WO1994004520A1 - Ascofuranone, et agent hypolipidemique, agent hypoglycemique et inhibiteur de glycation contenant chacun un derive d'ascofuranone en tant qu'ingredient actif - Google Patents

Ascofuranone, et agent hypolipidemique, agent hypoglycemique et inhibiteur de glycation contenant chacun un derive d'ascofuranone en tant qu'ingredient actif Download PDF

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Publication number
WO1994004520A1
WO1994004520A1 PCT/JP1993/001135 JP9301135W WO9404520A1 WO 1994004520 A1 WO1994004520 A1 WO 1994004520A1 JP 9301135 W JP9301135 W JP 9301135W WO 9404520 A1 WO9404520 A1 WO 9404520A1
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WO
WIPO (PCT)
Prior art keywords
group
lower alkyl
ascofuranone
substituted
active ingredient
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.)
Ceased
Application number
PCT/JP1993/001135
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English (en)
Japanese (ja)
Inventor
Tomoyoshi Hosokawa
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.)
Immuno Japan Inc
Original Assignee
Immuno Japan Inc
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
Priority claimed from JP5-18904U external-priority patent/JPH0672848U/ja
Application filed by Immuno Japan Inc filed Critical Immuno Japan Inc
Priority to JP50610094A priority Critical patent/JP3249124B2/ja
Publication of WO1994004520A1 publication Critical patent/WO1994004520A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
    • C07D307/32—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide

Definitions

  • the present invention provides a hypoglycemic agent and a glycation inhibitor containing ascofuranone represented by the following general formula (I) and a derivative thereof as an active ingredient, and a compound represented by the following general formula (II) TECHNICAL FIELD
  • the present invention relates to an ascofuranone derivative and a blood lipid lowering agent containing these as an active ingredient.
  • R is a hydrogen atom, a lower alkylcarbonyl group, a pyridylcarbonyl group, a benzoyl group substituted with one lower alkyl group or a lower alkoxy group, a toluenesulfonyl group, and one Or lower alkyl group substituted with two lower alkyl groups or lower alkoxycarbonyl lower alkyl group, and R 'is low!
  • Alkylcarbonyl group pyridylcarbonyl group, 1 Low Benzyl, toluenesulfonyl, substituted with one or two lower alkyl groups, or rubamoyl, or lower alkoxy groups substituted with lower alkyl or lower alkoxy groups Means a loweryl lower alkyl group.
  • Ascoflanonone is an isoprenoid antibiotic produced by the filamentous fungus Ascochyta visiae, and its specific production method is Japanese Patent Publication No. 56-255. It is described in No. 10 publication. The biological activity of ascoflanon has been described as a serum lipid-lowering effect (Journal of Antibiotics, Vol. 26, p. 681, p. 1973). And “Japan Journal 'ob' Pharmaceuticals", Vol. 25, p. 35, 1979.
  • the present inventors have conducted intensive studies in an attempt to explore the new usefulness of ascofuranone as a drug. As a result, it has been found that ascofranone has an excellent blood glucose lowering effect. I found, it has been discovered that the novel aspcoflanonone derivative represented by the above general formula (II) also has an excellent hypoglycemic effect similarly to aspcoflanonone. In addition, glycemic acid was one of the causes of diabetic complications. The increase in glycated protein tissue and lipoprotein has been noted. It has been discovered that the compound represented by the general formula (I) exhibits a potent glycation inhibitory action.
  • the present invention has the general formula (D)
  • R ′ is a lower alkylcarbonyl group, a pyridyl carbonyl group, a benzoyl group substituted with one lower alkyl group or a lower alkoxy group, and a toluenesulfonyl group. Or a lower alkoxy group substituted with one or two lower alkyl groups, or a lower alkoxycarbonyl lower alkyl group). It relates to a blood ⁇ lipid-lowering agent possessed as an active ingredient.
  • R is a hydrogen atom, a lower alkylcarbonyl group, a pyridylcarbonyl group, a benzoyl group substituted with one lower alkyl group or a lower alkoxy group, a toluenesulfonyl group, Or a lower alkyl group substituted with two or more lower alkyl groups, or a lower alkoxycarbonyl lower alkyl group
  • glycation inhibitors is a hydrogen atom, a lower alkylcarbonyl group, a pyridylcarbonyl group, a benzoyl group substituted with one lower alkyl group or a lower alkoxy group, a toluenesulfonyl group, Or a lower alkyl group substituted with two or more lower alkyl groups, or a lower alkoxycarbonyl lower alkyl group
  • lower alkyl and lower alkoxy mean alkyl having 1 to 6 carbons and alkoxy having 1 to 6 carbons, respectively.
  • the substitution position of the carbonyl on the pyridin ring is 2-position (that is, picolinol) and 3-position.
  • the position of the alkyl group or lower alkoxy group on the benzene ring of the benzyl group may be any of the ortho, meta and para positions.
  • the tonolenth sulfonyl group refers to any one of an ono-toluene-sulfonyl group, a metha-no-lenos-norre-honisle group, and a norat-no-lens-nore-honyl group. Or mean.
  • the compound represented by the general formula ( ⁇ ) is a novel compound, and these compounds are obtained by using ascofuranone as a raw material, for example, an acid halide, an acid anhydride, and in some cases, a cyanate,
  • a reactive derivative of an acid such as an isocyanate is used in the presence of a condensing agent (a tertiary amine such as pyridines, triethylamine, dimethylaniline, alkaline base, etc.) or It is produced by reacting without adding a condensing agent.
  • a condensing agent a tertiary amine such as pyridines, triethylamine, dimethylaniline, alkaline base, etc.
  • Ascofuranone is a compound represented by the general formula (I) wherein R is a hydrogen atom.
  • Excipients or auxiliaries include lactose, sucrose, various types of powder, glucose, cellulose, methylsenorelose, canoleboxime, methylsenololose, magnesium stearate, magnesium Sulphate, talc, vegetable oil, It can be manufactured using lecithin or the like.
  • the glycemic acid inhibitory effect is obtained by adding ascofuranone and its derivatives to a reaction solution containing bovine serum albumin and glucose, culturing for a long time, and producing the acid hydrolysis product of fructose-lysine.
  • the reaction mixture containing ribose, arginine, and lysine was added with ascofuranone and its derivatives, followed by cultivation.
  • Control group 4 6 ⁇ 1 5 2 3 ⁇ 2 4 2 8 8 ⁇ 1 8 Asco frannon 4 8 ⁇ 1 4 0 5 ⁇ 4 8 2 3 9 ⁇ 1 1 ns-2 3 *-17% * Normal Litter
  • Ascofuranone and the novel iscofuranone derivative represented by the formula (II) have excellent hypoglycemic, hypolipidemic and glycemic inhibitory effects, and thus prevent diabetes, arteriosclerosis, etc. It is extremely useful as a therapeutic drug.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On décrit un dérivé d'ascofuranone représenté par la formule générale (II), dans laquelle R1 représente alkylcarbonyle inférieur, pyridylcarbonyle, benzoyle substitué par un groupe alcoxy ou alkyle inférieur, toluènesulfonyle, carbamoyle substitué par un ou deux groupes alkyle inférieur, ou alkyle inférieur substitué par alcoxycarbonyle inférieur; un agent hypolipidémique contenant ledit dérivé comme ingrédient actif; et un agent hypoglycémique ou un inhibiteur de glycation contenant chacun un dérivé d'ascofuranone représenté par la formule générale (I) (dans laquelle R représente hydrogène, alkylcarbonyle inférieur, pyridylcarbonyle, benzoyle substitué par un groupe alcoxy ou alkyle inférieur, toluènesulfonyle, carbamoyle substitué par un ou deux groupes alkyle inférieur, ou alkyle inférieur substitué par alcoxycarbonyle inférieur) comme ingrédient actif. Les composés représentés par les formules générales (I) et (II), grâce à leur excellent effet hypoglycémique, hypolipidémique et inhibiteur de glycation, sont remarquablement indiqués pour prévenir et traiter le diabète, l'artériosclérose, etc.
PCT/JP1993/001135 1992-08-11 1993-08-11 Ascofuranone, et agent hypolipidemique, agent hypoglycemique et inhibiteur de glycation contenant chacun un derive d'ascofuranone en tant qu'ingredient actif Ceased WO1994004520A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP50610094A JP3249124B2 (ja) 1993-02-05 1993-08-11 アスコフラノン及びアスコフラノン誘導体を主成分とする血中脂質低下剤，血糖低下剤並びにグリケイション阻害物

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP4/214124 1992-08-11
JP21412492 1992-08-11
JP5/18904 1993-02-05
JP5-18904U JPH0672848U (ja) 1993-03-23 自立性包装体

Publications (1)

Publication Number Publication Date
WO1994004520A1 true WO1994004520A1 (fr) 1994-03-03

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Application Number Title Priority Date Filing Date
PCT/JP1993/001135 Ceased WO1994004520A1 (fr) 1992-08-11 1993-08-11 Ascofuranone, et agent hypolipidemique, agent hypoglycemique et inhibiteur de glycation contenant chacun un derive d'ascofuranone en tant qu'ingredient actif

Country Status (1)

Country Link
WO (1) WO1994004520A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000053563A1 (fr) * 1999-03-11 2000-09-14 Nuclear Receptor Research Limited Nouveaux ligands de recepteurs nucleaires ppar
WO2003063849A1 (fr) * 2002-01-31 2003-08-07 Arigen, Inc. Composition pharmaceutique destinee au diagnostic, a la prevention ou au traitement d'un syndrome multifactoriel
JP2005112755A (ja) * 2003-10-06 2005-04-28 Arigen Inc フェノール系誘導体を有効成分とするクリプトスポリジウム症の予防・治療剤
US6919326B1 (en) 1998-08-24 2005-07-19 Toshio Miyata Carbonyl-stress improving agent and peritoneal dialysate
US7622598B2 (en) * 2003-10-17 2009-11-24 Arigen Pharmaceuticals, Inc. Phenol derivatives and antitrypanosoma preventive/therapeutic agent comprising the same as active ingredient

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5136450A (en) * 1974-09-20 1976-03-27 Chugai Pharmaceutical Co Ltd Asukofuranonjudotai no seiho
GB1498334A (en) * 1976-03-19 1978-01-18 Okada M Ascofuranone derivative and process for preparing the sam

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5136450A (en) * 1974-09-20 1976-03-27 Chugai Pharmaceutical Co Ltd Asukofuranonjudotai no seiho
GB1498334A (en) * 1976-03-19 1978-01-18 Okada M Ascofuranone derivative and process for preparing the sam

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6919326B1 (en) 1998-08-24 2005-07-19 Toshio Miyata Carbonyl-stress improving agent and peritoneal dialysate
US7297689B2 (en) 1998-08-24 2007-11-20 Kiyoshi Kurokawa Method for preparing peritoneal dialysate
EP2070535A1 (fr) 1998-08-24 2009-06-17 Kurokawa, Kiyoshi Médicaments pour décharger le stress carbonyle et les dialysats péritonéaux
WO2000053563A1 (fr) * 1999-03-11 2000-09-14 Nuclear Receptor Research Limited Nouveaux ligands de recepteurs nucleaires ppar
WO2003063849A1 (fr) * 2002-01-31 2003-08-07 Arigen, Inc. Composition pharmaceutique destinee au diagnostic, a la prevention ou au traitement d'un syndrome multifactoriel
JP2005112755A (ja) * 2003-10-06 2005-04-28 Arigen Inc フェノール系誘導体を有効成分とするクリプトスポリジウム症の予防・治療剤
US7622598B2 (en) * 2003-10-17 2009-11-24 Arigen Pharmaceuticals, Inc. Phenol derivatives and antitrypanosoma preventive/therapeutic agent comprising the same as active ingredient
KR101161188B1 (ko) * 2003-10-17 2012-07-02 아리젠 세이야쿠 가부시키가이샤 신규 페놀 유도체 및 그들을 유효 성분으로 하는항트리파노소마 예방ㆍ치료제

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