JPH0347272B2 - - Google Patents
Info
- Publication number
- JPH0347272B2 JPH0347272B2 JP57032981A JP3298182A JPH0347272B2 JP H0347272 B2 JPH0347272 B2 JP H0347272B2 JP 57032981 A JP57032981 A JP 57032981A JP 3298182 A JP3298182 A JP 3298182A JP H0347272 B2 JPH0347272 B2 JP H0347272B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- pgi
- atom
- methyl ester
- hydrogen atom
- 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 - Lifetime
Links
- -1 sulfonic acid pyridine salt Chemical class 0.000 claims description 301
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 70
- 150000003839 salts Chemical class 0.000 claims description 65
- 150000003815 prostacyclins Chemical class 0.000 claims description 38
- 229910052731 fluorine Inorganic materials 0.000 claims description 34
- 125000001153 fluoro group Chemical group F* 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 15
- 125000002723 alicyclic group Chemical group 0.000 claims description 15
- 238000010511 deprotection reaction Methods 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 150000001768 cations Chemical class 0.000 claims description 11
- 238000005755 formation reaction Methods 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 238000005658 halogenation reaction Methods 0.000 claims description 7
- 239000000010 aprotic solvent Substances 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000012024 dehydrating agents Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 239000003586 protic polar solvent Substances 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 2
- 206010047249 Venous thrombosis Diseases 0.000 claims description 2
- 230000000320 anti-stroke effect Effects 0.000 claims description 2
- 230000002785 anti-thrombosis Effects 0.000 claims description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 238000003683 electrophilic halogenation reaction Methods 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 125000005313 fatty acid group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 210
- 150000001875 compounds Chemical class 0.000 description 126
- 238000003786 synthesis reaction Methods 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 150000004702 methyl esters Chemical class 0.000 description 98
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 94
- 230000015572 biosynthetic process Effects 0.000 description 89
- 239000000243 solution Substances 0.000 description 80
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 77
- 239000000047 product Substances 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 159000000000 sodium salts Chemical class 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 57
- 238000003756 stirring Methods 0.000 description 52
- 239000002904 solvent Substances 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 238000004809 thin layer chromatography Methods 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
- 150000002148 esters Chemical class 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 229940086542 triethylamine Drugs 0.000 description 32
- 239000000203 mixture Substances 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
- 235000019441 ethanol Nutrition 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 239000007864 aqueous solution Substances 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 239000011734 sodium Substances 0.000 description 20
- MLRMIFDEZCZOAE-APIJFGDWSA-N (5r,6r,7s,8s)-5-(hydroxymethyl)-2-(2-phenylethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-6,7,8-triol Chemical compound C1([C@H](O)[C@@H](O)[C@H](O)[C@H](N1C=1)CO)=NC=1CCC1=CC=CC=C1 MLRMIFDEZCZOAE-APIJFGDWSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
- 238000001819 mass spectrum Methods 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 15
- 238000001035 drying Methods 0.000 description 15
- 229910052708 sodium Inorganic materials 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 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 14
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 235000011121 sodium hydroxide Nutrition 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 150000001721 carbon Chemical group 0.000 description 12
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 12
- 229940096017 silver fluoride Drugs 0.000 description 12
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 12
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- KWEKXPWNFQBJAY-UHFFFAOYSA-N (dimethyl-$l^{3}-silanyl)oxy-dimethylsilicon Chemical compound C[Si](C)O[Si](C)C KWEKXPWNFQBJAY-UHFFFAOYSA-N 0.000 description 10
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- HEPKWABQTOCTFQ-CXTOUWENSA-N methyl (5e)-5-[(3ar,4r,5r,6as)-5-hydroxy-4-[(e,3s)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoate Chemical compound O1\C(=C\CCCC(=O)OC)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 HEPKWABQTOCTFQ-CXTOUWENSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 150000007514 bases Chemical class 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- 238000005828 desilylation reaction Methods 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000012025 fluorinating agent Substances 0.000 description 8
- 230000002140 halogenating effect Effects 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000006196 drop Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 150000001218 Thorium Chemical class 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- MIEVPVADSZQEAY-UHFFFAOYSA-K magnesium potassium hydrogen sulfate carbonate Chemical compound [Mg+2].[K+].[O-]C([O-])=O.OS([O-])(=O)=O MIEVPVADSZQEAY-UHFFFAOYSA-K 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 150000003863 ammonium salts Chemical class 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229940093956 potassium carbonate Drugs 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 150000003174 prostaglandin I2 derivatives Chemical class 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 5
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 125000005103 alkyl silyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 230000004531 blood pressure lowering effect Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 238000003682 fluorination reaction Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- ARYZCSRUUPFYMY-UHFFFAOYSA-N methoxysilane Chemical compound CO[SiH3] ARYZCSRUUPFYMY-UHFFFAOYSA-N 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
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- 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 4
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- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- KALQHVHFDXUHMO-UHFFFAOYSA-M sodium fluoride hydrochloride Chemical compound [F-].[Na+].Cl KALQHVHFDXUHMO-UHFFFAOYSA-M 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- IODUDVQDMKBOJC-UHFFFAOYSA-N tert-butyl hypobromite Chemical compound CC(C)(C)OBr IODUDVQDMKBOJC-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 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
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3298182A JPS58150583A (ja) | 1982-03-04 | 1982-03-04 | 新規なハロゲン化プロスタサイクリン類、それらの製造法およびそれらを活性成分とする薬学的組成物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3298182A JPS58150583A (ja) | 1982-03-04 | 1982-03-04 | 新規なハロゲン化プロスタサイクリン類、それらの製造法およびそれらを活性成分とする薬学的組成物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58150583A JPS58150583A (ja) | 1983-09-07 |
| JPH0347272B2 true JPH0347272B2 (es) | 1991-07-18 |
Family
ID=12374048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3298182A Granted JPS58150583A (ja) | 1982-03-04 | 1982-03-04 | 新規なハロゲン化プロスタサイクリン類、それらの製造法およびそれらを活性成分とする薬学的組成物 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58150583A (es) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60243079A (ja) * | 1984-05-18 | 1985-12-03 | Asahi Glass Co Ltd | ７―フルオロプロスタグランジンｉ↓２類を有効成分とする薬剤 |
| US4616034A (en) * | 1985-02-28 | 1986-10-07 | G. D. Searle & Co. | 15(R)-5-fluoroprostacyclins, pharmaceutical compositions and anti-thrombotic method of use thereof |
| CH674363A5 (es) * | 1986-12-01 | 1990-05-31 | Hoffmann La Roche | |
| US4808734A (en) * | 1986-12-01 | 1989-02-28 | Hoffmann-La Roche Inc. | 16-cycloalkyl-7-fluoro-prostacyclins |
| JPH04342530A (ja) * | 1991-04-26 | 1992-11-30 | Teijin Ltd | ７−フルオロプロスタサイクリン類脂肪乳剤 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5799580A (en) * | 1980-10-27 | 1982-06-21 | Chinoin Gyogyszer Es Vegyeszet | 7-substituted pgi2 derivative and manufacture |
| JPS57171988A (en) * | 1981-03-11 | 1982-10-22 | Hoffmann La Roche | Novel fluoroprostacyclins |
| JPS57176978A (en) * | 1981-04-02 | 1982-10-30 | Searle & Co | Prostaglandin derivative |
| JPS57200379A (en) * | 1981-06-03 | 1982-12-08 | Teijin Ltd | Haloprostacyclins and their preparations |
-
1982
- 1982-03-04 JP JP3298182A patent/JPS58150583A/ja active Granted
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5799580A (en) * | 1980-10-27 | 1982-06-21 | Chinoin Gyogyszer Es Vegyeszet | 7-substituted pgi2 derivative and manufacture |
| JPS57171988A (en) * | 1981-03-11 | 1982-10-22 | Hoffmann La Roche | Novel fluoroprostacyclins |
| JPS57176978A (en) * | 1981-04-02 | 1982-10-30 | Searle & Co | Prostaglandin derivative |
| JPS57200379A (en) * | 1981-06-03 | 1982-12-08 | Teijin Ltd | Haloprostacyclins and their preparations |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58150583A (ja) | 1983-09-07 |
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