CS232719B2 - Method of 6-alpha-carbaprostaglandine derivatives production - Google Patents

Method of 6-alpha-carbaprostaglandine derivatives production Download PDF

Info

Publication number: CS232719B2
Authority: CS; Czechoslovakia
Prior art keywords: acid; group; free; yloxy; alkyl
Prior art date: 1980-12-19

Application number

CS819138A

Other languages

Czech (cs)

English (en)

Other versions

CS913881A2 (en

Inventor

Werner SKUBALA

Bernd Raduechel

Norbert Schwarz

Helmut Vorbrueggen

Jorge Casals-Stenzel

Ekkerhard Schillinger

Michael H Town

Original Assignee

Schering Ag

Priority date (The priority date 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 date listed.)

1980-12-19

Filing date

1981-12-09

Publication date

1985-02-14

1981-12-09 Application filed by Schering Ag filed Critical Schering Ag

1984-06-18 Publication of CS913881A2 publication Critical patent/CS913881A2/cs

1985-02-14 Publication of CS232719B2 publication Critical patent/CS232719B2/cs

Links

238000000034 method Methods 0.000 title claims description 20
238000004519 manufacturing process Methods 0.000 title description 2
-1 hydroxymethylene Chemical class 0.000 claims abstract description 79
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 30
239000002253 acid Substances 0.000 claims abstract description 23
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims abstract description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 58
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
239000002585 base Substances 0.000 claims description 9
230000008569 process Effects 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 3
229910052783 alkali metal Inorganic materials 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 abstract description 6
229920006395 saturated elastomer Polymers 0.000 abstract description 6
125000003118 aryl group Chemical group 0.000 abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
125000001931 aliphatic group Chemical group 0.000 abstract description 3
125000003107 substituted aryl group Chemical group 0.000 abstract description 3
230000000144 pharmacologic effect Effects 0.000 abstract description 2
150000002431 hydrogen Chemical group 0.000 abstract 2
XZFRIPGNUQRGPI-WLPVIMDJSA-N Carbacyclin Chemical class C1\C(=C\CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 XZFRIPGNUQRGPI-WLPVIMDJSA-N 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
239000000243 solution Substances 0.000 description 41
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
239000012230 colorless oil Substances 0.000 description 27
238000001228 spectrum Methods 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
150000002576 ketones Chemical class 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
238000002329 infrared spectrum Methods 0.000 description 12
230000007935 neutral effect Effects 0.000 description 11
239000003921 oil Substances 0.000 description 11
239000007858 starting material Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
235000011054 acetic acid Nutrition 0.000 description 10
239000002904 solvent Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000000725 suspension Substances 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
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
230000007017 scission Effects 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
230000009471 action Effects 0.000 description 6
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
239000000284 extract Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000012279 sodium borohydride Substances 0.000 description 6
229910000033 sodium borohydride Inorganic materials 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
239000011737 fluorine Substances 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
150000003180 prostaglandins Chemical class 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
ZOUYMLXOFDNVRK-UHFFFAOYSA-N 3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-one Chemical compound C1CCC2CC(=O)CC21 ZOUYMLXOFDNVRK-UHFFFAOYSA-N 0.000 description 4
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
239000005909 Kieselgur Substances 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
238000013375 chromatographic separation Methods 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
229940094443 oxytocics prostaglandins Drugs 0.000 description 4
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 4
XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 4
239000000047 product Substances 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000000126 substance Substances 0.000 description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
AEBWATHAIVJLTA-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalene Chemical compound C1CCC2CCCC21 AEBWATHAIVJLTA-UHFFFAOYSA-N 0.000 description 3
SZNNKIKETRJKQX-UHFFFAOYSA-N 2-chloroacetic acid;lithium Chemical compound [Li].OC(=O)CCl SZNNKIKETRJKQX-UHFFFAOYSA-N 0.000 description 3
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
QDZARNQKIZUXDK-UHFFFAOYSA-N [C-][N+]#N Chemical compound [C-][N+]#N QDZARNQKIZUXDK-UHFFFAOYSA-N 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
229960002986 dinoprostone Drugs 0.000 description 3
238000004821 distillation Methods 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
238000006266 etherification reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
150000004679 hydroxides Chemical class 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
150000003815 prostacyclins Chemical class 0.000 description 3
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000007127 saponification reaction Methods 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
GGMCUAHRMNAHMY-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3,3-dimethyloct-5-yn-2-one Chemical compound CCC#CCC(C)(C)C(=O)CP(=O)(OC)OC GGMCUAHRMNAHMY-UHFFFAOYSA-N 0.000 description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
101100310593 Candida albicans (strain SC5314 / ATCC MYA-2876) SOD4 gene Proteins 0.000 description 2
YVHAIVPPUIZFBA-UHFFFAOYSA-N Cyclopentylacetic acid Chemical compound OC(=O)CC1CCCC1 YVHAIVPPUIZFBA-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
MYHXHCUNDDAEOZ-UHFFFAOYSA-N Prostaglandin A&2% Natural products CCCCCC(O)C=CC1C=CC(=O)C1CC=CCCCC(O)=O MYHXHCUNDDAEOZ-UHFFFAOYSA-N 0.000 description 2
101100190148 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PGA2 gene Proteins 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910001854 alkali hydroxide Inorganic materials 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000004531 blood pressure lowering effect Effects 0.000 description 2
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
239000000920 calcium hydroxide Substances 0.000 description 2
229910001861 calcium hydroxide Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 2
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
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IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000004321 preservation Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
HNDXKIMMSFCCFW-UHFFFAOYSA-N propane-2-sulphonic acid Chemical compound CC(C)S(O)(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
235000013580 sausages Nutrition 0.000 description 1
230000035939 shock Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000002689 soil Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000008359 toxicosis Effects 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000002618 waking effect Effects 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- 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
- C07D317/72—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 spiro-condensed with carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C405/005—Analogues or derivatives having the five membered ring replaced by other rings
- C07C405/0075—Analogues or derivatives having the five membered ring replaced by other rings having the side-chains or their analogues or derivatives attached to a condensed ring system
- C07C405/0083—Analogues or derivatives having the five membered ring replaced by other rings having the side-chains or their analogues or derivatives attached to a condensed ring system which is only ortho or peri condensed, e.g. carbacyclins
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4015—Esters of acyclic unsaturated acids

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Cardiology (AREA)
Molecular Biology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Pulmonology (AREA)
Diabetes (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Pyrane Compounds (AREA)
Tires In General (AREA)
Polyesters Or Polycarbonates (AREA)

CS819138A 1980-12-19 1981-12-09 Method of 6-alpha-carbaprostaglandine derivatives production CS232719B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19803048906 DE3048906A1 (de)	1980-12-19	1980-12-19	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel

Publications (2)

Publication Number	Publication Date
CS913881A2 CS913881A2 (en)	1984-06-18
CS232719B2 true CS232719B2 (en)	1985-02-14

Family

ID=6120200

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS819138A CS232719B2 (en)	1980-12-19	1981-12-09	Method of 6-alpha-carbaprostaglandine derivatives production

Country Status (21)

Country	Link
US (2)	US4423067A (fr)
EP (1)	EP0055208B1 (fr)
JP (1)	JPS57145833A (fr)
AT (1)	ATE12094T1 (fr)
AU (1)	AU548662B2 (fr)
CA (1)	CA1223255A (fr)
CS (1)	CS232719B2 (fr)
DE (2)	DE3048906A1 (fr)
DK (1)	DK169815B1 (fr)
ES (1)	ES508124A0 (fr)
FI (1)	FI71122C (fr)
GR (1)	GR77633B (fr)
HU (1)	HU187398B (fr)
IE (1)	IE52432B1 (fr)
IL (1)	IL64577A0 (fr)
NO (1)	NO155537C (fr)
NZ (1)	NZ199319A (fr)
PH (1)	PH19419A (fr)
SU (1)	SU1367856A3 (fr)
YU (1)	YU293081A (fr)
ZA (1)	ZA818788B (fr)

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DE3048906A1 (de) *	1980-12-19	1982-07-15	Schering Ag, 1000 Berlin Und 4619 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE3306125A1 (de) *	1983-02-18	1984-08-23	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
JPS58188850A (ja) *	1982-04-26	1983-11-04	Sumitomo Chem Co Ltd	新規ビシクロオクタン誘導体およびその製造法
DE3225288A1 (de) *	1982-07-02	1984-01-19	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE3225287A1 (de) *	1982-07-02	1984-01-05	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacyclinamide, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE3226550A1 (de) *	1982-07-13	1984-01-19	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
JPS59141536A (ja) *	1983-02-01	1984-08-14	Sumitomo Chem Co Ltd	新規ビシクロオクタン誘導体
DE3306123A1 (de) *	1983-02-18	1984-09-06	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
CA1252780A (fr) *	1983-07-26	1989-04-18	Kazuo Koyama	Derives de carbacycline, procede de preparation et composes les contenant
JPS60172941A (ja) *	1984-02-16	1985-09-06	Sankyo Co Ltd	カルバサイクリン類
JPS60181041A (ja) *	1984-02-29	1985-09-14	Sankyo Co Ltd	カルバサイクリン誘導体
US4971987A (en) *	1984-07-27	1990-11-20	Schering Aktiengesellschaft	New carbacycline, process for their production and their use as a drug
DE3428266A1 (de) *	1984-07-27	1986-01-30	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
JPH0680027B2 (ja) *	1985-09-18	1994-10-12	財団法人相模中央化学研究所	プロスタサイクリン類及びこれらを含有する薬剤
CA1322197C (fr)	1987-07-17	1993-09-14	Bernd Buchmann	Derives 9-halogene-(z)-prostaglandine, procede pour leur production et leur utilisation comme agents pharmaceutiques
US5891910A (en) *	1987-07-17	1999-04-06	Schering Aktiengesellschaft	9-halogen-(Z) prostaglandin derivatives, process for their production and their use as pharmaceutical agents
DE3835162A1 (de) *	1988-10-13	1990-04-19	Schering Ag	(1s,2s,3r,5r)-2-((3s)-2-halogen-3-hydroxy-1-alken(inyl))-3-trialkylsilyloxy-7,7-(2,2-dimethyl-trimethylendioxy)-bicyclo-(3.3.0)-octan-verbindungen und verfahren zu deren herstellung
DE19828881A1 (de) *	1998-06-22	1999-12-23	Schering Ag	Oxidationsinhibitor bei Prostan-Derivaten
KR20020016938A (ko)	1999-08-05	2002-03-06	야스이 쇼사꾸	함질소화합물을 유효성분으로 하는 신경장해개선제
US20090035260A1 (en) *	2002-07-29	2009-02-05	Therapicon Srl	Enhanced nasal composition of active peptide
US20090124697A1 (en) *	2003-12-16	2009-05-14	United Therapeutics Corporation	Inhalation formulations of treprostinil
KR101161889B1 (ko) *	2003-12-16	2012-07-02	유나이티드 쎄러퓨틱스 코포레이션	허혈성 병변의 치료 및 예방을 위한 트레프로스티닐의 용도
ITMI20040235A1 (it) *	2004-02-13	2004-05-13	Therapicon Srl	Preparazione farmaceutica per il cavo orale
CN101090714A (zh) *	2004-07-26	2007-12-19	康泽里克斯公司	通过吸入伊洛前列素和微粒制剂治疗肺动脉高血压症
CA2654492C (fr)	2006-05-15	2017-06-27	United Therapeutics Corporation	Administration de treprostinil utilisant un inhalateur a dose mesuree
DE102006026786A1 (de)	2006-06-07	2007-12-13	Joachim Kern	Dosierinhalator
EP2094273B1 (fr)	2006-11-16	2013-03-06	Gemmus Pharma Inc.	Agonistes EP2 et EP4 en tant qu'agents destinés au traitement d'une infection virale de l'influenza A
WO2011047048A1 (fr)	2009-10-14	2011-04-21	Gemmus Pharma, Inc.	Traitement par polythérapie pour infections virales
IL280864B2 (en)	2013-08-09	2024-03-01	Ardelyx Inc	Compounds and methods for inhibiting phosphate transport
US10799653B2 (en)	2017-01-09	2020-10-13	United Therapeutics Corporation	Aerosol delivery device and method for manufacturing and operating the same
EP3972599A1 (fr)	2019-05-21	2022-03-30	Ardelyx, Inc.	Combinaison pour baisser le phosphate sérique chez un patient
JP2023523557A (ja)	2020-04-17	2023-06-06	ユナイテッドセラピューティクスコーポレイション	間質性肺疾患の治療における使用のためのトレプロスチニル

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US4036075A (en) *	1976-05-05	1977-07-19	Outboard Marine Corporation	Variable speed power transmission including means for minimizing backlash
JPS5495552A (en) *	1978-01-06	1979-07-28	Sankyo Co Ltd	Prostacyline derivative and its preparation
GB2038333B (en) *	1978-01-26	1982-10-06	Erba Farmitalia	12 -formyl- (20 12)octanor-9-deoxy-9 -methylene pgi derivatives
US4705806A (en) *	1978-02-13	1987-11-10	Morton Jr Douglas R	Prostacyclin analogs
US4238414A (en) *	1978-02-13	1980-12-09	The Upjohn Company	2-Decarboxy-2-aminomethyl-6a-carba-PGI2 compounds
JPS54119441A (en) *	1978-03-09	1979-09-17	Sumitomo Chem Co Ltd	Novel bicyclooctane derivative
GB2017699B (en) *	1978-03-31	1983-01-12	Ono Pharmaceutical Co	6,9-methano-pgi2 analogues
DE2845770A1 (de) *	1978-10-19	1980-04-30	Schering Ag	Neue prostacyclin-derivate und verfahren zu ihrer herstellung
CA1201712A (fr) *	1980-02-28	1986-03-11	Paul A. Aristoff	Analogues de la carbacycline
US4338457A (en) *	1980-02-28	1982-07-06	The Upjohn Company	Composition and process
US4346041A (en) *	1980-02-28	1982-08-24	The Upjohn Company	Composition and process
EP0036730B1 (fr) *	1980-03-21	1985-01-02	Sumitomo Chemical Company, Limited	Dérivés bicyclooctane, procédés pour leur préparation, compositions pharmaceutiques les contenant, leur utilisation comme produits pharmaceutiques et précurseurs
US4420632A (en) *	1980-04-15	1983-12-13	The Upjohn Company	Composition and process
US4306076A (en) *	1980-04-23	1981-12-15	The Upjohn Company	Inter-phenylene CBA compounds
DE3048906A1 (de) *	1980-12-19	1982-07-15	Schering Ag, 1000 Berlin Und 4619 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
US4349689A (en) *	1980-12-22	1982-09-14	The Upjohn Company	Methano carbacyclin analogs
DE3121155A1 (de) *	1981-05-22	1982-12-09	Schering Ag, 1000 Berlin Und 4619 Bergkamen	Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel

1980
- 1980-12-19 DE DE19803048906 patent/DE3048906A1/de not_active Withdrawn
1981
- 1981-12-09 CS CS819138A patent/CS232719B2/cs unknown
- 1981-12-10 SU SU813363101A patent/SU1367856A3/ru active
- 1981-12-10 FI FI813967A patent/FI71122C/fi not_active IP Right Cessation
- 1981-12-14 YU YU02930/81A patent/YU293081A/xx unknown
- 1981-12-17 DE DE8181730124T patent/DE3169305D1/de not_active Expired
- 1981-12-17 EP EP81730124A patent/EP0055208B1/fr not_active Expired
- 1981-12-17 AT AT81730124T patent/ATE12094T1/de not_active IP Right Cessation
- 1981-12-17 GR GR66826A patent/GR77633B/el unknown
- 1981-12-18 PH PH26655A patent/PH19419A/en unknown
- 1981-12-18 JP JP56203814A patent/JPS57145833A/ja active Granted
- 1981-12-18 AU AU78676/81A patent/AU548662B2/en not_active Ceased
- 1981-12-18 ZA ZA818788A patent/ZA818788B/xx unknown
- 1981-12-18 IE IE2997/81A patent/IE52432B1/en not_active IP Right Cessation
- 1981-12-18 IL IL64577A patent/IL64577A0/xx not_active IP Right Cessation
- 1981-12-18 DK DK564181A patent/DK169815B1/da not_active IP Right Cessation
- 1981-12-18 NO NO814357A patent/NO155537C/no unknown
- 1981-12-18 HU HU813874A patent/HU187398B/hu not_active IP Right Cessation
- 1981-12-18 CA CA000392646A patent/CA1223255A/fr not_active Expired
- 1981-12-18 ES ES508124A patent/ES508124A0/es active Granted
- 1981-12-18 NZ NZ199319A patent/NZ199319A/en unknown
- 1981-12-21 US US06/333,099 patent/US4423067A/en not_active Expired - Lifetime
1985
- 1985-05-28 US US06/738,545 patent/US4708963A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
NO155537B (no)	1987-01-05
FI71122C (fi)	1986-11-24
ATE12094T1 (de)	1985-03-15
FI813967L (fi)	1982-06-20
EP0055208A3 (en)	1982-08-25
AU548662B2 (en)	1986-01-02
IE812997L (en)	1982-06-19
ZA818788B (en)	1982-11-24
DE3048906A1 (de)	1982-07-15
YU293081A (en)	1983-10-31
IL64577A0 (en)	1982-03-31
ES8300090A1 (es)	1982-11-01
US4423067A (en)	1983-12-27
NZ199319A (en)	1985-07-12
EP0055208A2 (fr)	1982-06-30
NO814357L (no)	1982-06-21
JPS6228937B2 (fr)	1987-06-23
DE3169305D1 (en)	1985-04-18
ES508124A0 (es)	1982-11-01
AU7867681A (en)	1982-06-24
DK169815B1 (da)	1995-03-06
CA1223255A (fr)	1987-06-23
IE52432B1 (en)	1987-10-28
CS913881A2 (en)	1984-06-18
NO155537C (no)	1987-04-15
US4708963A (en)	1987-11-24
SU1367856A3 (ru)	1988-01-15
HU187398B (en)	1985-12-28
FI71122B (fi)	1986-08-14
GR77633B (fr)	1984-09-25
JPS57145833A (en)	1982-09-09
PH19419A (en)	1986-04-10
EP0055208B1 (fr)	1985-03-13
DK564181A (da)	1982-06-20

Publication	Publication Date	Title
CS232719B2 (en)	1985-02-14	Method of 6-alpha-carbaprostaglandine derivatives production
US4692464A (en)	1987-09-08	Novel prostacyclin derivatives and a process for the preparation thereof
NO157060B (no)	1987-10-05	Analogifremgangsmte ved fremstilling av terapeutisk aktive carbacycliner.
FI77645B (fi)	1988-12-30	Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara 1a,1b-dihomo-3-oxakarbacyklinderivat.
US4497830A (en)	1985-02-05	Carbacyclins, their preparation and pharmacological use
US4954524A (en)	1990-09-04	Carbacylcins, their preparation and use as medicinal agents
HU191150B (en)	1987-01-28	Process for producing new prostacycline derivatives
JPH0446256B2 (fr)	1992-07-29
US4618626A (en)	1986-10-21	Novel carbacyclin esters, process for the preparation thereof, and their use as medicinal agents
FI78064C (fi)	1989-06-12	Foerfarande foer framstaellning av terapeutiskt anvaendbara karbacyklinderivat.
US4532236A (en)	1985-07-30	Certain prostacyclins and their blood-pressure-lowering and thrombocyte-aggregation-inhibiting compositions and methods
CS256374B2 (en)	1988-04-15	Method of prosthaglandine derivatives production
US4827017A (en)	1989-05-02	Novel carbacyclins, processes for their production and their use as medicinal agents
JPH036145B2 (fr)	1991-01-29
JPH0437817B2 (fr)	1992-06-22
JPH0510330B2 (fr)	1993-02-09
JPH0583557B2 (fr)	1993-11-26