CA1042003A - Analogues of prostanoic acids not occurring in nature and process for preparing them - Google Patents
Analogues of prostanoic acids not occurring in nature and process for preparing themInfo
- Publication number
- CA1042003A CA1042003A CA220,062A CA220062A CA1042003A CA 1042003 A CA1042003 A CA 1042003A CA 220062 A CA220062 A CA 220062A CA 1042003 A CA1042003 A CA 1042003A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- dimethyl
- trans
- compound
- acid
- 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.)
- Expired
Links
- 239000002253 acid Substances 0.000 title claims abstract description 41
- 150000007513 acids Chemical class 0.000 title abstract description 15
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- 238000000034 method Methods 0.000 claims abstract description 41
- 230000008569 process Effects 0.000 claims abstract description 29
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 89
- -1 benzyloxybutylmagnesiumchloride Chemical compound 0.000 claims description 59
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 150000001299 aldehydes Chemical class 0.000 claims description 25
- 150000002148 esters Chemical class 0.000 claims description 24
- 150000002576 ketones Chemical class 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 21
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 17
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 15
- 229910052987 metal hydride Inorganic materials 0.000 claims description 15
- 150000004681 metal hydrides Chemical class 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 150000001298 alcohols Chemical class 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 238000005907 ketalization reaction Methods 0.000 claims description 10
- 150000003555 thioacetals Chemical class 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 8
- 230000001476 alcoholic effect Effects 0.000 claims description 8
- 238000005882 aldol condensation reaction Methods 0.000 claims description 8
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 239000012312 sodium hydride Substances 0.000 claims description 8
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 8
- 239000003377 acid catalyst Substances 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 7
- 150000007530 organic bases Chemical class 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- GTBRTGPZZALPNS-MXHVRSFHSA-N cyanoketone Chemical compound C1C=C2C(C)(C)C(=O)[C@H](C#N)C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GTBRTGPZZALPNS-MXHVRSFHSA-N 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 5
- 238000007171 acid catalysis Methods 0.000 claims description 5
- 238000006555 catalytic reaction Methods 0.000 claims description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
- 235000006408 oxalic acid Nutrition 0.000 claims description 5
- 239000003880 polar aprotic solvent Substances 0.000 claims description 5
- BXNCQMCBHOWUPG-UHFFFAOYSA-N 3-oxo-2-(3-phenylmethoxypropyl)cyclopentane-1-carbonitrile Chemical compound O=C1CCC(C#N)C1CCCOCC1=CC=CC=C1 BXNCQMCBHOWUPG-UHFFFAOYSA-N 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- 150000001241 acetals Chemical class 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- JMJBNBBYRRYQBA-UHFFFAOYSA-N ethyl 3-oxo-2-(3-phenylmethoxypropyl)cyclopentane-1-carboxylate Chemical compound CCOC(=O)C1CCC(=O)C1CCCOCC1=CC=CC=C1 JMJBNBBYRRYQBA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- SZYDQZUBESKSFS-UHFFFAOYSA-N ethyl 3-oxo-2-(3-oxopropyl)cyclopentane-1-carboxylate Chemical compound CCOC(=O)C1CCC(=O)C1CCC=O SZYDQZUBESKSFS-UHFFFAOYSA-N 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 229910052717 sulfur Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims description 2
- 150000004662 dithiols Chemical class 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical class O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- MFTLOLJZTDYBGF-UHFFFAOYSA-N 1-(1,3-dithiolan-2-yl)-7-phenylmethoxyheptan-3-one Chemical compound S1CCSC1CCC(=O)CCCCOCC1=CC=CC=C1 MFTLOLJZTDYBGF-UHFFFAOYSA-N 0.000 claims 3
- IMJHXYPAOYSKMY-UHFFFAOYSA-N 2-ethyl-6-phenylmethoxyhexanal Chemical compound CCC(C=O)CCCCOCC1=CC=CC=C1 IMJHXYPAOYSKMY-UHFFFAOYSA-N 0.000 claims 3
- ZQOUBIWQOZJJRO-UHFFFAOYSA-N 3-(1,3-dithiolan-2-yl)propanenitrile Chemical compound N#CCCC1SCCS1 ZQOUBIWQOZJJRO-UHFFFAOYSA-N 0.000 claims 3
- MHSRNIMPFDRKFI-NPKGFUJDSA-N (z)-7-[2-[(e)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]hept-4-enoic acid Chemical compound CCCCCC(O)\C=C\C1CCC(=O)C1CC\C=C/CCC(O)=O MHSRNIMPFDRKFI-NPKGFUJDSA-N 0.000 claims 2
- WMFJBWYZMHBLER-VGGPMKHUSA-N CCCCCCCC(O)\C=C\C1CCC(=O)C1CC\C=C/CCC(O)=O Chemical compound CCCCCCCC(O)\C=C\C1CCC(=O)C1CC\C=C/CCC(O)=O WMFJBWYZMHBLER-VGGPMKHUSA-N 0.000 claims 2
- CYLMOWYIVWTQKY-MCFSWSPNSA-N OC(/C=C/C1C(C(CC1)=O)CCC=C/CCC(=O)O)C(COCC)(C)C Chemical compound OC(/C=C/C1C(C(CC1)=O)CCC=C/CCC(=O)O)C(COCC)(C)C CYLMOWYIVWTQKY-MCFSWSPNSA-N 0.000 claims 2
- QZSJFPXEVMMYQP-UHFFFAOYSA-N ethyl 4-[2-(1,3-dithiolan-2-yl)ethyl]-8,8-dimethyl-6,10-dioxaspiro[4.5]decane-3-carboxylate Chemical compound S1CCSC1CCC1C(C(=O)OCC)CCC21OCC(C)(C)CO2 QZSJFPXEVMMYQP-UHFFFAOYSA-N 0.000 claims 2
- PSOLOGTXFROOBF-UHFFFAOYSA-N (9-methyl-2-oxodecyl)phosphonic acid Chemical compound CC(C)CCCCCCC(=O)CP(O)(O)=O PSOLOGTXFROOBF-UHFFFAOYSA-N 0.000 claims 1
- KEVVGZZBMYUOJI-ZHACJKMWSA-N (e)-1-[4-(1,3-dithiolan-2-yl)-8,8-dimethyl-6,10-dioxaspiro[4.5]decan-3-yl]dec-1-en-3-one Chemical compound S1CCSC1C1C(/C=C/C(=O)CCCCCCC)CCC21OCC(C)(C)CO2 KEVVGZZBMYUOJI-ZHACJKMWSA-N 0.000 claims 1
- CNUBPHPWSGDATL-ZHACJKMWSA-N (e)-1-[4-[2-(1,3-dithiolan-2-yl)ethyl]-8,8-dimethyl-6,10-dioxaspiro[4.5]decan-3-yl]dec-1-en-3-ol Chemical compound S1CCSC1CCC1C(/C=C/C(O)CCCCCCC)CCC21OCC(C)(C)CO2 CNUBPHPWSGDATL-ZHACJKMWSA-N 0.000 claims 1
- CVYXRRHMEXOUHY-CMDGGOBGSA-N (e)-1-[4-[2-(1,3-dithiolan-2-yl)ethyl]-8,8-dimethyl-6,10-dioxaspiro[4.5]decan-3-yl]oct-1-en-3-ol Chemical compound S1CCSC1CCC1C(/C=C/C(O)CCCCC)CCC21OCC(C)(C)CO2 CVYXRRHMEXOUHY-CMDGGOBGSA-N 0.000 claims 1
- RYYBUINQIPCLLH-CMDGGOBGSA-N (e)-1-[4-[2-(1,3-dithiolan-2-yl)ethyl]-8,8-dimethyl-6,10-dioxaspiro[4.5]decan-3-yl]oct-1-en-3-one Chemical compound S1CCSC1CCC1C(/C=C/C(=O)CCCCC)CCC21OCC(C)(C)CO2 RYYBUINQIPCLLH-CMDGGOBGSA-N 0.000 claims 1
- LQZCYXCHWNQBKX-UHFFFAOYSA-N 1-dimethoxyphosphorylheptan-2-one Chemical compound CCCCCC(=O)CP(=O)(OC)OC LQZCYXCHWNQBKX-UHFFFAOYSA-N 0.000 claims 1
- JRKBHRUFKOFOTO-FOCLMDBBSA-N 3-[8,8-dimethyl-3-[(e)-3-(oxan-2-yloxy)dec-1-enyl]-6,10-dioxaspiro[4.5]decan-4-yl]propanal Chemical compound C1CC2(OCC(C)(C)CO2)C(CCC=O)C1/C=C/C(CCCCCCC)OC1CCCCO1 JRKBHRUFKOFOTO-FOCLMDBBSA-N 0.000 claims 1
- IKDVEOVENBQIPX-BUHFOSPRSA-N 3-[8,8-dimethyl-3-[(e)-3-(oxan-2-yloxy)oct-1-enyl]-6,10-dioxaspiro[4.5]decan-4-yl]propanal Chemical compound C1CC2(OCC(C)(C)CO2)C(CCC=O)C1/C=C/C(CCCCC)OC1CCCCO1 IKDVEOVENBQIPX-BUHFOSPRSA-N 0.000 claims 1
- KNLAYBVEYMJALP-VAWYXSNFSA-N 4-(1,3-dithiolan-2-yl)-8,8-dimethyl-3-[(E)-3-(oxan-2-yloxy)oct-1-enyl]-6,10-dioxaspiro[4.5]decane Chemical compound O1C(CCCC1)OC(/C=C/C1C(C2(OCC(CO2)(C)C)CC1)C1SCCS1)CCCCC KNLAYBVEYMJALP-VAWYXSNFSA-N 0.000 claims 1
- KECFFCWJNUASPK-BUHFOSPRSA-N 4-[2-(1,3-dithiolan-2-yl)ethyl]-8,8-dimethyl-3-[(E)-3-(oxan-2-yloxy)dec-1-enyl]-6,10-dioxaspiro[4.5]decane Chemical compound O1C(CCCC1)OC(/C=C/C1C(C2(OCC(CO2)(C)C)CC1)CCC1SCCS1)CCCCCCC KECFFCWJNUASPK-BUHFOSPRSA-N 0.000 claims 1
- VDEZCJCGFWJNTI-UHFFFAOYSA-N CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)C(COCC)(C)C)CCC=C/CCC(=O)O)C Chemical compound CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)C(COCC)(C)C)CCC=C/CCC(=O)O)C VDEZCJCGFWJNTI-UHFFFAOYSA-N 0.000 claims 1
- TUAVCOMYSGLKGT-UHFFFAOYSA-N CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)CCCCC)CCC=C/CCC(=O)O)C Chemical compound CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)CCCCC)CCC=C/CCC(=O)O)C TUAVCOMYSGLKGT-UHFFFAOYSA-N 0.000 claims 1
- SIYPVQQESRZULE-UHFFFAOYSA-N CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)CCCCCCC)CCC=C/CCC(=O)O)C Chemical compound CC1(COC2(OC1)C(C(CC2)C=CC(OC2OCCCC2)CCCCCCC)CCC=C/CCC(=O)O)C SIYPVQQESRZULE-UHFFFAOYSA-N 0.000 claims 1
- 150000003180 prostaglandins Chemical class 0.000 abstract description 7
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 6
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 235000013350 formula milk Nutrition 0.000 description 131
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 235000019441 ethanol Nutrition 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical class CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229960004132 diethyl ether Drugs 0.000 description 10
- 238000004821 distillation Methods 0.000 description 10
- 229940076134 benzene Drugs 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000009471 action Effects 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000001131 transforming effect Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- VRAARYWXGUUQRR-UHFFFAOYSA-N 4-chlorobutoxymethylbenzene Chemical compound ClCCCCOCC1=CC=CC=C1 VRAARYWXGUUQRR-UHFFFAOYSA-N 0.000 description 3
- KFXPOIKSDYRVKS-ARJAWSKDSA-N 4Z-heptenoic acid Chemical compound CC\C=C/CCC(O)=O KFXPOIKSDYRVKS-ARJAWSKDSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 230000003182 bronchodilatating effect Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- OSDZHDOKXGSWOD-UHFFFAOYSA-N nitroxyl;hydrochloride Chemical compound Cl.O=N OSDZHDOKXGSWOD-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
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- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- ANBAVAXLDVVQER-UHFFFAOYSA-N C(C1=CC=CC=C1)OCCCC[Li] Chemical compound C(C1=CC=CC=C1)OCCCC[Li] ANBAVAXLDVVQER-UHFFFAOYSA-N 0.000 description 1
- QPGAPWSKJCBGKB-UHFFFAOYSA-N CC(C)CC(=O)C(C)(C)P(O)(O)=O Chemical compound CC(C)CC(=O)C(C)(C)P(O)(O)=O QPGAPWSKJCBGKB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 101100273284 Homo sapiens CASP4 gene Proteins 0.000 description 1
- 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 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 101150001411 STX2 gene Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 230000003509 anti-fertility effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
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- 230000036772 blood pressure Effects 0.000 description 1
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- 244000309464 bull Species 0.000 description 1
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- 239000007795 chemical reaction product Substances 0.000 description 1
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- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexyl-acetic acid Natural products OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- IHNFNNQTKXCDSV-UHFFFAOYSA-N dimethyl 2-oxononyl phosphate Chemical compound CCCCCCCC(=O)COP(=O)(OC)OC IHNFNNQTKXCDSV-UHFFFAOYSA-N 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229940117969 neopentyl glycol Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000004810 partition chromatography Methods 0.000 description 1
- 229940059574 pentaerithrityl Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical compound OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 description 1
- 239000003799 water insoluble solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/06—Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
-
- 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
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- 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
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
-
- 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
- C07C45/65—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 splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
- C07C45/66—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 splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2407186A DE2407186C2 (de) | 1974-02-15 | 1974-02-15 | Neue, natürlich nicht vorkommende Analoga von Prostansäuren und Verfahren zu ihrer Herstellung, sowie diese Analoga von Prostansäuren enthaltende Arzneimittel |
DE19742445526 DE2445526A1 (de) | 1974-09-24 | 1974-09-24 | Bronchodilatorisch wirksame arzneimittel |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1042003A true CA1042003A (en) | 1978-11-07 |
Family
ID=25766631
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA220,062A Expired CA1042003A (en) | 1974-02-15 | 1975-02-13 | Analogues of prostanoic acids not occurring in nature and process for preparing them |
Country Status (13)
Country | Link |
---|---|
JP (1) | JPS5854139B2 (zh) |
CA (1) | CA1042003A (zh) |
CH (1) | CH617675A5 (zh) |
DK (1) | DK55575A (zh) |
ES (2) | ES434590A1 (zh) |
FR (1) | FR2261004B1 (zh) |
GB (1) | GB1507501A (zh) |
HU (1) | HU174323B (zh) |
IE (1) | IE41407B1 (zh) |
IL (1) | IL46615A0 (zh) |
LU (1) | LU71837A1 (zh) |
NL (1) | NL7501560A (zh) |
SE (1) | SE7501653L (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4387241A (en) * | 1974-11-01 | 1983-06-07 | American Cyanamid Company | Novel 16-aryloxy-17,18,19,20-tetranorprostanoic acids and derivatives |
US4032561A (en) * | 1975-05-27 | 1977-06-28 | The Upjohn Company | 17-Phenyl-18,19,20-trinor-cis-4,5-didehydro-PGF1.sub.α compounds |
ZA771725B (en) * | 1976-04-21 | 1978-02-22 | Upjohn Co | Ayal prostaglandin analogs |
US4228296A (en) * | 1979-01-24 | 1980-10-14 | American Cyanamid Company | Novel 16-aryloxy-17,18,19,20-tetranorprostanoic acids and derivatives |
-
1975
- 1975-02-10 NL NL7501560A patent/NL7501560A/xx not_active Application Discontinuation
- 1975-02-10 ES ES434590A patent/ES434590A1/es not_active Expired
- 1975-02-11 IL IL46615A patent/IL46615A0/xx unknown
- 1975-02-12 HU HU75HO1768A patent/HU174323B/hu unknown
- 1975-02-13 LU LU71837A patent/LU71837A1/xx unknown
- 1975-02-13 CA CA220,062A patent/CA1042003A/en not_active Expired
- 1975-02-14 CH CH183475A patent/CH617675A5/de not_active IP Right Cessation
- 1975-02-14 IE IE293/75A patent/IE41407B1/en unknown
- 1975-02-14 DK DK55575*#A patent/DK55575A/da not_active Application Discontinuation
- 1975-02-14 SE SE7501653A patent/SE7501653L/xx unknown
- 1975-02-15 JP JP50019371A patent/JPS5854139B2/ja not_active Expired
- 1975-02-17 GB GB6535/75A patent/GB1507501A/en not_active Expired
- 1975-02-17 FR FR7504857A patent/FR2261004B1/fr not_active Expired
-
1976
- 1976-10-30 ES ES452901A patent/ES452901A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
JPS50123644A (zh) | 1975-09-29 |
IE41407L (en) | 1975-08-15 |
JPS5854139B2 (ja) | 1983-12-02 |
FR2261004B1 (zh) | 1978-07-21 |
DK55575A (zh) | 1975-10-13 |
LU71837A1 (zh) | 1977-01-05 |
FR2261004A1 (zh) | 1975-09-12 |
SE7501653L (zh) | 1975-08-18 |
AU7817775A (en) | 1976-08-19 |
GB1507501A (en) | 1978-04-19 |
ES434590A1 (es) | 1977-04-01 |
CH617675A5 (en) | 1980-06-13 |
IL46615A0 (en) | 1975-04-25 |
ES452901A1 (es) | 1977-11-01 |
NL7501560A (nl) | 1975-08-19 |
HU174323B (hu) | 1979-12-28 |
IE41407B1 (en) | 1980-01-02 |
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