CA1198420A - 9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation - Google Patents

9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation

Info

Publication number: CA1198420A
Authority: CA; Canada
Prior art keywords: hydroxy; alkyl; hydrogen; compound; formula
Prior art date: 1978-01-26
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

Application number

CA000416726A

Other languages

English (en)

Inventor

Carmelo Gandolfi

Carlo Passarotti

William Fava

Angelo Fumagalli

Franco Faustini

Roberto Ceserani

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pfizer Italia SRL

Original Assignee

Farmitalia Carlo Erba SRL

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.)

1978-01-26

Filing date

1982-11-30

Publication date

1985-12-24

1978-01-26 Priority claimed from IT7819616A external-priority patent/IT7819616A0/it

1978-12-21 Priority claimed from IT3107378A external-priority patent/IT1160370B/it

1979-01-26 Priority claimed from CA000320354A external-priority patent/CA1209133A/fr

1982-11-30 Application filed by Farmitalia Carlo Erba SRL filed Critical Farmitalia Carlo Erba SRL

1985-12-24 Application granted granted Critical

1985-12-24 Publication of CA1198420A publication Critical patent/CA1198420A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims description 96
230000008569 process Effects 0.000 title claims description 18
238000002360 preparation method Methods 0.000 title description 18
150000001875 compounds Chemical class 0.000 claims abstract description 207
-1 Cl-C6-alkyl Chemical group 0.000 claims abstract description 72
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 70
239000001257 hydrogen Substances 0.000 claims abstract description 69
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 68
150000002431 hydrogen Chemical class 0.000 claims abstract description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 34
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 26
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract description 21
125000005865 C2-C10alkynyl group Chemical group 0.000 claims abstract description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
229910052736 halogen Inorganic materials 0.000 claims abstract description 19
150000002367 halogens Chemical class 0.000 claims abstract description 19
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 16
229920006395 saturated elastomer Polymers 0.000 claims abstract description 12
150000002596 lactones Chemical class 0.000 claims abstract description 9
229910052705 radium Inorganic materials 0.000 claims abstract description 9
229910052799 carbon Inorganic materials 0.000 claims abstract description 6
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
150000001721 carbon Chemical group 0.000 claims abstract description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 246
239000000203 mixture Substances 0.000 claims description 71
125000006239 protecting group Chemical group 0.000 claims description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
150000002576 ketones Chemical group 0.000 claims description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
239000003153 chemical reaction reagent Substances 0.000 claims description 13
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
239000011737 fluorine Chemical group 0.000 claims description 8
229910052701 rubidium Inorganic materials 0.000 claims description 7
239000000126 substance Substances 0.000 claims description 7
125000002619 bicyclic group Chemical group 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
238000005935 nucleophilic addition reaction Methods 0.000 claims description 6
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
150000002170 ethers Chemical class 0.000 claims description 4
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 3
125000000753 cycloalkyl group Chemical group 0.000 claims 2
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 5
230000002744 anti-aggregatory effect Effects 0.000 abstract description 3
239000003146 anticoagulant agent Substances 0.000 abstract description 3
230000003529 luteolytic effect Effects 0.000 abstract description 3
230000000026 anti-ulcerogenic effect Effects 0.000 abstract description 2
230000000702 anti-platelet effect Effects 0.000 abstract 1
229940124630 bronchodilator Drugs 0.000 abstract 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 184
239000002253 acid Substances 0.000 description 155
239000000243 solution Substances 0.000 description 120
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 104
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 76
229940035423 ethyl ether Drugs 0.000 description 75
238000006243 chemical reaction Methods 0.000 description 71
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
229940076134 benzene Drugs 0.000 description 62
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 52
238000003756 stirring Methods 0.000 description 47
150000004702 methyl esters Chemical class 0.000 description 41
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 40
239000002904 solvent Substances 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
229940073584 methylene chloride Drugs 0.000 description 31
239000000047 product Substances 0.000 description 31
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 29
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 27
239000012074 organic phase Substances 0.000 description 27
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 26
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
229940022682 acetone Drugs 0.000 description 25
230000007935 neutral effect Effects 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
239000000284 extract Substances 0.000 description 24
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 23
239000003480 eluent Substances 0.000 description 22
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 22
239000000377 silicon dioxide Substances 0.000 description 22
238000011282 treatment Methods 0.000 description 22
150000002148 esters Chemical group 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
229940093499 ethyl acetate Drugs 0.000 description 20
229910052681 coesite Inorganic materials 0.000 description 19
229910052906 cristobalite Inorganic materials 0.000 description 19
235000019439 ethyl acetate Nutrition 0.000 description 19
235000012239 silicon dioxide Nutrition 0.000 description 19
229910052682 stishovite Inorganic materials 0.000 description 19
229910052905 tridymite Inorganic materials 0.000 description 19
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 17
238000001704 evaporation Methods 0.000 description 17
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 16
229910000104 sodium hydride Inorganic materials 0.000 description 16
239000005977 Ethylene Substances 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
150000001241 acetals Chemical class 0.000 description 14
150000007513 acids Chemical class 0.000 description 14
150000001299 aldehydes Chemical class 0.000 description 14
230000009467 reduction Effects 0.000 description 14
238000006722 reduction reaction Methods 0.000 description 14
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
230000003647 oxidation Effects 0.000 description 13
238000007254 oxidation reaction Methods 0.000 description 13
230000002829 reductive effect Effects 0.000 description 13
239000011734 sodium Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 12
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 12
239000003513 alkali Substances 0.000 description 12
229960001123 epoprostenol Drugs 0.000 description 12
230000003287 optical effect Effects 0.000 description 12
239000012071 phase Substances 0.000 description 12
239000012279 sodium borohydride Substances 0.000 description 12
229910000033 sodium borohydride Inorganic materials 0.000 description 12
238000010561 standard procedure Methods 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
229960000583 acetic acid Drugs 0.000 description 11
239000008346 aqueous phase Substances 0.000 description 11
238000000605 extraction Methods 0.000 description 11
238000000746 purification Methods 0.000 description 11
150000003254 radicals Chemical class 0.000 description 11
238000010992 reflux Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
239000002585 base Substances 0.000 description 10
238000001816 cooling Methods 0.000 description 10
229910000027 potassium carbonate Inorganic materials 0.000 description 10
235000011121 sodium hydroxide Nutrition 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
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 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
235000006408 oxalic acid Nutrition 0.000 description 9
229910052708 sodium Inorganic materials 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
150000004678 hydrides Chemical class 0.000 description 8
150000002500 ions Chemical class 0.000 description 8
239000010410 layer Substances 0.000 description 8
150000003333 secondary alcohols Chemical class 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
229910000162 sodium phosphate Inorganic materials 0.000 description 8
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
238000009835 boiling Methods 0.000 description 7
229960001760 dimethyl sulfoxide Drugs 0.000 description 7
239000006185 dispersion Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
239000012280 lithium aluminium hydride Substances 0.000 description 7
239000002480 mineral oil Substances 0.000 description 7
235000010446 mineral oil Nutrition 0.000 description 7
235000015320 potassium carbonate Nutrition 0.000 description 7
238000007127 saponification reaction Methods 0.000 description 7
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 6
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 6
229910010084 LiAlH4 Inorganic materials 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
229960002179 ephedrine Drugs 0.000 description 6
238000004460 liquid liquid chromatography Methods 0.000 description 6
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
229910052725 zinc Inorganic materials 0.000 description 6
239000011701 zinc Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
238000010828 elution Methods 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
235000019799 monosodium phosphate Nutrition 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 5
238000000926 separation method Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
150000003509 tertiary alcohols Chemical class 0.000 description 5
150000003555 thioacetals Chemical class 0.000 description 5
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 4
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 4
MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
241000283986 Lepus Species 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
238000005903 acid hydrolysis reaction Methods 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
230000009471 action Effects 0.000 description 4
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 4
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XODWWDLLPURTOQ-UHFFFAOYSA-N ethyl-[ethyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC[Si](C)(C)O[Si](C)(C)CC XODWWDLLPURTOQ-UHFFFAOYSA-N 0.000 description 1
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238000010438 heat treatment Methods 0.000 description 1
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150000004679 hydroxides Chemical class 0.000 description 1
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FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
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239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
229960002523 mercuric chloride Drugs 0.000 description 1
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
238000006140 methanolysis reaction Methods 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
KXMTXZACPVCDMH-UHFFFAOYSA-N methyl 4-[5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate Chemical compound COC(=O)C1=CC(OC)=C2OCOC2=C1C1=C2OCOC2=C(OC)C=C1CO KXMTXZACPVCDMH-UHFFFAOYSA-N 0.000 description 1
CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
MBAHGFJTIVZLFB-UHFFFAOYSA-N methyl pent-2-enoate Chemical compound CCC=CC(=O)OC MBAHGFJTIVZLFB-UHFFFAOYSA-N 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
XJINZNWPEQMMBV-UHFFFAOYSA-N n-methylhexan-1-amine Chemical compound CCCCCCNC XJINZNWPEQMMBV-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
VKCYHJWLYTUGCC-UHFFFAOYSA-N nonan-2-one Chemical compound CCCCCCCC(C)=O VKCYHJWLYTUGCC-UHFFFAOYSA-N 0.000 description 1
125000001400 nonyl 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])[H] 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
XSHOQLFLPSMAGQ-UHFFFAOYSA-N octane-2,6-dione Chemical compound CCC(=O)CCCC(C)=O XSHOQLFLPSMAGQ-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl 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])[H] 0.000 description 1
HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
125000001979 organolithium group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
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229910052763 palladium Inorganic materials 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
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VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical class [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
230000002997 prostaglandinlike Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229960000948 quinine Drugs 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
229920003987 resole Polymers 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000004904 shortening Methods 0.000 description 1
229920002379 silicone rubber Polymers 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229960001407 sodium bicarbonate Drugs 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
YPPQYORGOMWNMX-UHFFFAOYSA-L sodium phosphonate pentahydrate Chemical class [Na+].[Na+].[O-]P([O-])=O YPPQYORGOMWNMX-UHFFFAOYSA-L 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical class [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
YXXYTGAWNWNKJL-UHFFFAOYSA-M sodium;pyrrolidin-1-ide-2,5-dione Chemical compound [Na+].O=C1CCC(=O)[N-]1 YXXYTGAWNWNKJL-UHFFFAOYSA-M 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
241000894007 species Species 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
238000001256 steam distillation Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001382 thioacetal group Chemical group 0.000 description 1
238000006719 thioacetalization reaction Methods 0.000 description 1
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
150000004072 triols Chemical class 0.000 description 1
229940116269 uric acid Drugs 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
239000006216 vaginal suppository Substances 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA000416726A 1978-01-26 1982-11-30 9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation Expired CA1198420A (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
IT7819616A IT7819616A0 (it)	1978-01-26	1978-01-26	9-deossi-9a-metilene-isosteri della pgi 2.
IT19616A/78		1978-01-26
IT3107378A IT1160370B (it)	1978-12-21	1978-12-21	9-deossi-9a-metilene-isosteri della pgi2
IT31073A/78		1978-12-21
CA000320354A CA1209133A (fr)	1978-01-26	1979-01-26	Isosteres 9-desoxy-9a-methylene de pgi.sub.2 et methode de preparation

Publications (1)

Publication Number	Publication Date
CA1198420A true CA1198420A (fr)	1985-12-24

Family

ID=27166061

Family Applications (5)

Application Number	Title	Priority Date	Filing Date
CA000401256A Expired CA1198417A (fr)	1978-01-26	1982-04-19	9-desoxy-9a-methylene isosteres de pgi in2 xx et procede de preparation
CA000401255A Expired CA1209134A (fr)	1978-01-26	1982-04-19	Isosteres 9-desoxy-9a-methylene de pgi.sub.2 et methode de preparation
CA000416725A Expired CA1198419A (fr)	1978-01-26	1982-11-30	9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation
CA000416726A Expired CA1198420A (fr)	1978-01-26	1982-11-30	9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation
CA000416724A Expired CA1198418A (fr)	1978-01-26	1982-11-30	9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation

Family Applications Before (3)

Application Number	Title	Priority Date	Filing Date
CA000401256A Expired CA1198417A (fr)	1978-01-26	1982-04-19	9-desoxy-9a-methylene isosteres de pgi in2 xx et procede de preparation
CA000401255A Expired CA1209134A (fr)	1978-01-26	1982-04-19	Isosteres 9-desoxy-9a-methylene de pgi.sub.2 et methode de preparation
CA000416725A Expired CA1198419A (fr)	1978-01-26	1982-11-30	9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA000416724A Expired CA1198418A (fr)	1978-01-26	1982-11-30	9-desoxy-9a-methylene isosteres de pgi.sub.2 et procede de preparation

Country Status (1)

Country	Link
CA (5)	CA1198417A (fr)

1982
- 1982-04-19 CA CA000401256A patent/CA1198417A/fr not_active Expired
- 1982-04-19 CA CA000401255A patent/CA1209134A/fr not_active Expired
- 1982-11-30 CA CA000416725A patent/CA1198419A/fr not_active Expired
- 1982-11-30 CA CA000416726A patent/CA1198420A/fr not_active Expired
- 1982-11-30 CA CA000416724A patent/CA1198418A/fr not_active Expired

Also Published As

Publication number	Publication date
CA1209134A (fr)	1986-08-05
CA1198419A (fr)	1985-12-24
CA1198418A (fr)	1985-12-24
CA1198417A (fr)	1985-12-24

Legal Events

Date	Code	Title	Description
2002-12-24	MKEX	Expiry

Publication	Publication Date	Title
CA1209133A (fr)	1986-08-05	Isosteres 9-desoxy-9a-methylene de pgi.sub.2 et methode de preparation
CA1181747A (fr)	1985-01-29	Derives de la prostacycline
CA1079725A (fr)	1980-06-17	Analogues de la prostaglandine-acetylene et procede de production
EP0084856A1 (fr)	1983-08-03	Dérivés de la 5,6,7-trinor-4,8-inter-m-phenylène-prostaglandine I2
JPH0245622B2 (fr)	1990-10-11
CA1088931A (fr)	1980-11-04	Obtention d'intermediaires de la prostaglandine a substitution par un 9-oxo-tetrahydropyranyle
JPS5817746B2 (ja)	1983-04-09	シクロベンタンユウドウタイノセイゾウホウホウ
CA1041495A (fr)	1978-10-31	W-pentanorprostaglandines substituees en 15
CA1223582A (fr)	1987-06-30	Carbacyclines, leur production et leur emploi a titre de medicaments
DE2726857A1 (de)	1977-12-29	9 alpha, 11 alpha-epoxymethano- oder 11 alpha, 9 alpha-epoxymethano-9, 11,15-trideoxy-prostaglandin f-analoga
CA1083569A (fr)	1980-08-12	PREPARATION DE .omega.-NORCYCLOALKYL-13,14- DESHYDROPROSTAGLANDINES
CA1220471A (fr)	1987-04-14	Carbacyclines, leur preparation et leur emploi a titre de medicaments
CA1196632A (fr)	1985-11-12	Analogues de 5,6 - dihydro-prostacycline
JPS5846510B2 (ja)	1983-10-17	１３，１４−デヒドロ−１１−デオキシ−プロスタグランジン及びその製造法
KR840000948B1 (ko)	1984-07-01	PGI_2의 9-데옥시-9a-메틸렌 등배전자체의 제조방법
CA1209134A (fr)	1986-08-05	Isosteres 9-desoxy-9a-methylene de pgi.sub.2 et methode de preparation
CA1189506A (fr)	1985-06-25	Derives du bicyclooctane
JPH0369909B2 (fr)	1991-11-05
EP0038131A2 (fr)	1981-10-21	Composés bicyclooctane, leur préparation, compositions les contenant et leur application thérapeutique
US3836581A (en)	1974-09-17	1-alkoximino-2-(omega-substituted-alkyl)-2-cyclopentenes
NO166442B (no)	1991-04-15	Analogifremgangsmaate for fremstilling av terapeutisk virksomme 8-(lavere alkyl)-bicyclo-(4.2.0)-octanderivater.
CA1085832A (fr)	1980-09-16	Analogues des prostaglandines
JPS5921864B2 (ja)	1984-05-22	フルオロプロスタグランジン及びその製造法
US4271183A (en)	1981-06-02	Bicyclic prostaglandins
JPS5929075B2 (ja)	1984-07-18	新規プロスト−５−エン−１３−イン酸誘導体の製法