JPS59139342A - ロイコトリエン「きつ」抗物質 - Google Patents
ロイコトリエン「きつ」抗物質Info
- Publication number
- JPS59139342A JPS59139342A JP58175237A JP17523783A JPS59139342A JP S59139342 A JPS59139342 A JP S59139342A JP 58175237 A JP58175237 A JP 58175237A JP 17523783 A JP17523783 A JP 17523783A JP S59139342 A JPS59139342 A JP S59139342A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- propylphenoxy
- acetyl
- acid
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003042 antagnostic effect Effects 0.000 title claims description 6
- 239000000126 substance Substances 0.000 title abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 288
- -1 C1-6 alkythio Chemical group 0.000 claims abstract description 77
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 36
- 150000002617 leukotrienes Chemical class 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
- 125000004429 atom Chemical group 0.000 claims abstract description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 15
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 14
- 125000005843 halogen group Chemical group 0.000 claims abstract description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 10
- 230000002378 acidificating effect Effects 0.000 claims abstract description 10
- 125000002252 acyl group Chemical group 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 229910052736 halogen Chemical group 0.000 claims abstract description 6
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 6
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003937 drug carrier Substances 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 117
- 239000011734 sodium Substances 0.000 claims description 59
- 229910052708 sodium Inorganic materials 0.000 claims description 56
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 32
- 238000003786 synthesis reaction Methods 0.000 claims description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
- 125000000457 gamma-lactone group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
- ZTGIHSPNBGGQOI-UHFFFAOYSA-N 4-(2,3-dimethylphenyl)butanoic acid Chemical compound CC1=CC=CC(CCCC(O)=O)=C1C ZTGIHSPNBGGQOI-UHFFFAOYSA-N 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 3
- NCAQWQHBWKKCJB-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]phenyl]-n-methylsulfonyl-4-oxobutanamide Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCC(=O)NS(C)(=O)=O)C=C1 NCAQWQHBWKKCJB-UHFFFAOYSA-N 0.000 claims description 2
- NFUQSLYHMGKZNN-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-oxobutanenitrile Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCC#N)C=C1 NFUQSLYHMGKZNN-UHFFFAOYSA-N 0.000 claims description 2
- KPQOOCVEKWNQOR-UHFFFAOYSA-N 5-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-3H-furan-2-one Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C=2OC(=O)CC=2)C=C1 KPQOOCVEKWNQOR-UHFFFAOYSA-N 0.000 claims description 2
- RZHLPXCWZXRTEC-UHFFFAOYSA-N 6-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-6-oxohexanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCCCC(O)=O)C=C1 RZHLPXCWZXRTEC-UHFFFAOYSA-N 0.000 claims description 2
- ZIPLUEXSCPLCEI-UHFFFAOYSA-N cyanamide group Chemical group C(#N)[NH-] ZIPLUEXSCPLCEI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 2
- YYHGNOXRCMENKZ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C=C1F YYHGNOXRCMENKZ-UHFFFAOYSA-N 0.000 claims 2
- QPGIXCNBLLJECT-UHFFFAOYSA-N 4-hydroxy-3-methyl-4-phenylbutanoic acid Chemical compound OC(=O)CC(C)C(O)C1=CC=CC=C1 QPGIXCNBLLJECT-UHFFFAOYSA-N 0.000 claims 2
- RNQKOGRFVUPYEJ-UHFFFAOYSA-N 4-[4-[2-[(4-acetyl-3-hydroxy-2-propylphenoxy)methyl]prop-2-enoxy]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(=C)COC1=CC=C(C(=O)CCC(O)=O)C=C1F RNQKOGRFVUPYEJ-UHFFFAOYSA-N 0.000 claims 1
- UUNPOKWNTZMLEW-UHFFFAOYSA-N 4-[4-[2-[(4-acetyl-3-hydroxy-2-propylphenoxy)methyl]prop-2-enoxy]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(=C)COC1=CC=C(C(=O)CCC(O)=O)C=C1 UUNPOKWNTZMLEW-UHFFFAOYSA-N 0.000 claims 1
- UWSWHNPCOXVTIB-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfanyl-2-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(O)CSC1=CC=C(C(=O)CCC(O)=O)C(F)=C1 UWSWHNPCOXVTIB-UHFFFAOYSA-N 0.000 claims 1
- CNNVXNCDEHBYQQ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfanyl-2-hydroxyphenyl]-4-oxobutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCC(O)CSC1=CC=C(C(=O)CCC(O)=O)C(O)=C1 CNNVXNCDEHBYQQ-UHFFFAOYSA-N 0.000 claims 1
- NFPSDVWNIUHHEZ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfonyl-2-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(O)CS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C(F)=C1 NFPSDVWNIUHHEZ-UHFFFAOYSA-N 0.000 claims 1
- MJWMWZFELIIXTM-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfonyl-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(O)CS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1F MJWMWZFELIIXTM-UHFFFAOYSA-N 0.000 claims 1
- OSCMCMCSUTZSPM-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropyl]sulfonylphenyl]-4-oxobutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCC(O)CS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1 OSCMCMCSUTZSPM-UHFFFAOYSA-N 0.000 claims 1
- AYCZZKXTWKEZDY-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-2-chlorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C(Cl)=C1 AYCZZKXTWKEZDY-UHFFFAOYSA-N 0.000 claims 1
- XFRWXILXSBRRHM-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-2-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C(F)=C1 XFRWXILXSBRRHM-UHFFFAOYSA-N 0.000 claims 1
- PBLQOVWNNHCABT-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3-chlorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C=C1Cl PBLQOVWNNHCABT-UHFFFAOYSA-N 0.000 claims 1
- JFABZGKGYKQRTP-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-3-methyl-4-oxobutanoic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCCCOC1=CC=C(C(=O)C(C)CC(O)=O)C=C1 JFABZGKGYKQRTP-UHFFFAOYSA-N 0.000 claims 1
- BLSHQCBWUWPDDJ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(C(=O)CCC(O)=O)C=C1 BLSHQCBWUWPDDJ-UHFFFAOYSA-N 0.000 claims 1
- QHKNHNZJOXJSCQ-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-2-hydroxyphenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCC(O)=O)C(O)=C1 QHKNHNZJOXJSCQ-UHFFFAOYSA-N 0.000 claims 1
- HEYIEJISYCVGPG-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCSC1=CC=C(C(=O)CCC(O)=O)C=C1F HEYIEJISYCVGPG-UHFFFAOYSA-N 0.000 claims 1
- QCKZVTHRYSFVFF-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylsulfanyl]-3-propylphenyl]-4-oxobutanoic acid Chemical compound CCCC1=CC(C(=O)CCC(O)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(O)=C1CCC QCKZVTHRYSFVFF-UHFFFAOYSA-N 0.000 claims 1
- OFJAABUKTKNXTI-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-3-hydroxy-2-propylphenyl)sulfanylpropoxy]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(=O)CCC(O)=O)C=C1F OFJAABUKTKNXTI-UHFFFAOYSA-N 0.000 claims 1
- IJJBWKVISPQRRY-UHFFFAOYSA-N 4-[4-[3-(4-acetyl-6-chloro-3-hydroxy-2-propylphenoxy)propylsulfonyl]phenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC(Cl)=C1OCCCS(=O)(=O)C1=CC=C(C(=O)CCC(O)=O)C=C1 IJJBWKVISPQRRY-UHFFFAOYSA-N 0.000 claims 1
- HLFMZKCMELQARE-UHFFFAOYSA-N 4-[4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)but-2-enoxy]-3-fluorophenyl]-4-oxobutanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC=CCOC1=CC=C(C(=O)CCC(O)=O)C=C1F HLFMZKCMELQARE-UHFFFAOYSA-N 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 5
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 3
- 239000005557 antagonist Substances 0.000 abstract description 3
- 229930195733 hydrocarbon Natural products 0.000 abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 abstract description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract description 2
- 150000003457 sulfones Chemical class 0.000 abstract description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
- 229910052717 sulfur Inorganic materials 0.000 abstract 3
- 238000006467 substitution reaction Methods 0.000 abstract 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
- 206010002198 Anaphylactic reaction Diseases 0.000 abstract 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 abstract 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 abstract 1
- 230000036783 anaphylactic response Effects 0.000 abstract 1
- 208000003455 anaphylaxis Diseases 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 150000003462 sulfoxides Chemical class 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- 150000003536 tetrazoles Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 130
- 239000000203 mixture Substances 0.000 description 113
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
- 239000000243 solution Substances 0.000 description 81
- 238000002844 melting Methods 0.000 description 67
- 230000008018 melting Effects 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- 238000000921 elemental analysis Methods 0.000 description 60
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 40
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 40
- 238000004587 chromatography analysis Methods 0.000 description 34
- 238000000034 method Methods 0.000 description 33
- 150000002148 esters Chemical class 0.000 description 32
- 239000000284 extract Substances 0.000 description 32
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 239000000741 silica gel Substances 0.000 description 29
- 229910002027 silica gel Inorganic materials 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 25
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 239000007787 solid Substances 0.000 description 18
- 239000007788 liquid Substances 0.000 description 17
- 150000004702 methyl esters Chemical class 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 11
- 150000002596 lactones Chemical group 0.000 description 11
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 10
- 239000012141 concentrate Substances 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- GMCUFZZWMZKWAC-UHFFFAOYSA-N 1-[4-(3-bromopropylsulfanyl)phenyl]-4-hydroxybutan-1-one Chemical compound OCCCC(=O)C1=CC=C(SCCCBr)C=C1 GMCUFZZWMZKWAC-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- 241000700198 Cavia Species 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
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- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/58—One oxygen atom, e.g. butenolide
-
- 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
- C07D317/32—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 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
- C07D317/34—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Furan Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42233882A | 1982-09-23 | 1982-09-23 | |
| US422338 | 1999-10-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS59139342A true JPS59139342A (ja) | 1984-08-10 |
Family
ID=23674451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58175237A Pending JPS59139342A (ja) | 1982-09-23 | 1983-09-24 | ロイコトリエン「きつ」抗物質 |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0104885B1 (enEXAMPLES) |
| JP (1) | JPS59139342A (enEXAMPLES) |
| KR (1) | KR840006336A (enEXAMPLES) |
| AT (1) | ATE20233T1 (enEXAMPLES) |
| AU (1) | AU557953B2 (enEXAMPLES) |
| CA (1) | CA1210770A (enEXAMPLES) |
| DE (1) | DE3363942D1 (enEXAMPLES) |
| DK (1) | DK432783A (enEXAMPLES) |
| ES (1) | ES525824A0 (enEXAMPLES) |
| GR (1) | GR79677B (enEXAMPLES) |
| IE (1) | IE55971B1 (enEXAMPLES) |
| IL (1) | IL69691A (enEXAMPLES) |
| NZ (1) | NZ205559A (enEXAMPLES) |
| PT (1) | PT77367B (enEXAMPLES) |
| ZA (1) | ZA837048B (enEXAMPLES) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5143931A (en) * | 1982-06-24 | 1992-09-01 | Smithkline Beecham Corporation | Leukotriene antagonists containing tetrazolyl groups |
| US5135940A (en) * | 1982-09-23 | 1992-08-04 | Merck Frosst Canada, Inc. | Leukotriene antagonists |
| EP0123541B1 (en) * | 1983-04-21 | 1987-07-22 | Merck Frosst Canada Inc. | Leukotriene antagonists |
| US4820867A (en) * | 1983-04-21 | 1989-04-11 | Merck Frosst Canada, Inc. | Phenoxypropoxy halophenylacetic acids as leukotriene antagonists |
| US4539419A (en) * | 1983-05-02 | 1985-09-03 | Hoffmann-La Roche Inc. | Naphthalenyloxy substituted carboxylic acids |
| EP0156233A3 (en) * | 1984-03-19 | 1986-02-19 | Merck & Co. Inc. | Use of leukotriene antagonists for producing cytoprotective pharmaceutical compositions and process for producing cytoprotective pharmaceutical compositions |
| US4939279A (en) * | 1985-04-19 | 1990-07-03 | Smithkline Beecham Corporation | Leukotriene antagonists |
| US4937253A (en) * | 1985-04-19 | 1990-06-26 | Smithkline Beecham Corporation | Ester prodrugs |
| DE3515278A1 (de) * | 1985-04-27 | 1986-10-30 | Grünenthal GmbH, 5190 Stolberg | Neue benzoesaeurederivate, diese enthaltende arzneimittel und verfahren zur herstellung dieser verbindungen und arzneimittel |
| CA1309557C (en) | 1985-06-18 | 1992-10-27 | Robert N. Young | Leukotriene antagonists |
| US4990526A (en) * | 1985-06-18 | 1991-02-05 | Merck Frosst Canada, Inc. | Leukotriene antagonists, compositions and methods of use thereof |
| ATE90076T1 (de) | 1986-03-27 | 1993-06-15 | Merck Frosst Canada Inc | Tetrahydrocarbazole ester. |
| US4857659A (en) * | 1986-04-28 | 1989-08-15 | Merck Frosst Canada, Inc. | Stereoselective synthesis of leukotriene antagonists |
| PT85110A (en) * | 1986-06-23 | 1987-07-01 | Merck Frosst Canada Inc | Process for preparing benzenealkanoic acid derivatives useful as leukotriene antagonists |
| GB8619956D0 (en) * | 1986-08-15 | 1986-09-24 | Roussel Lab Ltd | Chemical compounds |
| US4906658A (en) * | 1987-04-21 | 1990-03-06 | Merck Frosst Canada, Inc. | Fluoro-sulfones |
| PT87616B (pt) * | 1987-06-24 | 1992-09-30 | Smithkline Beecham Corp | Processo de preparacao de antagonistas do leucotrieno e de composicoes farmaceuticas |
| US4985585A (en) * | 1988-03-07 | 1991-01-15 | Kyorin Pharmaceutical Co., Ltd. | Phenoxyalkylcarboxylic acid derivatives and process for their preparations |
| US4954513A (en) * | 1988-12-23 | 1990-09-04 | Smithkline Beecham Corporation | Leukotriene antagonists |
| US5428033A (en) | 1990-10-12 | 1995-06-27 | Merck Frosst Canada, Inc. | Saturated hydroxyalkylquinoline acids as leukotriene antagonists |
| DE4228201A1 (de) * | 1992-08-25 | 1994-03-03 | Schering Ag | Neue Leukotrien-B¶4¶-Antagonisten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US5410054A (en) * | 1993-07-20 | 1995-04-25 | Merck Frosst Canada, Inc. | Heteroaryl quinolines as inhibitors of leukotriene biosynthesis |
| US20150320705A1 (en) * | 2014-05-08 | 2015-11-12 | Medicinova, Inc. | Method of inhibiting or treating amyotrophic lateral sclerosis with phenoxyalkylcarboxylic acids |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1199871A (en) * | 1967-05-11 | 1970-07-22 | Consolidation Coal Co | Improvements in or relating to Sulfur-Containing Bisphenols |
| JPS508095B1 (enEXAMPLES) * | 1970-01-22 | 1975-04-02 | ||
| BE788749A (fr) * | 1971-09-13 | 1973-03-13 | Takeda Chemical Industries Ltd | Acide 3-(benzoyl trisubstitue)-propionique et son procede de preparation |
| GB2058785B (en) * | 1979-09-05 | 1983-05-25 | Glaxo Group Ltd | Phenol derivatives |
| US4410548A (en) * | 1980-07-09 | 1983-10-18 | Reckitt & Colman Products Limited | Propanolamine derivatives |
| DE3169761D1 (en) * | 1981-01-09 | 1985-05-09 | Fisons Plc | Phenoxy- and thiophenoxy compounds, methods for their preparation and pharmaceutical formulations containing them |
| FR2509725A1 (fr) * | 1981-07-15 | 1983-01-21 | Choay Sa | (hydroxyalkyl)phenylsulfures, leurs procedes de preparation et compositions pharmaceutiques les contenant |
-
1983
- 1983-09-12 NZ NZ205559A patent/NZ205559A/en unknown
- 1983-09-12 IL IL69691A patent/IL69691A/xx unknown
- 1983-09-16 AU AU19190/83A patent/AU557953B2/en not_active Ceased
- 1983-09-19 KR KR1019830004395A patent/KR840006336A/ko not_active Withdrawn
- 1983-09-21 CA CA000437216A patent/CA1210770A/en not_active Expired
- 1983-09-21 DE DE8383305588T patent/DE3363942D1/de not_active Expired
- 1983-09-21 IE IE2210/83A patent/IE55971B1/xx unknown
- 1983-09-21 AT AT83305588T patent/ATE20233T1/de not_active IP Right Cessation
- 1983-09-21 PT PT77367A patent/PT77367B/pt unknown
- 1983-09-21 GR GR72486A patent/GR79677B/el unknown
- 1983-09-21 EP EP83305588A patent/EP0104885B1/en not_active Expired
- 1983-09-22 DK DK432783A patent/DK432783A/da not_active Application Discontinuation
- 1983-09-22 ZA ZA837048A patent/ZA837048B/xx unknown
- 1983-09-22 ES ES525824A patent/ES525824A0/es active Granted
- 1983-09-24 JP JP58175237A patent/JPS59139342A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ATE20233T1 (de) | 1986-06-15 |
| DE3363942D1 (en) | 1986-07-10 |
| ES8503323A1 (es) | 1985-02-16 |
| GR79677B (enEXAMPLES) | 1984-10-31 |
| AU1919083A (en) | 1984-03-29 |
| ZA837048B (en) | 1985-05-29 |
| KR840006336A (ko) | 1984-11-29 |
| EP0104885B1 (en) | 1986-06-04 |
| PT77367B (en) | 1986-04-21 |
| EP0104885A1 (en) | 1984-04-04 |
| IE55971B1 (en) | 1991-03-13 |
| IE832210L (en) | 1984-03-23 |
| IL69691A (en) | 1988-01-31 |
| PT77367A (en) | 1983-10-01 |
| AU557953B2 (en) | 1987-01-15 |
| NZ205559A (en) | 1987-08-31 |
| DK432783A (da) | 1984-05-04 |
| CA1210770A (en) | 1986-09-02 |
| ES525824A0 (es) | 1985-02-16 |
| DK432783D0 (da) | 1983-09-22 |
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