KR100604699B1 - 베라프로스트와 이의 염을 제조하는 방법 - Google Patents
베라프로스트와 이의 염을 제조하는 방법 Download PDFInfo
- Publication number
- KR100604699B1 KR100604699B1 KR1020047001320A KR20047001320A KR100604699B1 KR 100604699 B1 KR100604699 B1 KR 100604699B1 KR 1020047001320 A KR1020047001320 A KR 1020047001320A KR 20047001320 A KR20047001320 A KR 20047001320A KR 100604699 B1 KR100604699 B1 KR 100604699B1
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- compound
- group
- salt
- salts
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract 3
- 150000003839 salts Chemical class 0.000 title claims description 20
- 238000000034 method Methods 0.000 title claims description 11
- CTPOHARTNNSRSR-APJZLKAGSA-N beraprost Chemical compound O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-APJZLKAGSA-N 0.000 title 1
- 229960002890 beraprost Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- -1 azido- Chemical class 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
- 159000000000 sodium salts Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- MIPAPDLHDVYRRT-UHFFFAOYSA-M (2,6-ditert-butyl-4-methylphenoxy)-bis(2-methylpropyl)alumane Chemical compound CC(C)C[Al](CC(C)C)OC1=C(C(C)(C)C)C=C(C)C=C1C(C)(C)C MIPAPDLHDVYRRT-UHFFFAOYSA-M 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 0 CC(CC#CC)C(C=C[C@@]1[C@]2c3cccc(CCC*)c3O[C@]2C[C@]1O)=O Chemical compound CC(CC#CC)C(C=C[C@@]1[C@]2c3cccc(CCC*)c3O[C@]2C[C@]1O)=O 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- SVGPPTBEUQCAMJ-UHFFFAOYSA-N CC(O)=O.CCOC(C)=O.CC(C)OC(C)C Chemical compound CC(O)=O.CCOC(C)=O.CC(C)OC(C)C SVGPPTBEUQCAMJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- IIRVGTWONXBBAW-UHFFFAOYSA-M disodium;dioxido(oxo)phosphanium Chemical compound [Na+].[Na+].[O-][P+]([O-])=O IIRVGTWONXBBAW-UHFFFAOYSA-M 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003815 prostacyclins Chemical class 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- YPPQYORGOMWNMX-UHFFFAOYSA-L sodium phosphonate pentahydrate Chemical compound [Na+].[Na+].[O-]P([O-])=O YPPQYORGOMWNMX-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Description
Claims (14)
- 하기 화학식(VII)의 화합물을 하기 화학식(VIII)의 화합물과 반응시키고, 수득된 하기 화학식(VI)의 화합물을 하기 화학식(V)의 알데히드로 산화시키고, 상기 수득된 알데히드를 분리하거나 분리하지 않고 하기 화학식(IX)의 포스폰산염과 반응시키고, 수득된 하기 화학식(IV)의 화합물을, 이것의 제 11번 위치에 있는 보호기를 제거함으로써 탈보호시키고, 수득된 하기 화학식(III)의 화합물을 환원시키고, 수득된 하기 화학식(II)의 화합물을 가수분해시키고, 하기 화학식(I)의 산을 분리하고 염기와 반응시켜 염으로 변형시키고 그 염을 분리하거나, 수득된 하기 화학식(I)의 산을 분리하지 않고 염으로 변형시켜 수득된 염을 분리하여, 하기 화학식(I)의 화합물 및 이의 염, 특히 나트륨염을 제조하는 방법:상기 식에서,R1은 메틸 또는 에틸기를 의미하고;R2는 탄소수 1 내지 4개의 선형 또는 분지형 알킬기를 의미하고;R3는 탄소수 1 내지 4개의 선형 또는 분지형 알킬기를 의미하고;
- 제 1항에 있어서, 화학식(VI)의 화합물이 디메틸 술폭시드, 옥살릴 클로라이드 및 트리에틸아민의 혼합물을 사용하여 화학식(V)의 화합물로 산화됨을 특징으로 하는 방법.
- 제 1항에 있어서, 화학식(V)의 알데히드와 화학식(IX)의 포스폰산염이 비티히-호너-엠몬 반응(Witting-Horner-Emmon's reaction)의 조건하에서 반응됨을 특징으로 하는 방법.
- 제 1항에 있어서, 화학식(IV)의 화합물의 경우에 제 11번 위치의 히드록실기의 보호기가 산성 매질 중에서 제거됨을 특징으로 하는 방법.
- 제 1항에 있어서, 화학식(III)의 화합물의 환원이 디이소부틸알루미늄-2,6-디-3차 부틸-4-메틸페녹시드에 의해 수행됨을 특징으로 하는 방법.
- 제 1항에 있어서, 화학식(II)의 화합물이 염기성 매질 중에서 가수분해됨을 특징으로 하는 방법.
- 제 1항에 있어서, 화학식(I)의 산이 이의 나트륨염으로 변형되고 이 염이 분리됨을 특징으로 하는 방법.
- R1이 에틸기이고 R2가 메틸기인 화학식(VI)의 화합물.
- R1이 에틸기이고 R2가 메틸기인 화학식(V)의 화합물.
- R1이 에틸기이고 R2가 메틸기인 화학식(IV)의 화합물.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU0103089A HU227157B1 (en) | 2001-07-30 | 2001-07-30 | Production of beraprost ester by selective oxidation |
HUP0103089 | 2001-07-30 | ||
PCT/HU2002/000074 WO2003011849A1 (en) | 2001-07-30 | 2002-07-25 | Process for the production of beraprost and its salts |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20040043169A KR20040043169A (ko) | 2004-05-22 |
KR100604699B1 true KR100604699B1 (ko) | 2006-07-31 |
Family
ID=90001541
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020047001320A KR100604699B1 (ko) | 2001-07-30 | 2002-07-25 | 베라프로스트와 이의 염을 제조하는 방법 |
Country Status (26)
Country | Link |
---|---|
US (1) | US7005527B2 (ko) |
EP (1) | EP1412342B1 (ko) |
JP (1) | JP4440506B2 (ko) |
KR (1) | KR100604699B1 (ko) |
CN (2) | CN1235896C (ko) |
AT (1) | ATE407127T1 (ko) |
AU (1) | AU2002321670B8 (ko) |
BR (1) | BR0211514A (ko) |
CA (1) | CA2453649C (ko) |
CU (1) | CU23324B7 (ko) |
DE (1) | DE60228724D1 (ko) |
ES (1) | ES2314083T3 (ko) |
HK (2) | HK1068877A1 (ko) |
HR (1) | HRP20040198B1 (ko) |
HU (1) | HU227157B1 (ko) |
IL (2) | IL159814A0 (ko) |
ME (2) | MEP18708A (ko) |
MX (1) | MXPA04000847A (ko) |
NO (1) | NO328695B1 (ko) |
NZ (1) | NZ531264A (ko) |
PL (1) | PL216072B1 (ko) |
RS (1) | RS51314B (ko) |
RU (1) | RU2272033C2 (ko) |
UA (1) | UA75692C2 (ko) |
WO (1) | WO2003011849A1 (ko) |
ZA (1) | ZA200400748B (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20180131596A (ko) * | 2016-04-05 | 2018-12-10 | 키노인 기요기스제르 에스 베기에스제티 테르메크에크 기야라 제트알티. | 광학 활성 베라프로스트의 제조 방법 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0215757D0 (en) * | 2002-07-08 | 2002-08-14 | Cascade Biochem Ltd | Benzoprostacyclin intermediates methods for their preparation and products derived therefrom |
JP6174575B2 (ja) | 2011-06-16 | 2017-08-02 | ラング バイオテクノロジー インコーポレーテッド | ベラプロストの製造方法 |
CN102952107B (zh) * | 2011-08-29 | 2015-10-07 | 上海天伟生物制药有限公司 | 一种高纯度的贝前列素钠及其制备方法和用途 |
WO2013040068A2 (en) * | 2011-09-12 | 2013-03-21 | Irix Pharmaceuticals, Inc. | Process for preparing synthetic prostacyclins |
CN103509044A (zh) * | 2012-06-21 | 2014-01-15 | 上海天伟生物制药有限公司 | 贝前列素钠中间体及其制备方法 |
JP2016512833A (ja) * | 2013-03-15 | 2016-05-09 | ゲームス・ファーマ・インコーポレイテッド | ウイルス感染症の治療薬としてのベラプロスト異性体 |
CN103242274B (zh) * | 2013-05-22 | 2014-11-05 | 孙威 | 一种贝前列素钠化合物及其制备方法 |
EP3145919A4 (en) * | 2014-05-20 | 2018-03-14 | Lung Biotechnology PBC | Methods for producing beraprost and its derivatives |
CN108463457B (zh) * | 2015-08-12 | 2019-06-28 | 联合治疗学有限公司 | 制备贝前列素的方法 |
HU231212B1 (hu) * | 2018-04-16 | 2021-11-29 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. | Eljárás iloprost előállítására |
US10577340B1 (en) | 2018-11-26 | 2020-03-03 | Chirogate International Inc. | Beraprost-314d crystals and methods for preparation thereof |
WO2023276983A1 (ja) * | 2021-06-28 | 2023-01-05 | 大内新興化学工業株式会社 | ベラプロストまたは光学活性体の合成中間体およびその製造方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5931510B2 (ja) * | 1979-09-03 | 1984-08-02 | 東レ株式会社 | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体 |
JPS58124778A (ja) * | 1982-01-20 | 1983-07-25 | Toray Ind Inc | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体 |
JPS59134787A (ja) * | 1983-01-19 | 1984-08-02 | Toray Ind Inc | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体の製造法 |
HU197733B (en) * | 1985-05-29 | 1989-05-29 | Chinoin Gyogyszer Es Vegyeszet | Process for producing ephedrin-salts of 7-oxo-prosta-cyclin derivatives |
CA1284642C (en) * | 1986-03-31 | 1991-06-04 | Hikozo Iwakura | Prostacyclin (pgi ) analogues |
JP2594118B2 (ja) * | 1987-07-01 | 1997-03-26 | 塩野義製薬株式会社 | ベンゾジオキサンプロスタサイクリン類縁体 |
JP2542429B2 (ja) * | 1987-10-27 | 1996-10-09 | 三共株式会社 | オクタヒドロナフタリン置換オキシム誘導体 |
GB8929059D0 (en) * | 1989-12-22 | 1990-02-28 | Leo Pharm Prod Ltd | Chemical compounds |
JP3025056B2 (ja) * | 1991-03-12 | 2000-03-27 | 財団法人微生物化学研究会 | 2,6−ジデオキシ−2−フルオロ−l−タロピラノース誘導体の製造法 |
JP3024298B2 (ja) * | 1991-09-13 | 2000-03-21 | 住友化学工業株式会社 | シクロペンテンエステル類及びその利用 |
JPH09132589A (ja) * | 1995-09-08 | 1997-05-20 | Microbial Chem Res Found | 糖部分の水酸基をモノ−または−ジ−o−アミノアルカノイル化された含フッ素アンスラサイクリン誘導体 |
-
2001
- 2001-07-30 HU HU0103089A patent/HU227157B1/hu unknown
- 2001-12-28 JP JP2001398828A patent/JP4440506B2/ja not_active Expired - Lifetime
-
2002
- 2002-07-25 RU RU2004105959/04A patent/RU2272033C2/ru active
- 2002-07-25 RS YUP-86/04A patent/RS51314B/sr unknown
- 2002-07-25 ME MEP-187/08A patent/MEP18708A/xx unknown
- 2002-07-25 NZ NZ531264A patent/NZ531264A/en not_active IP Right Cessation
- 2002-07-25 ME MEP-2008-187A patent/ME00089B/me unknown
- 2002-07-25 IL IL15981402A patent/IL159814A0/xx active IP Right Grant
- 2002-07-25 CN CNB02815021XA patent/CN1235896C/zh not_active Expired - Lifetime
- 2002-07-25 MX MXPA04000847A patent/MXPA04000847A/es active IP Right Grant
- 2002-07-25 EP EP02755382A patent/EP1412342B1/en not_active Expired - Lifetime
- 2002-07-25 PL PL367298A patent/PL216072B1/pl unknown
- 2002-07-25 DE DE60228724T patent/DE60228724D1/de not_active Expired - Lifetime
- 2002-07-25 UA UA2004021460A patent/UA75692C2/uk unknown
- 2002-07-25 AT AT02755382T patent/ATE407127T1/de not_active IP Right Cessation
- 2002-07-25 US US10/484,209 patent/US7005527B2/en not_active Expired - Lifetime
- 2002-07-25 CA CA002453649A patent/CA2453649C/en not_active Expired - Lifetime
- 2002-07-25 ES ES02755382T patent/ES2314083T3/es not_active Expired - Lifetime
- 2002-07-25 WO PCT/HU2002/000074 patent/WO2003011849A1/en active IP Right Grant
- 2002-07-25 AU AU2002321670A patent/AU2002321670B8/en not_active Ceased
- 2002-07-25 BR BR0211514-0A patent/BR0211514A/pt active Search and Examination
- 2002-07-25 CN CNB2005100702984A patent/CN100347165C/zh not_active Expired - Lifetime
- 2002-07-25 KR KR1020047001320A patent/KR100604699B1/ko active IP Right Grant
-
2004
- 2004-01-11 IL IL159814A patent/IL159814A/en unknown
- 2004-01-26 CU CU20040014A patent/CU23324B7/es unknown
- 2004-01-29 ZA ZA2004/00748A patent/ZA200400748B/en unknown
- 2004-01-29 NO NO20040388A patent/NO328695B1/no not_active IP Right Cessation
- 2004-02-27 HR HR20040198A patent/HRP20040198B1/xx not_active IP Right Cessation
-
2005
- 2005-02-16 HK HK05101229A patent/HK1068877A1/xx not_active IP Right Cessation
- 2005-11-25 HK HK05110705A patent/HK1078857A1/xx not_active IP Right Cessation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20180131596A (ko) * | 2016-04-05 | 2018-12-10 | 키노인 기요기스제르 에스 베기에스제티 테르메크에크 기야라 제트알티. | 광학 활성 베라프로스트의 제조 방법 |
KR102373051B1 (ko) | 2016-04-05 | 2022-03-11 | 키노인 기요기스제르 에스 베기에스제티 테르메크에크 기야라 제트알티. | 광학 활성 베라프로스트의 제조 방법 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20040171873A1 (en) | Process for the preparation of 17-phenyl-18,19,20-thinor-pgf 2a and its derivatives | |
KR100604699B1 (ko) | 베라프로스트와 이의 염을 제조하는 방법 | |
US6927300B2 (en) | Process for the preparation of Latanoprost | |
EP0038614A2 (en) | Esters of 5- and 6-oxo-prostaglandins | |
JPH0859662A (ja) | N−9置換グアニン化合物の調製 | |
JPH09328498A (ja) | 24,25−ジヒドロキシコレステロールの製造法およびその合成中間体 | |
JPH0141142B2 (ko) | ||
HU200173B (en) | Process for producing intermediary products of prostaglandin analogs | |
JPH029585B2 (ko) | ||
JPH023793B2 (ko) | ||
JP2940395B2 (ja) | オキシグルタル酸エステル誘導体の製法 | |
JP3673603B2 (ja) | 光学活性2,4,4−トリメチル−2−シクロヘキセン−1−オール及びそのエステル類の製造方法 | |
KR100241263B1 (ko) | N-알킬옥시카르보닐-베타-알킬술포닐발린 화합물의 제조방법 | |
JPH0124782B2 (ko) | ||
JP4386581B2 (ja) | 精製されたプロスタグランジン誘導体の製造方法 | |
JP2991774B2 (ja) | プロパルギルアルコールの新規合成法および該アルコールのプロスタグランジン前駆物質を製造するための使用 | |
FR2494696A1 (fr) | Nouveau procede de preparation de steroides 3-amines et leurs sels | |
KR960015405B1 (ko) | 프로스타글란딘 중간체 화합물의 제조방법 | |
US4042606A (en) | Substituted phenyl esters of PGA2 | |
JPH0141146B2 (ko) | ||
JP4157175B2 (ja) | 2′−ピロリジンプロパン酸誘導体の製造方法 | |
JPH0220616B2 (ko) | ||
WO2002060850A1 (fr) | Procede de synthese d'acide gras insature $g(a)-cetol | |
JPH026755B2 (ko) | ||
JPH0141145B2 (ko) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20130702 Year of fee payment: 8 |
|
FPAY | Annual fee payment |
Payment date: 20140704 Year of fee payment: 9 |
|
FPAY | Annual fee payment |
Payment date: 20150630 Year of fee payment: 10 |
|
FPAY | Annual fee payment |
Payment date: 20160706 Year of fee payment: 11 |
|
FPAY | Annual fee payment |
Payment date: 20170616 Year of fee payment: 12 |
|
FPAY | Annual fee payment |
Payment date: 20190617 Year of fee payment: 14 |