DK2247580T3 - Quinoxalinonderivater som insulinsekretionsstimulatorer, fremgangsmåder til opnåelse deraf og anvendelse deraf til behandlingen af diabetes - Google Patents

Quinoxalinonderivater som insulinsekretionsstimulatorer, fremgangsmåder til opnåelse deraf og anvendelse deraf til behandlingen af diabetes Download PDF

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DK2247580T3
DK2247580T3 DK09718118.4T DK09718118T DK2247580T3 DK 2247580 T3 DK2247580 T3 DK 2247580T3 DK 09718118 T DK09718118 T DK 09718118T DK 2247580 T3 DK2247580 T3 DK 2247580T3
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ethyl
quinoxaline
quinoxalin
chlorophenyl
fluorophenyl
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DK09718118.4T
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Gérard Botton
Micheline Kergoat
Christine Charon
Samer Elbawab
Eric Valeur
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Merck Patent Gmbh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Ophthalmology & Optometry (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (6)

1. Forbindelse valgt fra følgende forbindelser: 3-(4-chlorphenyl)-l-(2,2-difluorethyl)quinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-cyclopropyl-quinoxalin-2(lH)-on l-butyl-3-(4-fluorphenyl)quinoxalin-2(lH)-on 3-(4-fluorphenyl)-l-(2,2,2-trifluorethyl)quinoxalin-2(lH)-on l-ethyl-6,7-difluor-3-(4-fluorphenyl)quinoxalin-2(lH)-on l-ethyl-6,7-difluor-3-(4-chlorphenyl)quinoxalin-2(lH)-on l-cyclopropyl-3-phenylquinoxalin-2(lH)-on l-ethyl-3-furan-2-yl-quinoxalin-2(lH)-on l-ethyl-5-fluor-3-(4-fluorphenyl)quinoxalin-2(lH)-on l-cyclopropyl-3-(4-fluorphenyl)quinoxalin-2(lH)-on l-butyl-3-(4-chlorphenyl)quinoxalin-2(lH)-on 3-(4-chlorbenzyl)-l-ethyl-quinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-(2,2,2-trifluorethyl)quinoxalin-2(lH)-on l-(2,2,2-trifluorethyl)-3-(4-trifluormethylphenyl)quinoxalin-2(lH)-on l-(2,2-difluorethyl)-3-(4-fluorphenyl)quinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-ethyl-5-fluorquinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-ethyl-quinoxalin-2(lAy)-on 3-(2-chlorphenyl)-l-ethyl-quinoxalin-2(lH)-on l-ethyl-3-(4-fluorphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-methylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-fluor-2-methylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-chlor-2-methylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-trifluormethylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-methansulfonyl-phenyl)quinoxalin-2(lH)-on 3-(2,4-dimethoxy-pyrimldin-5-yl)-l-ethyl-quinoxalin-2(lH)-on l-ethyl-3-(4-ethylphenyl)quinoxalin-2(lH)-on l-ethyl-3-furan-3-yl-quinoxalin-2(lH)-on 3- (3,4-dimethoxyphenyl)-l-ethyl-quinoxalin-2(lH)-on 4- (4-ethyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-benzoesyre l-ethyl-3-(l-methyl-lH-pyrazol-4-yl)quinoxalin-2(lH)-on 3-(3-chlorphenyl)-l-ethyl-quinoxalin-2(lH)-on l-ethyl-3-pyridin-3-yl-quinoxalin-2(lH)-on 3-(2,5-difluorphenyl)-l-ethyl-quinoxalin-2(lH)-on l-ethyl-3-(lH-indol-6-yl)quinoxalin-2(lH)-on l-ethyl-3-(lH-indol-5-yl)quinoxalin-2(lH)-on l-ethyl-3-(4-methylbenzyl)quinoxalin-2(lH)-on l-ethyl-3-(4-morpholin-4-ylphenyl)quinoxalin-2(lH)-on 3-(2,3-dihyd ro-l,4-benzodioxin-6-yl)-l-ethylquinoxalin-2(lH)-on 3-(l,3-benzodioxol-5-yl)-l-ethylquinoxalin-2(lH)-on l-ethyl-3-benzylquinoxalin-2(lH)-on såvel som dens racemiske former, tautomerer, enantiomerer, diastereoisomerer, epimerer og polymorfe, og blandinger deraf, og de farmaceutisk acceptable salte deraf.
2. Forbindelsen ifølge krav 1, valgt fra følgende forbindelser: l-cyclopropyl-3-phenylquinoxalin-2(lH)-on l-ethyl-3-(4-fluor-2-methylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-fluorphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-methylphenyl)quinoxalin-2(lH)-on l-ethyl-3-(4-trifluormethylphenyl)quinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-(2,2-difluorethyl)quinoxalin-2(lH)-on 3-(4-chlorphenyl)-l-ethyl-quinoxalin-2(lH)-on l-ethyl-3-(4-chlor-2-methylphenyl)quinoxalin-2(lH)-on såvel som dens racemiske former, tautomerer, enantiomerer, diastereoisomerer, epimerer og polymorfe, og blandinger deraf, og de farmaceutisk acceptable salte deraf.
3. Forbindelse ifølge krav 1, såvel som dens racemiske former, tautomerer, enantiomerer, diastereoisomerer, epimerer og polymorfe, og blandinger deraf, og de farmaceutisk acceptable salte deraf, til anvendelse til forebyggelsen og/eller behandling af patologier forbundet med hyperglykæmi.
4. Forbindelsen ifølge krav 3, til anvendelse i insulinsekretioninduktion som svar på glucosekoncentration.
5. Forbindelsen ifølge kravene 3 eller 4, til anvendelse i forebyggelsen og/eller behandling af diabetes, type II diabetes, patologier forbundet med metaboliske lidelser, hypercholesteræmi, hyperlipidæmi, der er forøget ved hyperinsulinæmi og hyperglykæmi, dyslipidæmi, fedme, kardiovaskulære sygdomme, omfattende atherosclerose, myokardial iskæmi, og sygdomme valgt fra diabetes-beslægtede mikrovaskulære og makrovaskulære komplikationer, hvilke komplikationer omfatter arterial hypertension, atherosclerose, inflammatoriske processer, mikroangiopati, makroangiopati, retinopati og neuropati, såvel som til anvendelse i reducering af hyperglykæmi.
6. Farmaceutisk sammensætning indeholdende mindst en forbindelse ifølge kravene 1 til 2 og en farmaceutisk acceptabel exipiens.
DK09718118.4T 2008-03-05 2009-01-15 Quinoxalinonderivater som insulinsekretionsstimulatorer, fremgangsmåder til opnåelse deraf og anvendelse deraf til behandlingen af diabetes DK2247580T3 (da)

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EP08004053 2008-03-05
PCT/EP2009/000209 WO2009109258A1 (en) 2008-03-05 2009-01-15 Quinoxalinone derivatives as insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes

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EP (1) EP2247580B1 (da)
JP (1) JP5618837B2 (da)
KR (1) KR101637387B1 (da)
CN (1) CN101952258B (da)
AR (1) AR070797A1 (da)
AU (1) AU2009221327B2 (da)
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IL (1) IL207720A (da)
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MX371331B (es) 2012-04-24 2020-01-27 Vertex Pharma Inhibidores de la proteina cinasa dependiente de acido desoxirribonucleico(adn-pk).
ME03336B (me) 2013-03-12 2019-10-20 Vertex Pharma Inhibitori dnk-pk
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MX383072B (es) 2015-12-24 2025-03-13 Univ California Reguladores del cftr y métodos para su uso
JP6894902B2 (ja) 2015-12-24 2021-06-30 ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア Ｃｆｔｒ制御因子及びこの使用方法
ES2913051T3 (es) * 2015-12-24 2022-05-31 Univ California Reguladores de CFTR y métodos de uso de los mismos
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JP2020531511A (ja) 2017-08-24 2020-11-05 ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア 眼球用医薬組成物
CN109796417A (zh) * 2019-01-14 2019-05-24 北京理工大学 一系列喹喔啉酮衍生物的结构、制备方法及用途
CN109793739A (zh) * 2019-01-14 2019-05-24 北京理工大学 一种喹喔啉酮衍生物的结构、制备方法及用途
CN114907323B (zh) * 2022-05-31 2023-08-15 内蒙古民族大学 喹喔啉酮类化合物及其制备方法和应用
CN114957222B (zh) * 2022-05-31 2023-08-15 内蒙古民族大学 化合物及其制备方法和用途

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US8835634B2 (en) 2014-09-16
BRPI0908406B8 (pt) 2023-02-07
BRPI0908406B1 (pt) 2019-04-09
WO2009109258A1 (en) 2009-09-11
PT2247580E (pt) 2015-10-19
BRPI0908406A2 (pt) 2015-08-11
US20110015194A1 (en) 2011-01-20
KR101637387B1 (ko) 2016-07-07
CN101952258A (zh) 2011-01-19
CA2717718C (en) 2016-05-31
US8415352B2 (en) 2013-04-09
AU2009221327B2 (en) 2014-03-27
JP2011513343A (ja) 2011-04-28
IL207720A0 (en) 2010-12-30
EA201001407A1 (ru) 2011-06-30
EP2247580A1 (en) 2010-11-10
AU2009221327A1 (en) 2009-09-11
JP5618837B2 (ja) 2014-11-05
MX2010009576A (es) 2010-09-24
EA021904B1 (ru) 2015-09-30
HUE027811T2 (en) 2016-11-28
CA2717718A1 (en) 2009-09-11
KR20100123899A (ko) 2010-11-25
ZA201007059B (en) 2011-06-29
AR070797A1 (es) 2010-05-05
US20130123257A1 (en) 2013-05-16
CN101952258B (zh) 2014-03-19
ES2548583T3 (es) 2015-10-19
EP2247580B1 (en) 2015-07-08
IL207720A (en) 2014-12-31

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