JPS58150583A - 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 - Google Patents
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Info
- Publication number
- JPS58150583A JPS58150583A JP3298182A JP3298182A JPS58150583A JP S58150583 A JPS58150583 A JP S58150583A JP 3298182 A JP3298182 A JP 3298182A JP 3298182 A JP3298182 A JP 3298182A JP S58150583 A JPS58150583 A JP S58150583A
- Authority
- JP
- Japan
- Prior art keywords
- halogenated
- reaction
- represented
- following formula
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000004480 active ingredient Substances 0.000 title claims description 17
- 150000003815 prostacyclins Chemical class 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- -1 (substituted)phenyl Chemical group 0.000 claims abstract description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 32
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 230000002140 halogenating effect Effects 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 47
- 239000000203 mixture Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000001153 fluoro group Chemical group F* 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 239000003960 organic solvent Substances 0.000 claims description 17
- 238000005658 halogenation reaction Methods 0.000 claims description 16
- 150000007514 bases Chemical class 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 238000005755 formation reaction Methods 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 10
- 239000012025 fluorinating agent Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical group [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 229940096017 silver fluoride Drugs 0.000 claims description 8
- 241000272814 Anser sp. Species 0.000 claims description 7
- 230000003197 catalytic effect Effects 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical group CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 7
- 230000002792 vascular Effects 0.000 claims description 7
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 239000012024 dehydrating agents Substances 0.000 claims description 6
- 229910052709 silver Inorganic materials 0.000 claims description 6
- 239000004332 silver Substances 0.000 claims description 6
- 206010027476 Metastases Diseases 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 238000002054 transplantation Methods 0.000 claims description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 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
- 239000003586 protic polar solvent Substances 0.000 claims description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- ZKLFRQSZDUSMQE-UHFFFAOYSA-N 5,5-dichloroimidazolidine-2,4-dione Chemical compound ClC1(Cl)NC(=O)NC1=O ZKLFRQSZDUSMQE-UHFFFAOYSA-N 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
- 208000001953 Hypotension Diseases 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 230000000320 anti-stroke effect Effects 0.000 claims description 2
- 230000002785 anti-thrombosis Effects 0.000 claims description 2
- 229940124577 antithrombocytopenic agent Drugs 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 239000004067 bulking agent Substances 0.000 claims description 2
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 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
- 238000003683 electrophilic halogenation reaction Methods 0.000 claims description 2
- 230000036543 hypotension Effects 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 238000007631 vascular surgery Methods 0.000 claims description 2
- 230000024883 vasodilation Effects 0.000 claims description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims 4
- SCTINZGZNJKWBN-UHFFFAOYSA-M mercury(1+);fluoride Chemical compound [Hg]F SCTINZGZNJKWBN-UHFFFAOYSA-M 0.000 claims 2
- 238000006011 modification reaction Methods 0.000 claims 2
- 235000003270 potassium fluoride Nutrition 0.000 claims 2
- 239000011698 potassium fluoride Substances 0.000 claims 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims 2
- 206010059245 Angiopathy Diseases 0.000 claims 1
- 241001070941 Castanea Species 0.000 claims 1
- 235000014036 Castanea Nutrition 0.000 claims 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 1
- 208000034189 Sclerosis Diseases 0.000 claims 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims 1
- 239000003048 aphrodisiac agent Substances 0.000 claims 1
- 230000002509 aphrodisiac effect Effects 0.000 claims 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 230000035939 shock Effects 0.000 claims 1
- 239000011269 tar Substances 0.000 claims 1
- 239000011289 tar acid Substances 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 11
- 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 abstract description 10
- 230000008569 process Effects 0.000 abstract description 8
- 125000002252 acyl group Chemical group 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 7
- 230000004071 biological effect Effects 0.000 abstract description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 abstract description 4
- 125000002723 alicyclic group Chemical group 0.000 abstract description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- 229930195733 hydrocarbon Natural products 0.000 abstract description 2
- 230000000269 nucleophilic effect Effects 0.000 abstract description 2
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 abstract 1
- 210000000481 breast Anatomy 0.000 abstract 1
- 229940124549 vasodilator Drugs 0.000 abstract 1
- 239000003071 vasodilator agent Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 150
- 150000004702 methyl esters Chemical class 0.000 description 135
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 58
- 239000000243 solution Substances 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 45
- 238000003756 stirring Methods 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 159000000000 sodium salts Chemical class 0.000 description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- 235000011121 sodium hydroxide Nutrition 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 150000002084 enol ethers Chemical class 0.000 description 11
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 10
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 10
- 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 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 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 235000010357 aspartame Nutrition 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 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 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 210000003127 knee Anatomy 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 239000004020 conductor Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 125000001288 lysyl group Chemical group 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 229910000831 Steel Inorganic materials 0.000 description 6
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 239000007810 chemical reaction solvent Substances 0.000 description 6
- 239000007789 gas Substances 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
- 230000035484 reaction time Effects 0.000 description 6
- 239000010959 steel Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 241000270666 Testudines Species 0.000 description 5
- 150000003863 ammonium salts Chemical class 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 5
- 239000000052 vinegar Substances 0.000 description 5
- 235000021419 vinegar Nutrition 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000003276 anti-hypertensive effect Effects 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 210000000554 iris Anatomy 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
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- 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 true JPS58150583A (ja) | 1983-09-07 |
| JPH0347272B2 JPH0347272B2 (enrdf_load_stackoverflow) | 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 (enrdf_load_stackoverflow) |
Cited By (4)
| 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 |
| FR2607501A1 (fr) * | 1986-12-01 | 1988-06-03 | Hoffmann La Roche | Nouveaux esters en 11,15 de 7-fluoro-11,15-dihydro pgi2 utiles comme medicaments et procede pour leur preparation |
| FR2607500A1 (fr) * | 1986-12-01 | 1988-06-03 | Hoffmann La Roche | Nouvelles 16-cycloalkyl-7-fluoroprostacyclines ayant un substituant alkyle inferieur ou fluoro en position 16, utiles comme medicaments et intermediaires et procede pour leur preparation |
| 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 |
Cited By (7)
| 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 |
| FR2607501A1 (fr) * | 1986-12-01 | 1988-06-03 | Hoffmann La Roche | Nouveaux esters en 11,15 de 7-fluoro-11,15-dihydro pgi2 utiles comme medicaments et procede pour leur preparation |
| FR2607500A1 (fr) * | 1986-12-01 | 1988-06-03 | Hoffmann La Roche | Nouvelles 16-cycloalkyl-7-fluoroprostacyclines ayant un substituant alkyle inferieur ou fluoro en position 16, utiles comme medicaments et intermediaires et procede pour leur preparation |
| BE1001109A3 (fr) * | 1986-12-01 | 1989-07-18 | F Hoffmann La Roche & Co Sa | Nouvelles prostacyclines. |
| BE1001271A5 (fr) * | 1986-12-01 | 1989-09-12 | Hoffmann La Roche | Nouvelles prostacyclines. |
| AU597128B2 (en) * | 1986-12-01 | 1990-05-24 | F. Hoffmann-La Roche Ag | Novel prostacyclines |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0347272B2 (enrdf_load_stackoverflow) | 1991-07-18 |
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