DE69211994T2 - Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel - Google Patents

Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel

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Publication number
DE69211994T2
DE69211994T2 DE69211994T DE69211994T DE69211994T2 DE 69211994 T2 DE69211994 T2 DE 69211994T2 DE 69211994 T DE69211994 T DE 69211994T DE 69211994 T DE69211994 T DE 69211994T DE 69211994 T2 DE69211994 T2 DE 69211994T2
Authority
DE
Germany
Prior art keywords
compound
preparation
mmol
mixture
dimethoxyphenyl
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 - Fee Related
Application number
DE69211994T
Other languages
English (en)
Other versions
DE69211994D1 (de
Inventor
Teruhisa Ichihashi
Shiro Kida
Takuji Mizui
Sachio Mori
Shozo Takechi
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.)
Shionogi and Co Ltd
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Shionogi and Co Ltd
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.)
Filing date
Publication date
Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd
Application granted granted Critical
Publication of DE69211994D1 publication Critical patent/DE69211994D1/de
Publication of DE69211994T2 publication Critical patent/DE69211994T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
    • 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
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
    • C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/70—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with ring systems containing two or more relevant rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/22—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one naphthalene or hydrogenated naphthalene ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/64—Oxygen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Furan Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Compounds Of Unknown Constitution (AREA)
  • Steroid Compounds (AREA)

Claims (8)

1. Verbindung der Formel (I):
worin R¹ ein Niederalkyl-, Cycloalkyl-, Cycloalkyl-Niederalkylrest, eine Arylgruppe oder ein Aralkylrest ist, die gegebenenfalls substituiert sind,
R² ein Rest der Formel -COOR' (worin R' ein gegebenenfalls substituierter Niederalkyl- oder Aralkylrest ist), ein Niederalkyl- oder ein halogenierter Niederalkylrest ist, oder
R¹ und R² zusammen mit einer benachbarten Carbonylgruppe einen Cyclohexanonring der Formel:
bilden,
R³ eine gegebenenfalls substituierte Phenylgruppe ist, und
der Ring A ein Benzolkern, der gegebenenfalls substituiert ist, oder ein heterocyclischer Ring ist, der S oder O enthält und gegebenenfalls substituiert ist,
oder deren pharmazeutisch verträgliches Salz.
2. Verbindung nach Anspruch 1, worin R² ein Rest der Formel -COOR' ist, worin R7 wie vorstehend definiert ist.
3. Verbindung nach Anspruch 1 oder 2, worin der Ring A ein Benzolkern ist, der mit drei Methoxygruppen substituiert ist, und R³ eine mit zwei Methoxygruppen substituierte Phenylgruppe ist.
4. 1-(3,4.Dimethoxyphenyl)-3-(3-ethyl-1-oxopentyl)-4-hydroxy-2-methoxycarbonyl- 6,7,8-trimethoxynaphthalin.
5. Verfahren zur Herstellung der Verbindung der Formel (I), umfassend die Additionsreaktion einer Verbindung der Formel (II):
worin der Ring A und R³ wie vorstehend definiert sind, und einer Verbindung der Formel (III):
R¹OC-C C-R² (III)
worin R¹ wie vorstehend definiert ist, und R² ein Rest der Formel -COOR' ist (worin R' ein gegebenenfalls substituierter Niederalkyl- oder Aralkylrest ist).
6. Verfahren zur Herstellung der Verbindung der Formel (I), umfassend die Substitutionsreaktion einer Verbindung der Formel (IV):
[worin R² ein Rest der Formel -COOR' ist (worin R' ein gegebenenfalls substituierter Niederalkyloder Aralkylrest ist), und R³ und der Ring A wie vorstehend definiert sind] und einer Verbindung der Formel (V):
R¹-M (V)
[worin R¹ wie vorstehend definiert ist, und M ein Lithiumatom oder eine Gruppe aus Magnesiumatom-Halogenatom ist].
7. Arzneimittel, das die Verbindung nach einem der Ansprüche 1 bis 4 als pharmazeutischen Wirkstoff enthält.
8. Hypolipidemisches Arzneimittel, das die Verbindung nach einem der Ansprüche 1 bis 4 als pharmazeutischen Wirkstoff enthält.
DE69211994T 1991-10-17 1992-10-15 Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel Expired - Fee Related DE69211994T2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP29811991 1991-10-17
PCT/JP1992/001342 WO1993008155A1 (en) 1991-10-17 1992-10-15 Lignan analog, production thereof, and hypolipidemic drug

Publications (2)

Publication Number Publication Date
DE69211994D1 DE69211994D1 (de) 1996-08-08
DE69211994T2 true DE69211994T2 (de) 1997-02-20

Family

ID=17855421

Family Applications (2)

Application Number Title Priority Date Filing Date
DE69211994T Expired - Fee Related DE69211994T2 (de) 1991-10-17 1992-10-15 Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel
DE69228262T Expired - Fee Related DE69228262D1 (de) 1991-10-17 1992-10-15 Verfahren zum Herstellen von Lignin-Analoga und Ausgangsprodukte dafür

Family Applications After (1)

Application Number Title Priority Date Filing Date
DE69228262T Expired - Fee Related DE69228262D1 (de) 1991-10-17 1992-10-15 Verfahren zum Herstellen von Lignin-Analoga und Ausgangsprodukte dafür

Country Status (12)

Country Link
US (4) US5420333A (de)
EP (2) EP0597107B1 (de)
JP (1) JP2839805B2 (de)
KR (1) KR100252428B1 (de)
AT (2) ATE139990T1 (de)
DE (2) DE69211994T2 (de)
DK (2) DK0701991T3 (de)
ES (2) ES2129733T3 (de)
GR (1) GR3020461T3 (de)
HU (1) HU211296A9 (de)
TW (1) TW209215B (de)
WO (1) WO1993008155A1 (de)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2138264C (en) * 1993-04-16 2004-04-06 Sachio Mori Preparation of compounds of lignan series
FR2707980B1 (fr) * 1993-07-20 1995-09-01 Adir Nouveaux cyclohept[b]indoles et cyclooct[b]indoles, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
AU2353095A (en) * 1994-06-22 1996-01-15 Shionogi & Co., Ltd. Process for producing phthalide compound
ID18046A (id) * 1996-08-20 1998-02-19 Takeda Chemical Industries Ltd Senyawa siklik campuran, pembuatan dan penngunaannya.
JP2002529409A (ja) * 1998-11-12 2002-09-10 アルテオン インコーポレーテッド グルコース及び脂質低下化合物類
KR100352269B1 (ko) * 1999-10-08 2002-09-12 한국생명공학연구원 저밀도 지질 단백질에 대해 항산화 활성을 갖는 리그난계 화합물
FR2800738B1 (fr) 1999-11-04 2002-02-08 Corning Sa Naphtopyranes ayant un substituant perfluoroalkyle en position 5, preparation et compositions et matrices (co)polymeres les renfermant
US6770024B1 (en) * 2000-03-28 2004-08-03 Stony Brook Surgical Innovations, Inc. Implantable counterpulsation cardiac assist device
TWI241195B (en) * 2000-04-10 2005-10-11 Shionogi & Co Preventive agent for bile acidic diarrhea
CA2417492A1 (en) * 2000-08-01 2003-01-28 Shionogi & Co., Ltd. Preventives or remedies for obesity or fatty liver
WO2004033411A1 (ja) * 2002-10-08 2004-04-22 Shionogi & Co., Ltd. エノンエステルの製造法
US7152611B2 (en) * 2002-12-30 2006-12-26 International Tape Partners, Llc Coated multifilament dental devices overcoated with imbedded particulate
GB0307918D0 (en) 2003-04-05 2003-05-14 Astrazeneca Ab Therapeutic use
WO2011150286A2 (en) 2010-05-26 2011-12-01 Satiogen Pharmaceuticals,Inc. Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions
CN104023727B (zh) 2011-10-28 2017-04-05 鲁美纳医药公司 用于治疗小儿胆汁淤积性肝病的胆汁酸再循环抑制剂
CN104023718B (zh) 2011-10-28 2017-04-05 鲁美纳医药公司 用于治疗高胆血症和胆汁淤积性肝病的胆汁酸再循环抑制剂
AU2014229050A1 (en) 2013-03-15 2015-10-22 Lumena Pharmaceuticals Llc Bile acid recycling inhibitors for treatment of Barrett's esophagus and gastroesophageal reflux disease
AU2014228850A1 (en) 2013-03-15 2015-10-29 Lumena Pharmaceuticals Llc Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease
JP2022520121A (ja) 2019-02-12 2022-03-28 ミルム ファーマシューティカルズ インコーポレイテッド 胆汁うっ滞を治療する方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NO170760C (no) * 1985-01-10 1992-12-02 Tanabe Seiyaku Co Analogifremgangsmaate for fremstilling av terapeutisk aktive nafthalenderivater
JPS6310746A (ja) * 1986-07-01 1988-01-18 Tanabe Seiyaku Co Ltd ナフタレン誘導体
JPH0372422A (ja) * 1989-05-16 1991-03-27 Tanabe Seiyaku Co Ltd 抗脂血剤

Also Published As

Publication number Publication date
US5731455A (en) 1998-03-24
US5502216A (en) 1996-03-26
US5449814A (en) 1995-09-12
EP0597107B1 (de) 1996-07-03
DK0701991T3 (da) 1999-09-13
GR3020461T3 (en) 1996-10-31
ATE175954T1 (de) 1999-02-15
EP0597107A4 (de) 1994-02-03
ES2091488T3 (es) 1996-11-01
EP0701991A1 (de) 1996-03-20
ATE139990T1 (de) 1996-07-15
US5420333A (en) 1995-05-30
WO1993008155A1 (en) 1993-04-29
JPH05310634A (ja) 1993-11-22
JP2839805B2 (ja) 1998-12-16
KR930703236A (ko) 1993-11-29
DE69211994D1 (de) 1996-08-08
HU211296A9 (en) 1995-11-28
TW209215B (de) 1993-07-11
DK0597107T3 (da) 1996-07-29
DE69228262D1 (de) 1999-03-04
EP0701991B1 (de) 1999-01-20
ES2129733T3 (es) 1999-06-16
KR100252428B1 (ko) 2000-04-15
EP0597107A1 (de) 1994-05-18

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