQPJGODN-UHFFFAOYSA-N 0.000 description 1
- DIMOMADICYFQDJ-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methylsulfinyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)CC1OC(C)(C)OC1 DIMOMADICYFQDJ-UHFFFAOYSA-N 0.000 description 1
- MWMMSJWPFQDINJ-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CC1OC(C)(C)OC1 MWMMSJWPFQDINJ-UHFFFAOYSA-N 0.000 description 1
- OMJPUCBGISGZFR-OGDGHAERSA-N methyl 2-[4-[(s)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethylsulfinyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1[S@@](=O)CCC1OC(C)(C)OC1 OMJPUCBGISGZFR-OGDGHAERSA-N 0.000 description 1
- WPONMTPOLSIUAQ-UHFFFAOYSA-N methyl 2-[4-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCCC1OC(C)(C)OC1 WPONMTPOLSIUAQ-UHFFFAOYSA-N 0.000 description 1
- BQDJONFNVRHXGF-UHFFFAOYSA-N methyl 2-[4-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethylamino]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCCC1OC(C)(C)OC1 BQDJONFNVRHXGF-UHFFFAOYSA-N 0.000 description 1
- XDDPNQFCKZMMHV-UHFFFAOYSA-N methyl 2-[4-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethylsulfanyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCCC1OC(C)(C)OC1 XDDPNQFCKZMMHV-UHFFFAOYSA-N 0.000 description 1
- UOCBQXXJWDSMQP-UHFFFAOYSA-N methyl 2-[4-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CCC1OC(C)(C)OC1 UOCBQXXJWDSMQP-UHFFFAOYSA-N 0.000 description 1
- WPONMTPOLSIUAQ-AWEZNQCLSA-N methyl 2-[4-[2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCC[C@@H]1OC(C)(C)OC1 WPONMTPOLSIUAQ-AWEZNQCLSA-N 0.000 description 1
- ZFNHBTNMGVFLDL-UHFFFAOYSA-N methyl 2-[4-[3-(2,2-dimethyl-1,3-dioxolan-4-yl)propoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCCCC1OC(C)(C)OC1 ZFNHBTNMGVFLDL-UHFFFAOYSA-N 0.000 description 1
- PQKUWZHDYAFQLR-UHFFFAOYSA-N methyl 2-[4-[3-(2,2-dimethyl-1,3-dioxolan-4-yl)propylamino]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCCCC1OC(C)(C)OC1 PQKUWZHDYAFQLR-UHFFFAOYSA-N 0.000 description 1
- NULSDCJDGXAXAX-UHFFFAOYSA-N methyl 2-[4-[3-(2,2-dimethyl-1,3-dioxolan-4-yl)propylsulfanyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCCCC1OC(C)(C)OC1 NULSDCJDGXAXAX-UHFFFAOYSA-N 0.000 description 1
- SMPMKFYBGCOCJB-UHFFFAOYSA-N methyl 2-[4-[3-(2,2-dimethyl-1,3-dioxolan-4-yl)propylsulfinyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)CCCC1OC(C)(C)OC1 SMPMKFYBGCOCJB-UHFFFAOYSA-N 0.000 description 1
- XOJYCSMEVVHAQO-UHFFFAOYSA-N methyl 2-[4-[3-(2,2-dimethyl-1,3-dioxolan-4-yl)propylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CCCC1OC(C)(C)OC1 XOJYCSMEVVHAQO-UHFFFAOYSA-N 0.000 description 1
- HPEVCLXFXXGKAJ-CYBMUJFWSA-N methyl 2-[4-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OC[C@H]1OC(C)(C)OC1 HPEVCLXFXXGKAJ-CYBMUJFWSA-N 0.000 description 1
- MWMMSJWPFQDINJ-GFCCVEGCSA-N methyl 2-[4-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)C[C@@H]1OC(C)(C)OC1 MWMMSJWPFQDINJ-GFCCVEGCSA-N 0.000 description 1
- HPEVCLXFXXGKAJ-ZDUSSCGKSA-N methyl 2-[4-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OC[C@@H]1OC(C)(C)OC1 HPEVCLXFXXGKAJ-ZDUSSCGKSA-N 0.000 description 1
- IDRZVTGCEKHCRR-JTQLQIEISA-N methyl 2-[4-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]thiophen-2-yl]acetate Chemical compound CC1(OC[C@@H](O1)CC=1C=C(SC=1)CC(=O)OC)C IDRZVTGCEKHCRR-JTQLQIEISA-N 0.000 description 1
- JBZKKAUFTNAINA-UHFFFAOYSA-N methyl 2-[4-[[2,2-dimethyl-5-(phenylmethoxymethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCC1C(COCC=2C=CC=CC=2)OC(C)(C)O1 JBZKKAUFTNAINA-UHFFFAOYSA-N 0.000 description 1
- OXDSKYGAQBTFRL-UHFFFAOYSA-N methyl 2-[4-[[2,2-dimethyl-5-(phenylmethoxymethyl)-1,3-dioxolan-4-yl]methylamino]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1NCC1C(COCC=2C=CC=CC=2)OC(C)(C)O1 OXDSKYGAQBTFRL-UHFFFAOYSA-N 0.000 description 1
- TWCVUBVTJZKUKV-UHFFFAOYSA-N methyl 2-[4-[[2,2-dimethyl-5-(phenylmethoxymethyl)-1,3-dioxolan-4-yl]methylsulfanyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1SCC1C(COCC=2C=CC=CC=2)OC(C)(C)O1 TWCVUBVTJZKUKV-UHFFFAOYSA-N 0.000 description 1
- NXCCVODNZUVDDS-UHFFFAOYSA-N methyl 2-[4-[[2,2-dimethyl-5-(phenylmethoxymethyl)-1,3-dioxolan-4-yl]methylsulfonyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)CC1C(COCC=2C=CC=CC=2)OC(C)(C)O1 NXCCVODNZUVDDS-UHFFFAOYSA-N 0.000 description 1
- XIJKESJZCRJVQU-UHFFFAOYSA-N methyl 2-amino-2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]phenyl]acetate Chemical compound C1=CC(C(N)C(=O)OC)=CC=C1CC1OC(C)(C)OC1 XIJKESJZCRJVQU-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- KLUYEWUNEYJQDC-UHFFFAOYSA-N methyl 3-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCC1OC(C)(C)OC1 KLUYEWUNEYJQDC-UHFFFAOYSA-N 0.000 description 1
- UZHISWLCHOMTIO-UHFFFAOYSA-N methyl 4-(4-hydroxyphenyl)butanoate Chemical compound COC(=O)CCCC1=CC=C(O)C=C1 UZHISWLCHOMTIO-UHFFFAOYSA-N 0.000 description 1
- MXOCZJKMELIXSG-UHFFFAOYSA-N methyl 4-[(4-methylphenyl)methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OCC1=CC=C(C)C=C1 MXOCZJKMELIXSG-UHFFFAOYSA-N 0.000 description 1
- AHRVBVXGIXUOBR-UHFFFAOYSA-N methyl 5-carbonochloridoyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(Cl)=O)C1C1=CC=CC([N+]([O-])=O)=C1 AHRVBVXGIXUOBR-UHFFFAOYSA-N 0.000 description 1
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 description 1
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 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
- LVAACBVNZRPHFE-UHFFFAOYSA-N tert-butyl n-[4-(2-hydroxyethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(CCO)C=C1 LVAACBVNZRPHFE-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- HGQNJGQFRHILER-UHFFFAOYSA-N triethyl 3-[4-(hydroxymethyl)phenyl]propane-1,1,1-tricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)(C(=O)OCC)CCC1=CC=C(CO)C=C1 HGQNJGQFRHILER-UHFFFAOYSA-N 0.000 description 1
- JRBUQUSCUXJMSX-UHFFFAOYSA-N triethyl 3-[4-[4-[5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxybutyl]phenyl]propane-1,1,1-tricarboxylate Chemical compound C1=CC(CCC(C(=O)OCC)(C(=O)OCC)C(=O)OCC)=CC=C1CCCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 JRBUQUSCUXJMSX-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000001521 two-tailed test Methods 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005303 weighing Methods 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
- C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
- C07D211/84—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 two 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 directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero 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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
- C07D211/84—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 two 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 directly attached to ring carbon atoms
- C07D211/90—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
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/20—Free hydroxyl or mercaptan
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/24—Radicals substituted by singly bound oxygen or sulfur atoms esterified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/700,439 US4595690A (en) | 1985-02-11 | 1985-02-11 | Antihypertensive dihydropyridine derivatives |
US06/808,401 US4672071A (en) | 1985-02-11 | 1985-12-12 | Antihypertensive dihydropyridine compositions, optical isomers and intermediates |
Publications (1)
Publication Number | Publication Date |
---|---|
NO860458L true NO860458L (no) | 1986-08-12 |
Family
ID=27106619
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO860458A NO860458L (no) | 1985-02-11 | 1986-02-10 | Antihypertensive dihydropyridinderivater. |
Country Status (15)
Country | Link |
---|---|
US (1) | US4672071A (hu) |
EP (1) | EP0191448A3 (hu) |
JP (1) | JPS61210071A (hu) |
KR (1) | KR860006442A (hu) |
AU (1) | AU591093B2 (hu) |
DK (1) | DK64286A (hu) |
ES (2) | ES8708130A1 (hu) |
FI (1) | FI860584A (hu) |
GR (1) | GR860384B (hu) |
HU (2) | HU198019B (hu) |
IL (1) | IL77843A (hu) |
NO (1) | NO860458L (hu) |
PH (1) | PH22806A (hu) |
PL (1) | PL257890A1 (hu) |
PT (1) | PT81987B (hu) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2576843A (en) * | 1944-12-30 | 1951-11-27 | Rosenblads Patenter Ab | Heat exchange apparatus |
US2788065A (en) * | 1950-08-14 | 1957-04-09 | Rosenblads Patenter Ab | Surface type evaporator employing channel switching for cleaning purposes |
US4814455A (en) * | 1986-04-16 | 1989-03-21 | Bristol-Myers Company | Dihydro-3,5-dicarboxylates |
JPH0686429B2 (ja) * | 1986-08-27 | 1994-11-02 | 株式会社ミドリ十字 | ジヒドロピリジン誘導体 |
US4886819A (en) * | 1986-08-27 | 1989-12-12 | The Green Cross Corporation | Dihydropyridine derivatives and pharmaceutical composition thereof |
DE3633496A1 (de) * | 1986-10-02 | 1988-04-14 | Hoechst Ag | Kombination von angiotensin-converting-enzyme-hemmern mit calciumantagonisten sowie deren verwendung in arzneimitteln |
US4920225A (en) * | 1986-12-22 | 1990-04-24 | Laboratoires Syntex S.A. | Resolution of 1,4-dihydropyridine derivatives |
US5576439A (en) * | 1994-10-28 | 1996-11-19 | Ciba-Geigy Corporation | Dihydropyridinecarboxylic acid anhydrides |
SE9801990D0 (sv) * | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl propionic acid derivatives and analogs |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4031104A (en) * | 1972-04-18 | 1977-06-21 | Bayer Aktiengesellschaft | 1,4-Dihydropyridine carboxylic acid esters |
CH583702A5 (en) * | 1973-02-13 | 1977-01-14 | Science Union & Cie | Anti-hypertensive dihydropyridines - 4-aryl 2,5-dihydropyridine 3,5-dicarboxylic esters |
US3985758A (en) * | 1973-02-20 | 1976-10-12 | Yamanouchi Pharmaceutical Co., Ltd. | 1,4-Dihydropyridine derivatives |
DE2508181A1 (de) * | 1975-02-26 | 1976-09-09 | Bayer Ag | 1,4-dihydropyridincarbonsaeurearal- kylester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
US4154839A (en) * | 1975-11-05 | 1979-05-15 | Bayer Aktiengesellschaft | 2,6-Dimethyl-3-carboxymethoxy-4-(2-nitrophenyl)-5-carbisobutoxy-1,4-dihydropyridine |
DE2639498A1 (de) * | 1976-09-02 | 1978-03-09 | Bayer Ag | Neue schwefelhaltige amino-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
DK161312C (da) * | 1982-03-11 | 1991-12-09 | Pfizer | Analogifremgangsmaade til fremstilling af 2-aminoalkoxymethyl-4-phenyl-6-methyl-1,4-dihydropyridin-3,5-dicarboxylsyreestere eller syreadditionssalte deraf samt phthalimidoderivater til anvendelse som udgangsmateriale ved fremgangsmaaden |
US4656181A (en) * | 1982-11-24 | 1987-04-07 | Cermol S.A. | Esters of 1,4-dihydropyridines, processes for the preparation of the new esters, and medicaments containing the same |
JPS60120861A (ja) * | 1983-12-02 | 1985-06-28 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体 |
GB8503426D0 (en) * | 1985-02-11 | 1985-03-13 | Ici Plc | Pyridine derivatives |
US4595690A (en) * | 1985-02-11 | 1986-06-17 | Syntex (U.S.A.) Inc. | Antihypertensive dihydropyridine derivatives |
-
1985
- 1985-02-10 IL IL77843A patent/IL77843A/xx unknown
- 1985-12-12 US US06/808,401 patent/US4672071A/en not_active Expired - Fee Related
-
1986
- 1986-02-07 PT PT81987A patent/PT81987B/pt unknown
- 1986-02-10 NO NO860458A patent/NO860458L/no unknown
- 1986-02-10 FI FI860584A patent/FI860584A/fi not_active Application Discontinuation
- 1986-02-10 AU AU53363/86A patent/AU591093B2/en not_active Ceased
- 1986-02-10 HU HU86541A patent/HU198019B/hu not_active IP Right Cessation
- 1986-02-10 PL PL25789086A patent/PL257890A1/xx unknown
- 1986-02-10 EP EP86101674A patent/EP0191448A3/en not_active Ceased
- 1986-02-10 ES ES551809A patent/ES8708130A1/es not_active Expired
- 1986-02-10 PH PH33402A patent/PH22806A/en unknown
- 1986-02-10 DK DK64286A patent/DK64286A/da not_active Application Discontinuation
- 1986-02-10 KR KR1019860000900A patent/KR860006442A/ko not_active Application Discontinuation
- 1986-02-10 HU HU861987A patent/HU198478B/hu unknown
- 1986-02-10 JP JP61027735A patent/JPS61210071A/ja active Pending
- 1986-02-11 GR GR860384A patent/GR860384B/el unknown
-
1987
- 1987-07-16 ES ES557628A patent/ES8802449A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
ES557628A0 (es) | 1988-07-01 |
EP0191448A3 (en) | 1987-08-19 |
AU591093B2 (en) | 1989-11-30 |
HUT41732A (en) | 1987-05-28 |
HUT44501A (en) | 1988-03-28 |
DK64286D0 (da) | 1986-02-10 |
HU198019B (en) | 1989-07-28 |
IL77843A (en) | 1989-07-31 |
HU198478B (en) | 1989-10-30 |
ES551809A0 (es) | 1987-10-16 |
FI860584A0 (fi) | 1986-02-10 |
PT81987A (en) | 1986-03-01 |
AU5336386A (en) | 1986-08-14 |
PH22806A (en) | 1988-12-27 |
ES8802449A1 (es) | 1988-07-01 |
PL257890A1 (en) | 1988-07-21 |
US4672071A (en) | 1987-06-09 |
JPS61210071A (ja) | 1986-09-18 |
EP0191448A2 (en) | 1986-08-20 |
PT81987B (en) | 1987-08-13 |
KR860006442A (ko) | 1986-09-11 |
ES8708130A1 (es) | 1987-10-16 |
FI860584A (fi) | 1986-08-12 |
DK64286A (da) | 1986-08-12 |
GR860384B (en) | 1986-05-09 |
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