DK175176B1 - Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion, et farmaceutisk præparat indeholdende forbindelsen, forbindelsen som en aktiv terapeutisk bestanddel og anvendelsen af forbindelsen til fremstilling af et medikament - Google Patents

Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion, et farmaceutisk præparat indeholdende forbindelsen, forbindelsen som en aktiv terapeutisk bestanddel og anvendelsen af forbindelsen til fremstilling af et medikament Download PDF

Info

Publication number
DK175176B1
DK175176B1 DK198804902A DK490288A DK175176B1 DK 175176 B1 DK175176 B1 DK 175176B1 DK 198804902 A DK198804902 A DK 198804902A DK 490288 A DK490288 A DK 490288A DK 175176 B1 DK175176 B1 DK 175176B1
Authority
DK
Denmark
Prior art keywords
compound
pharmaceutically acceptable
methyl
thiazolidinedione
amino
Prior art date
Application number
DK198804902A
Other languages
English (en)
Other versions
DK490288D0 (da
DK490288A (da
Inventor
Richard Mark Hindley
Original Assignee
Beecham Group Plc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27263577&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK175176(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB878720825A external-priority patent/GB8720825D0/en
Priority claimed from GB878727987A external-priority patent/GB8727987D0/en
Priority claimed from GB888802454A external-priority patent/GB8802454D0/en
Application filed by Beecham Group Plc filed Critical Beecham Group Plc
Publication of DK490288D0 publication Critical patent/DK490288D0/da
Publication of DK490288A publication Critical patent/DK490288A/da
Application granted granted Critical
Publication of DK175176B1 publication Critical patent/DK175176B1/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • 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
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D277/38—Nitrogen atoms
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles 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 in position 2
    • C07D277/82—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Pyridine Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Description

i DK 175176 B1
Den foreliggende opfindelse angår forbindelsen ifølge krav 1, forbindelsen som en aktiv terapeutisk bestanddel, et farmaceutisk præparat indeholdende denne forbindelse og anvendelse af denne forbindelse til fremstilling af et medikament til behandling og/eller profylakse af hyperglykæmi.
5 EP patentansøgninger med publikationsnumre 0008203, 0139421, 0155845, 0177353, 0193256, 0207581 og 0208420 angår thiazolidindionderivater, som er beskrevet som havende hypoglykaemisk og hypolipidæmisk aktivitet. Chem. Pharm. Bull 30 (10) 3580-3600 angår også visse thiazolidindionderivater med hypoglykæmiske og 10 hypolipidæmiske aktiviteter.
EP 0 008 203 beskriver visse thiazolidindioner som påstår af have bl.a. hypoglykaemisk effekt. Den foreliggende opfindelse angår en strukturel anderledes thiazolidindion som har forbedreded anti-hyperglykæmiske effekter i forhold til de forbindelser der er beskrevet i 15 EP 0 008 203.
Det har nu overraskende vist sig, at det hidtil ukendte substituerede thiazolidindionderivat udviser forbedret blodglucosesænkende aktivitet og derfor er af potentiel nytte i behandling og/eller profylakse af hyperglykæmi og er af særlig nytte i behandling af type 20 II diabetes.
Forbindelse med formlen (I) kan eksistere i én af flere tautomere former, som alle er omfattet af den foreliggende opfindelse. Det vil forstås, at den foreliggende opfindelse omfatter alle isomere former af forbindelsen og de farmaceutisk acceptable salte deraf, 25 herunder en hvilken som helst stereoisomer form deraf, enten som individuelle isomerer eller som blandinger af isomerer.
Egnede farmaceutisk acceptable salte omfatter salte af thiazolidindiongruppen.
30 Egnede farmaceutisk acceptable salte af thiazolidindiongruppen omfatter metalsalte, især j alkalimetalsalte såsom lithium-, natrium- og kaliumsalte.
Egnede farmaceutisk acceptable solvater omfatter hydrater.
35 Forbindelse kan fremstilles som beskrevet i eksemplerne.
Forbindelse ifølge opfindelsen har nyttige terapeutiske egenskaber.
DK 175176 B1 2 I overensstemmelse hermed, angår den foreliggende opfindelse forbindelsen, eller en tautomer form deraf, og/eller et farmaceutisk acceptabelt salt deraf, og/eller et farmaceutisk acceptabelt solvat deraf, til anvendelse som en aktiv terapeutisk bestanddel.
5 Den foreliggende opfindelse angår således forbindelsen, eller en tautomer form deraf, og/eller et farmaceutisk acceptabelt salt deraf, og/eller et farmaceutisk acceptabelt solvat deraf til anvendelse i behandling af og/eller profylakse af hyperglykæmi.
Forbindelsen, eller en tautomer form deraf og/eller et farmaceutisk acceptabelt salt deraf, 10 og/eller et farmaceutisk acceptabelt solvat deraf, kan administreres per se eller fortrinsvis som et farmaceutisk præparat, der også omfatter en farmaceutisk acceptabel bærer.
I overensstemmelse hermed, angår den foreliggende opfindelse også et farmaceutisk præparat omfattende forbindelsen, eller en tautomer form deraf, eller et farmaceutisk 15 acceptabelt salt deraf, eller et farmaceutisk acceptabelt solvat deraf og en farmaceutisk acceptabel bærer dertil.
I nærværende beskrivelse og krav omfatter udtrykket "farmaceutisk acceptabel" forbindelser, præparater og bestanddele til både human og veterinær anvendelse: fx 20 omfatter udtrykket "farmaceutisk acceptabelt salt" et veterinært acceptabelt salt.
Præparatet kan, om nødvendigt, være i form af en pakning, der følges af skriftlige eller trykte brugsanvisninger.
2S Som regel vil de farmaceutiske præparater ifølge den foreliggende opfindelse være adapteret til oral administration, selv om præparater til administration ved andre ruter, såsom ved injektion og percutan absorption, også er forudset.
Specielt egnede præparater til oral administration er enhedsdosisformer såsom tabletter 30 og kapsler. Andre faste enhedsdosisformer såsom pulvere præsenteret i sachets kan også anvendes.
I overensstemmelse med konventionel farmaceutisk praksis kan bæreren omfatte et fortyndingsmiddel, et fyldstof, en disintegrant, et befugtningsmiddel, et smøremiddel, et 35 farvemiddel, et smagsmiddel eller andet konventionelt hjælpemiddel.
Typiske bærere er fx mikrokrystallinsk cellulose, stivelse, natriumstivelsesglycollat, polyvinylpyrrolidon, polyvinylpolypyrrolidon, magnesiumstearat, natriumlaurylsulfat eller sucrose.
DK 175176 B1 3
Præparatet vil mest hensigtsmæssigt være formuleret i enhedsdosisform. En sådan enhedsdosis vil normalt indeholde en mængde af den aktive bestanddel i området fra 0,1 til 1000 mg, sædvanligvis fra 0,1 til 500 mg, og især fra 0,1 til 250 mg.
5
Den foreliggende opfindelse angår yderligere anvendelsen af forbidenlsen til fremstilling af et medikament til behandling og/eller profylakse af hyperglykæmi i et humant eller ikke-humant pattedyr. Medikament kan administreres i en effektiv ikke-toksisk mængde til et hyperglykæmisk humant eller ikke-humant pattedyr med et sådan behov.
10
Den aktive bestanddel kan hensigtsmæssigt administreres som et farmaceutisk præparat som defineret ovenfor, og dette udgør et særligt aspekt ifølge den foreliggende opfindelse.
Ved behandling og/eller profylakse af hyperglykæmiske mennesker, kan forbindelsen, eller 15 en tautomer form deraf, og/eller et farmaceutisk acceptabelt salt deraf, og/eller et farmaceutisk acceptabelt solvat deraf, indtages i doser såsom de ovenfor beskrevne, 1-6 gange dagligt på en sådan måde, at de totale daglige doser for en voksen på 70 kg generelt vil være i området fra 0,1 til 6000 mg, og sædvanligvis fra ca. 1 til 1500 mg.
20 Ved behandling og/eller profylakse af hyperglykæmiske ikke-humane pattedyr, især hunde, kan den aktive bestanddel administreres oralt, sædvanligvis 1 eller 2 gange dagligt og i en mængde i området fra ca. 0,025 mg/kg til 25 mg/kg, fx 0,1 mg/kg til 20 mg/kg.
De følgende fremstillinger og eksempler illustrerer opfindelsen.
25 FREMSTILLING 1 4-Γ2-(Ν-Μ6ίΐΊνΙ-Ν-(2-Ρ6ηζο1Ιιί3ζοΙνΠ3Γη'ιηο)6ίΐΊθχν1Ρ6ηζ3ΐΡ6ΐ^
J
OO-c-CT
DK 175176 B1 4
En blanding af 4-fluorbenzaldehyd (1,5 g) og 2-[N-methyl-N-(2-ben-zothiazolyl)amino]ethanol (2,4 g) i dimethylsulfoxid (50 ml) indeholdende vandfrit kaliumcarbonat (2 g) blev omrørt ved 100°C i 24 timer. Blandingen blev afkølet til 5 stuetemperatur og sat til vand (300 ml). Den vandige opløsning blev ekstraheret med diethylether (2 x 300 ml). De organiske ekstrakter blev vasket med saltopløsning (1 x 300 ml), tørret (MgS04), filtreret og inddampet til tørhed. Titelforbindelsen blev vundet som et voksagtigt fast stof efter kromatografi pi siiicagel i 1% methanol i dichlormethan.
10 ’H NMR (CDCI3): 6 (PP“> 3,2 (3H, s); 3,8 (2H, t); 4,2 (2H, t); 6,8-7,8 (8H, kompleks); 9,8 (IH, s).
FREMSTILLING 2 15 2-rN-Methvl-N-f2-benzothiazolvnamino1ethanol » cxxx.
»
En blanding af 2-chlorbenzothiazol (8,5 g) og 2-methylaminoethanol (20 ml) blev 25 opvarmet ved 120eC under tryk i et forseglet, glasbeklædt, rustfrit stål reaktionskar i 18 timer. Efter afkøling blev olien sat til vand (100 ml), ekstraheret med dichlormethan (2 x 100 ml), de organiske ekstrakter blev tørret (MgS04), filtreret og inddampet til tørhed. Kromatografi af den tilbageværende olie på siiicagel i 2 1/2% methanol i dichlormethan gav titelforbindelsen, som blev anvendt i fremstilling 1 uden yderligere oprensning.
30 JH NMR (CDCI3): 6 (PPmi 3,15 (3H, s); 3,4-4,0 (4H, m); 4,7 (IH, bred s, udskiftes med D20); 6,8-7,6 (4H, kompleks).
DK 175176 B1 5 FREMSTILLING 3 4-r2-(N-Methvl-N-f2-benzoxazolvnamino)ethoxvlbenzaldehvd 5 »
' . 0><XlX
»
Til en opløsning af 2-[N-methyl-N-(2-benzoxazolyl)amino]ethanol (9,6 g), triphenylphosphin (13,1 g) og 4-hydroxybenzaldehyd (6,1 g) i tørt tetrahydrofuran 15 (150 ml) blev en opløsning af diethylazodicarboxylat (9,0 g) i tørt tetrahydrofuran (30 ml) tilsat drlbevis, under en dyne af nitrogen under omrøring ved stuetemperatur.
Opløsningen blev omrørt natten over ved stuetemperatur, hvorefter opløsningsmidlet blev fjernet under reduceret tryk. Remanensen blev opløst i diethylether (300 ml), filtreret og etheropløsningen blev vasket med fortyndet natriumhydroxidopløsning (200 ml), mættet 20 saltopløsning (200 ml), tørret (MgS04), filtreret og opløsningsmidlet blev afdampet.
Titelforbindelsen (smp. 97-98°C) blev vundet efter kromatografi på silicagel under eluering med dichlormethan.
Ή NMR (CDCI3): s (ppm) 25 3,30 (3H, s); 3,85 (2H, t); 4,30 (2H, t) 6,80-7,85 (8H, kompleks); 9,85 (IH, s).
FREMSTILLING 4 2-rN-Methvl-N-(2-benzoxazolvnaminoIethanol 30 » ^CH-
o 0H
» 35 En opløsning af 2-chlorbenzoxazol (15,4 g) i tørt tetrahydrofuran (50 ml) blev tilsat dråbevis til en isafkølet opløsning af 2-methylaminoethanol (15,0 g) i tørt tetrahydrofuran (100 ml) under omrøring og beskyttelse fra atmosfærisk fugtighed. Blandingen blev omrørt ved 0°C i 1 time, lodes opvarme til stuetemperatur og blev omrørt i yderligere 2 timer. Opløsningsmidlet blev fjernet under reduceret tryk, produktet blev opløst i ethylacetat DK 175176 B1 6 (200 ml) og vasket med saltopløsning (2 x 150 ml). Den organiske fase blev tørret (MgS0<), filtreret og opløsningsmidlet afdampet. Kromatografi af remanensen på silicagel i dichlormethan gav titelforbindelsen (smp. 62-3°C), som blev anvendt i fremstilling 3 uden yderligere oprensning.
5 *H NMR (CDCI3): å (ppm) 3,12 (3H s); 3,4-4,0 (4H, m); 4,7 (IH, s, udskiftes med D20); 6,8-7,4 (4H, kompleks). Fremstilling 5 10 4-[2-(N-Methyl-n-(2-pyridyl)amino)ethoxy]benzaldehyd 15 *
Titelforbindelsen blev fremstillet fra 2-(N-methyl-N-(2-pyridyl)amino)ethanol (8,9 g) og 4- fluorbenzaldehyd ved en lignende fremgangsmåde som den, der er beskrevet i fremstilling 22.
20 ‘H NMR (CDCI3): S (ppm) 3,2 (3H, s); 3,8 (2H, t); 4,2 (2H, t); 6,4 (2H, t); 6,9 (2H, d); 7,3 (IH, kompleks); 7,75 (2H,d); 8,15 (IH,d); 9,9 (IH, s).
25 REFERENCE 1 5- (4-r2-(N-Methvl-N-(2-benzothiazolvnamino'iethoxv'lbenzvn-2.4-thiazol)dindion.
» 35 » 5-(4-[2-(N-Methyl-N-(2-benzothiazolyl)amino)ethoxy]benzyliden)-2,4-thiazolidindion (2 g) i tørt 1,4-dioxan (70 ml) blev reduceret under hydrogen i nærværelse af 10% palladium på trækul (3 g) ved omgivelsestemperatur og atmosfærisk tryk indtil hydrogenoptagelse ophørte. Opløsningen blev filtreret gennem diatoméjord, filterpuden blev vasket grundigt DK 175176 B1 7 med dioxan, og de samlede filtrater blev inddampet til tørhed under vakuum.
Titelforbindelsen (smp. 167-8°C) blev vundet efter krystallisation af methanol.
‘H NMR (DMSO-d6): 8 iPP®) 5 2,9-3,4 (2H, kompleks); 3,25 (3H, s); 3,9 (2H, kompleks); 4,25 (2H, kompleks); 4,8 (IH, • kompleks); 6,8-7,75 (8H, kompleks); 12,0 (IH, s, udskiftes med D20).
* REFERENCE 2 10 5-f4-f2-(N-Methvl-N-f2-benzothiazolvnamino)ethoxv1benzvlidenl-2.4-thiazolidindion » - o
En opløsning af 4-[2-(N-methyl-N-(2-benzothiazolyl)amino)ethoxyJbenzaldehyd (1,9 g) og 2,4-thiazolidindion (0,8 g) i toluen (100 ml) indeholdende en kataytisk mængde 20 piperidiniumacetat blev kogt under tilbagesvaling i et Dean-og-Starkapparat i 2 timer. Blandingen blev afkølet og filtreret, og det filtrerede faste stof blev tørret til opnåelse af titelforbindelsen (smp. 219°C).
'H NMR (DMSO-d6): δ (ppm) 25 3,2 (3H, s); 3,9 (2H, t); 4,35 (2H, t); 6,8-7,7 (10H, kompleks).
DK 175176 B1 8 REFERENCE 3 (5-4-r2-(N-Methvl-N-(2-benzoxazolyl)amino)ethoxv1benzvlidenV2.4-thiazolidindiop 5 » o »
En opløsning af 4-[2-(N-methyl-N-(2-benzoxazolyl)amino)ethoxy]benza1dehyd (1,6 g) og 2.4- thiazolidindion (0,63 g) i toluen (100 ml) indeholdende en katalytisk mængde 15 piperidiniumacetat blev kogt under tilbagesvaling i et Dean-og-Starkapparat i 2 timer.
Blandingen blev afkølet og filtreret til opnåelse af titelforbindelsen (smp. 227-9eC).
‘H NMR (DMSO-d6): 6 <PPm) 3,20 (3H, s); 3,90 (2H, t); 4,30 (2H, t); 6,9-7,75 (10H, kompleks).
20 EKSEMPEL 1 5-(4-r2-(N-Methvl-N-(2-Dvridvl)amino)ethoxvlbenzvl)-2.4-thiazolidindion » 25 _
O
α ^ \ S___/
O
30 »
Titelforbindelsen (smp. 153-5°C; MeOH) blev vundet fra 5-(4-[2-(N-me-thyl-N-(2-pyridyl)amino)ethoxy]benzyliden)-2,4-thiazolidindion ved en lignende fremgangsmåde som den, der er beskrevet i reference l.
35 NMR (DMSO-de): δ (PP*) 2,9-3,4 (2H, kompleks); 3,1 (3H, s); 3,9 (2H, t); 4,15 (2H, t); 4,8 (IH, kompleks); 6.5- 6,85 (2H, kompleks); 6,8 (2H, d); 7,2 (2H, d); 7,5 (IH, kompleks); 8,1 (IH, d); 12,05 (IH, bred s, udskiftes med D20).
DK 175176 B1 9 EKSEMPEL 2 5 5-(4-f2-fN-Methvl-N-(2-pvridvl)amino)ethoxv1benzvliden')-2.4-thiazolidindion * » * o 10 oo^"Cx » 15 Titelforbindelsen smp. 177-9°C) blev vundet fra 4-[2-N-methyl-N-(2- pyridyl)amino)ethoxy]benzaldehyd (3,2 g) og 2,4-thiazolidindion (1,1 g) ved en lignende fremgangsmåde som den, der er beskrevet i reference 4 lH NMR (DMSO-D20) : δ (ppm) 20 3,1 (3H, s); 3,9 (2H, t); 4,2 (2H,t); 6,4-7,5 (7H, kompleks); 7,7 (IH, s); 8,1 (IH, d)
DEMONSRATION AF VIRKNINGEN AF FORBINDELSER
Overvægtige Mus, Oral Glucosetolerancetest.
25 C57bl/6 overvægtige (ob/ob) mus blev fodret med en pulveriseret oxoiddiaet. Efter mindst én uge fortsatte musene på en pulveriseret oxoiddiaet eller blev fodret med en pulveriseret oxoiddiæt indeholdende testforbindelsen. Efter 8 dage på den supplerede diæt blev samtlige mus fastet i 5 timer, inden de fik en oral dosis glucose (3 g/kg). Blodprøver til 30 glucoseanalyse blev taget 0, 45, 90 og 135 minutter efter glucoseadministration, og resultaterne er vist nedenfor som procent reduktion i arealet under blodglucosekurven, « hvor testforbindelsebehandlede grupper er sammenlignet med kontrolgrupperne. 7 mus blev anvendt til hver behandling.
35 Toksikologi
Ingen toksikologiske virkninger blev antydet for nogen af forbindelserne ifølge opfindelsen i de ovennævnte tests.

Claims (5)

1. Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion eller en tautomer form deraf, og/eller et farmaceutisk acceptabelt salt deraf, og/eller et 5 farmaceutisk acceptabelt solvat deraf.
2. Farmaceutisk præparat kendetegnet ved, at det omfatter en forbindelse ifølge krav 1, eller en tautomer form deraf, og/eller et farmaceutisk acceptabelt salt deraf, og/eller et farmaceutisk acceptabelt solvat deraf, og en farmaceutisk acceptabel bærer dertil. 10
3. Forbindelse ifølge krav 1 til anvendelse som en aktiv terapeutisk bestanddel.
4. Forbindelse ifølge krav 3 til anvendelse til behandling og/eller profylakse af hyperglykæmi. 15
5. Anvendelse af en forbindelse ifølge krav 1 til fremstilling af et medikament til behandling og/eller profylakse af hyperglykæmi.
DK198804902A 1987-09-04 1988-09-02 Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion, et farmaceutisk præparat indeholdende forbindelsen, forbindelsen som en aktiv terapeutisk bestanddel og anvendelsen af forbindelsen til fremstilling af et medikament DK175176B1 (da)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB878720825A GB8720825D0 (en) 1987-09-04 1987-09-04 Compounds
GB8720825 1987-09-04
GB878727987A GB8727987D0 (en) 1987-11-30 1987-11-30 Novel compounds
GB8727987 1987-11-30
GB8802454 1988-02-04
GB888802454A GB8802454D0 (en) 1988-02-04 1988-02-04 Compounds

Publications (3)

Publication Number Publication Date
DK490288D0 DK490288D0 (da) 1988-09-02
DK490288A DK490288A (da) 1989-03-05
DK175176B1 true DK175176B1 (da) 2004-06-21

Family

ID=27263577

Family Applications (2)

Application Number Title Priority Date Filing Date
DK198804902A DK175176B1 (da) 1987-09-04 1988-09-02 Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion, et farmaceutisk præparat indeholdende forbindelsen, forbindelsen som en aktiv terapeutisk bestanddel og anvendelsen af forbindelsen til fremstilling af et medikament
DK200001556A DK200001556A (da) 1987-09-04 2000-10-18 Substituerede thiazolidindionderivater

Family Applications After (1)

Application Number Title Priority Date Filing Date
DK200001556A DK200001556A (da) 1987-09-04 2000-10-18 Substituerede thiazolidindionderivater

Country Status (19)

Country Link
US (1) US5002953A (da)
EP (2) EP0842925A1 (da)
JP (6) JP2614497B2 (da)
KR (1) KR0164207B1 (da)
AT (1) ATE186724T1 (da)
AU (1) AU611938B2 (da)
CA (1) CA1328452C (da)
CZ (1) CZ391691A3 (da)
DE (2) DE3856378T2 (da)
DK (2) DK175176B1 (da)
ES (1) ES2137915T3 (da)
GR (1) GR3031873T3 (da)
HK (1) HK1011029A1 (da)
IE (1) IE20000683A1 (da)
LU (1) LU90711I2 (da)
NL (1) NL300034I2 (da)
NZ (1) NZ226027A (da)
PT (1) PT88410B (da)
SG (1) SG59988A1 (da)

Families Citing this family (274)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5232925A (en) * 1987-09-04 1993-08-03 Beecham Group P.L.C. Compounds
EP0842925A1 (en) * 1987-09-04 1998-05-20 Beecham Group Plc Substituted thiazolidinedione derivatives
US5194443A (en) * 1987-09-04 1993-03-16 Beecham Group P.L.C. Compounds
GB8820389D0 (en) * 1988-08-26 1988-09-28 Beecham Group Plc Novel compounds
GB8919434D0 (en) * 1989-08-25 1989-10-11 Beecham Group Plc Novel compounds
GB8919417D0 (en) 1989-08-25 1989-10-11 Beecham Group Plc Novel compounds
US5053420A (en) * 1989-10-13 1991-10-01 Pershadsingh Harrihar A Thiazolidine derivatives for the treatment of hypertension
US5037842A (en) * 1990-06-05 1991-08-06 Pfizer Inc. Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic agents
GB9017218D0 (en) * 1990-08-06 1990-09-19 Beecham Group Plc Novel compounds
GB9023584D0 (en) * 1990-10-30 1990-12-12 Beecham Group Plc Novel compounds
GB9023583D0 (en) * 1990-10-30 1990-12-12 Beecham Group Plc Novel compounds
ATE144142T1 (de) * 1991-01-10 1996-11-15 Transcend Therapeutics Inc Verwendung von thiazolidin-4-carboxylatderivaten zur behandlung von lungenerkrankungen
US5747459A (en) * 1991-02-04 1998-05-05 Nestec, Ltd. Method for insuring adequate intracellular glutathione in tissue
JP3053490B2 (ja) * 1991-02-25 2000-06-19 杏林製薬株式会社 チアゾリジン−２，４−ジオン誘導体とその塩及び製造法
GB9124513D0 (en) * 1991-11-19 1992-01-08 Smithkline Beecham Plc Novel process
NO179246C (no) * 1991-11-20 1996-09-04 Sankyo Co Aromatiske amino-alkoholderivater og mellomprodukter til fremstilling derav
US5589492A (en) * 1992-04-10 1996-12-31 Smithkline Beecham Plc Heterocyclic compounds and their use in the treatment of Type-II diabetes
JPH07505647A (ja) * 1992-04-10 1995-06-22 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー 複素環化合物および２型糖尿病の治療におけるそれらの使用
US5430045A (en) * 1992-04-23 1995-07-04 Free Radical Sciences, Inc. Method of reducing or preventing bone marrow hypoplasia
RU2134686C1 (ru) * 1992-07-03 1999-08-20 Смитклайн Бичам П.Л.С. Гетероциклическое соединение, или его таутомерная форма, и/или фармацевтически приемлемая соль, и/или фармацевтически приемлемый сольват, фармацевтическая композиция, снижающая содержание глюкозы в крови, способ лечения и/или профилактики гипергликемии
US5326770A (en) * 1992-07-17 1994-07-05 The Du Pont Merck Pharmaceutical Company Monoamine oxidase-B (MAO-B) inhibitory 5-substituted 2,4-thiazolidinediones useful in treating memory disorders of mammals
US5306724A (en) * 1992-08-17 1994-04-26 Clintec Nutrition Company Method for preventing and treating atherosclerosis
ES2139633T3 (es) * 1992-08-31 2000-02-16 Sankyo Co Derivados de oxazolidina con propiedades anti-diabetica y anti-obesidad, su preparacion y su utilizacion terapeutica.
GB9218830D0 (en) * 1992-09-05 1992-10-21 Smithkline Beecham Plc Novel compounds
US5741803A (en) * 1992-09-05 1998-04-21 Smithkline Beecham Plc Substituted thiazolidinedionle derivatives
EP0645387A1 (en) * 1993-04-07 1995-03-29 Taiho Pharmaceutical Co., Ltd. Thiazolidine derivative and pharmaceutical composition containing the same
GB9308487D0 (en) * 1993-04-23 1993-06-09 Smithkline Beecham Plc Novel compounds
GB9311661D0 (en) * 1993-06-05 1993-07-21 Smithkline Beecham Plc Novel compounds
GB9311644D0 (en) * 1993-06-05 1993-07-21 Smithkline Beecham Plc Novel compounds
GB9315148D0 (en) * 1993-07-22 1993-09-08 Smithkline Beecham Plc Novel compounds
USRE39384E1 (en) 1993-09-01 2006-11-07 Smithkline Beecham P.L.C. Substituted thiazolidinedione derivatives
US6046222A (en) * 1993-09-15 2000-04-04 Warner-Lambert Company Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
US5478852C1 (en) * 1993-09-15 2001-03-13 Sankyo Co Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus
HU228260B1 (en) * 1993-09-15 2013-02-28 Daiichi Sankyo Company Pharmaceutical compositions to treat impaired glucose tolerance
US5874454A (en) * 1993-09-15 1999-02-23 Warner-Lambert Company Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
US5447712A (en) * 1993-12-09 1995-09-05 Free Radical Sciences Method of reducing cyclophosphamide induced hemorrhagic cystitis
US5480896A (en) * 1994-01-27 1996-01-02 American Home Products Corporation Aralkyl-1,2,4-oxadiazolidine-3,5-diones as antihyperglycemic agents
SG47100A1 (en) * 1994-02-10 1998-03-20 Smithkline Beecham Plc Use of insulin sensitisers for treating renal diseases
RU2151145C1 (ru) * 1994-04-11 2000-06-20 Санкио Компани Лимитед Промежуточное соединение для получения гетероциклических соединений, обладающих антидиабетической активностью
US5594015A (en) * 1994-06-22 1997-01-14 Regents Of The University Of California Thiazolidine derivatives for the treatment of psoriasis
US5703096A (en) 1994-10-07 1997-12-30 Sankyo Company, Limited Oxime derivatives, their preparation and their therapeutic use
US5436373A (en) * 1994-10-26 1995-07-25 Elf Atochem North America, Inc. Process for the preparation of N-benzyl-N-organoaminoalkanol
US5641796A (en) * 1994-11-01 1997-06-24 Eli Lilly And Company Oral hypoglycemic agents
US5827865A (en) * 1995-03-09 1998-10-27 Smithkline Beecham P.L.C. Heterocyclic compounds as pharmaceutical
US5925656A (en) * 1995-04-10 1999-07-20 Dr. Reddy's Research Foundation Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5708012A (en) * 1995-04-28 1998-01-13 Sankyo Company, Limited Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus
IL118474A (en) * 1995-06-01 2001-08-08 Sankyo Co Benzimideol derivatives and pharmaceutical preparations containing them
TW438587B (en) 1995-06-20 2001-06-07 Takeda Chemical Industries Ltd A pharmaceutical composition for prophylaxis and treatment of diabetes
US5798375A (en) * 1995-07-03 1998-08-25 Sankyo Company, Limited Treatment of arteriosclerosis and xanthoma
US5859051A (en) * 1996-02-02 1999-01-12 Merck & Co., Inc. Antidiabetic agents
US6090836A (en) * 1996-02-02 2000-07-18 Merck & Co., Inc. Benzisoxazole-derived antidiabetic compounds
US5847008A (en) * 1996-02-02 1998-12-08 Merck & Co., Inc. Method of treating diabetes and related disease states
US6020382A (en) * 1996-02-02 2000-02-01 Merck & Co., Inc. Method of treating diabetes and related disease states
IL120443A (en) * 1996-03-18 2000-07-16 Sankyo Co Use of an insulin sensitizer for the manufacture of a medicament for the treatment or prophylaxis of pancreatitis
AU708919B2 (en) * 1996-04-04 1999-08-19 Sankyo Company Limited Phenylalkylcarboxylic acid derivatives
ATE231136T1 (de) * 1996-04-09 2003-02-15 Reddys Lab Ltd Dr Thiazolidinedionderivate mit antidiabetischen, hypolipidämischen und antihypertensiven eigenschaften, verfahren zu deren herstellung und pharmazeutischen zusammenstellungen, die sie enthalten
US5919782A (en) * 1996-05-06 1999-07-06 Dr. Reddy's Research Foundation Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
ZA973848B (en) * 1996-05-06 1997-12-02 Reddy Research Foundation Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them.
US5801173A (en) * 1996-05-06 1998-09-01 Dr. Reddy's Research Foundation Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
ZA973850B (en) * 1996-05-06 1997-12-02 Reddy Research Foundation Novel antidiabetic compounds having hypolipidaemic, anti-hypertensive properties, process for their preparation and pharmaceutical compositions containing them.
AU3091197A (en) * 1996-05-16 1997-12-05 Boehringer Mannheim Gmbh New process for preparing troglitazone
CA2257284C (en) * 1996-05-31 2005-10-04 Sankyo Company Limited Remedy for autoimmune diseases
US6372750B2 (en) * 1996-07-01 2002-04-16 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases
US5885997A (en) * 1996-07-01 1999-03-23 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US6114526A (en) * 1996-07-01 2000-09-05 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
USRE39266E1 (en) * 1996-07-01 2006-09-05 Dr. Reddy's Laboratories, Limited Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US5985884A (en) * 1996-07-01 1999-11-16 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
WO1997041120A1 (en) * 1996-07-26 1997-11-06 Dr. Reddy's Research Foundation Thiazolidinedione compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions thereof
US6160000A (en) * 1996-12-23 2000-12-12 Merck & Co., Inc. Antidiabetic agents based on aryl and heteroarylacetic acids
US6090839A (en) * 1996-12-23 2000-07-18 Merck & Co., Inc. Antidiabetic agents
UY24886A1 (es) * 1997-02-18 2001-08-27 Smithkline Beecham Plc Tiazolidindiona
AU774839B2 (en) * 1997-02-18 2004-07-08 Smithkline Beecham Plc Process for the preparation of substituted thiazolidinedione
JP2001514663A (ja) * 1997-03-12 2001-09-11 エスモンド，ロバート ダブリュー． アルツハイマー病を処置または予防するための方法
DE19711616A1 (de) * 1997-03-20 1998-09-24 Boehringer Mannheim Gmbh Verbessertes Verfahren zur Herstellung von Thiazolidindionen
US6313113B1 (en) 1997-04-15 2001-11-06 Reddy-Cheminor, Inc. Heterocyclic compounds having antidiabetic, hypolipidemic and antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US6011031A (en) * 1997-05-30 2000-01-04 Dr. Reddy's Research Foundation Azolidinediones useful for the treatment of diabetes, dyslipidemia and hypertension: process for their preparation and pharmaceutical compositions containing them
GB9711683D0 (en) * 1997-06-05 1997-08-06 Smithkline Beecham Plc Composition
AU8539298A (en) * 1997-06-18 1999-01-04 Smithkline Beecham Plc Treatment of diabetes with thiazolidinedione and sulphonylurea
AU8539398A (en) * 1997-06-18 1999-01-04 Smithkline Beecham Plc Treatment of diabetes with thiazolidinedione and metformin
GB9715306D0 (en) * 1997-07-18 1997-09-24 Smithkline Beecham Plc Novel method of treatment
ID24376A (id) 1997-10-02 2000-07-13 Sankyo Co Turunan-turunan asam amidokarboksilat
GB9721692D0 (en) * 1997-10-13 1997-12-10 Smithkline Beecham Plc Novel treatment
US20010031776A1 (en) * 1997-10-13 2001-10-18 Smithkline Beecham P.L.C. Use of thiazolidinediones for the treatment of hyperglycaemia
GB9721693D0 (en) * 1997-10-13 1997-12-10 Smithkline Beecham Plc Novel treatment
US20020006939A1 (en) * 1997-10-13 2002-01-17 Smithkline Beecham P.L.C. Use of thiazolidinediones for the treatment of hyperglycaemia
GB9723295D0 (en) * 1997-11-04 1998-01-07 Smithkline Beecham Plc Novel process
US7091359B2 (en) 1997-11-04 2006-08-15 Smithkline Beecham Plc Process for the preparation of thiazolidinedione derivatives
HUP9902721A2 (hu) 1997-11-25 1999-12-28 The Procter & Gamble Co. Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület
WO1998045292A1 (en) * 1997-12-02 1998-10-15 Dr. Reddy's Research Foundation Thiazolidinedione and oxazolidinedione derivatives having antidiabetic, hypolipidaemic and antihypertensive properties
EP1036075B1 (en) * 1997-12-02 2004-06-23 Dr. Reddy's Laboratories Ltd. Substituted thiazolidinedione and oxazolidinedione having antidiabetic, hypolipidemia and antihypertensive properties
GB9726563D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
US20020137940A1 (en) * 1997-12-16 2002-09-26 Smithkline Beecham P.L.C. 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt, hydrate as pharmaceutical
US6664278B2 (en) 1997-12-16 2003-12-16 Smithkline Beecham P.L.C. Hydrate of 5-[4-[2-(N-methyl-N-(2-pyridil)amino)ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt
GB9726566D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
GB9726568D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
AU1507799A (en) * 1997-12-16 1999-07-05 Sankyo Company Limited Leukemia remedy
US20040058873A1 (en) * 1998-03-12 2004-03-25 Esmond Robert W. Method for treating or preventing Alzheimer's disease
US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
JP4533534B2 (ja) 1998-06-19 2010-09-01 ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド グリコーゲンシンターゼキナーゼ３のインヒビター
US6613785B2 (en) 1998-07-21 2003-09-02 Smithkline Beecham Plc Use of glucose uptake enhancer for reducing post-ischemic injury of the heart
DK1098639T3 (da) * 1998-07-21 2005-06-13 Smithkline Beecham Plc Anvendelse af glucoseoptagelsesforstærkeren rosiglitazon til reduktion af iskæmiinduceret apoptose af pankreatiske beta-celler, endotelceller og neuronale celler
MA26662A1 (fr) * 1998-07-21 2004-12-20 Smithkline Beecham Plc Derives de thiazolidinedione, compositions pharmaceutiques les contenant et leur utilisation
IN187716B (da) * 1998-09-14 2002-06-15 Reddy Research Foundation
US20040102486A1 (en) * 1998-11-12 2004-05-27 Smithkline Beecham Corporation Novel method of treatment
GB9824893D0 (en) * 1998-11-12 1999-01-06 Smithkline Beckman Corp Novel method of treatment
US20030153607A1 (en) * 1998-11-12 2003-08-14 Smithkline Beecham P.L.C. Novel composition and use
KR100643833B1 (ko) 1998-11-12 2006-11-10 스미스클라인비이참피이엘시이 인슐린 감작제 및 다른 항당뇨병 약제의 개선된 방출을위한 제약 조성물
US20040081697A1 (en) * 1998-11-12 2004-04-29 Smithkline Beecham P.L.C. Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent
AR023700A1 (es) 1998-11-12 2002-09-04 Smithkline Beecham Plc Un procedimiento para preparar una composicion farmaceutica que comprende un sensibilizador de insulina
CA2350599A1 (en) * 1998-11-20 2000-06-02 Genentech, Inc. Method of inhibiting angiogenesis
US6191154B1 (en) 1998-11-27 2001-02-20 Case Western Reserve University Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases
WO2000043006A1 (fr) * 1999-01-19 2000-07-27 Sankyo Company, Limited Inhibiteur de la mort des cellules nerveuses imputable à la cytotoxicité de l'acide glutamique
GB9909075D0 (en) * 1999-04-20 1999-06-16 Smithkline Beecham Plc Novel pharmaceutical
GB9909041D0 (en) * 1999-04-20 1999-06-16 Smithkline Beecham Plc Novel pharmaceutical
US20040248945A1 (en) 1999-04-23 2004-12-09 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
PE20010045A1 (es) * 1999-04-23 2001-03-10 Smithkline Beecham Plc Polimorfo de sal del acido maleico de 5-[4-[2-(n-metil-n-(2-piridil)amino)etoxi]bencil]-tiazolidin-2,4-diona
ES2203453T3 (es) 1999-04-23 2004-04-16 Smithkline Beecham Plc Polimorfo de sal del acido maleico de 5-(4-(2-(n-metil-n-(2-piridil)amino)etoxi)bentil)tiazolidina-2,4-diona.
OA11871A (en) 1999-04-23 2006-03-27 Smithkline Beecham Plc Novel pharmaceutical.
US6869959B1 (en) 1999-04-28 2005-03-22 Institute Of Medicinal Molecular Design Inc. Heterocyclic carboxylic acid derivatives
GB9913782D0 (en) * 1999-06-14 1999-08-11 Smithkline Beecham Plc Novel compounds
DE60032898T2 (de) * 1999-06-18 2007-10-25 Merck & Co., Inc. Arylthiazolidindion- und aryloxazolidinderivate
JP2001072592A (ja) 1999-07-01 2001-03-21 Kyowa Hakko Kogyo Co Ltd テロメラーゼ阻害剤
BR0013375A (pt) * 1999-08-17 2002-07-23 Smithkline Beecham Plc Composições farmacêuticas contendo derivados tiazolidinodiona e processo para sua preparação
AR028299A1 (es) 1999-09-17 2003-05-07 Novartis Ag Una composicion farmaceutica que comprende nateglinida, un proceso para su preparacion y el uso de dicha composicion para la preparacion de un medicamento para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con diabetes.
US6878749B2 (en) 1999-09-17 2005-04-12 Novartis Ag Method of treating metabolic disorders, especially diabetes, or a disease or condition associated with diabetes
US6559188B1 (en) 1999-09-17 2003-05-06 Novartis Ag Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes
MY125516A (en) * 1999-11-16 2006-08-30 Smithkline Beecham Plc Novel composition based on thiazolidinedione and metformin and use
ES2156574B1 (es) * 1999-11-18 2002-02-01 Vita Invest Sa Nuevos derivados de tiazolidindiona como agentes antidiabeticos
PL356769A1 (en) 1999-12-03 2004-07-12 Kyoto Pharmaceutical Industries, Ltd. Novel heterocyclic compounds and salts thereof and medicinal use of the same
HU225919B1 (en) * 1999-12-18 2007-12-28 Richter Gedeon Nyrt Thiazolidine-derivatives, process for their preparation pharmaceutical and intermediates
ES2433476T3 (es) 2000-01-21 2013-12-11 Novartis Ag Combinaciones que contienen inhibidores de la dipeptidilpeptidasa-IV y agentes 5 antidiabéticos
GB0006133D0 (en) * 2000-03-14 2000-05-03 Smithkline Beecham Plc Novel pharmaceutical
US6680387B2 (en) 2000-04-24 2004-01-20 Aryx Therapeutics Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US6958355B2 (en) 2000-04-24 2005-10-25 Aryx Therapeutics, Inc. Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US6768008B2 (en) 2000-04-24 2004-07-27 Aryx Therapeutics Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
EP1284291A4 (en) * 2000-05-25 2005-06-08 Yamanouchi Pharma Co Ltd PROMOTER OF HUMAN PGC-1
GB0014005D0 (en) * 2000-06-08 2000-08-02 Smithkline Beecham Plc Novel pharmaceutical
GB0014969D0 (en) 2000-06-19 2000-08-09 Smithkline Beecham Plc Novel method of treatment
US7078397B2 (en) 2000-06-19 2006-07-18 Smithkline Beecham Corporation Combinations of dipeptidyl peptidase IV inhibitors and other antidiabetic agents for the treatment of diabetes mellitus
GB0019223D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
GB0019228D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
GB0021865D0 (en) * 2000-09-06 2000-10-18 Smithkline Beecham Plc Novel pharmaceutical
GB0021978D0 (en) 2000-09-07 2000-10-25 Smithkline Beecham Plc Novel pharmaceutical
AU2001294673A1 (en) * 2000-09-21 2002-04-02 Aryx Therapeutics Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis
EP1322647A1 (en) * 2000-09-26 2003-07-02 Dr. Reddy's Research Foundation Novel polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt and process for their preparation
US7241895B2 (en) 2000-09-26 2007-07-10 Dr. Reddy's Laboratories Limited Polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino[ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
GB0023970D0 (en) * 2000-09-29 2000-11-15 Smithkline Beecham Plc Novel pharmaceutical
GB0023971D0 (en) * 2000-09-29 2000-11-15 Smithkline Beecham Plc Novel pharmaceutical
GB0029125D0 (en) * 2000-11-29 2001-01-10 Specialistkliniken I Varberg H Novel treatment
US6452014B1 (en) 2000-12-22 2002-09-17 Geron Corporation Telomerase inhibitors and methods of their use
ATE337313T1 (de) 2000-12-22 2006-09-15 Smithkline Beecham Plc 5-4'-2'-(n-methyl-n-(2-pyridyl)amino) ethoxy)benzyl)thiazolidin-2,4-dion mesylatsalz
WO2002051823A1 (en) 2000-12-26 2002-07-04 Torrent Pharmaceuticals Ltd Process for the preparation of rosiglitazone maleate
WO2002051441A1 (fr) * 2000-12-26 2002-07-04 Sankyo Company, Limited Compositions medicinales contenant un diuretique et un agent renforçant la resistance a l'insuline
ES2174748B1 (es) * 2001-01-31 2003-09-16 Vita Lab Nueva sal de tiazolidindiona y sus polimorfos como agentes antidiabeticos y procedimiento para la obtencion de los mismos.
WO2002080936A1 (en) * 2001-04-04 2002-10-17 Ortho Mcneil Pharmaceutical, Inc. Combination therapy comprising glucose reabsorption inhibitors and ppar modulators
US20060047000A1 (en) * 2001-04-24 2006-03-02 Aryx Therapeutics, Inc. Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
PL367639A1 (en) * 2001-05-29 2005-03-07 Kyoto Pharmaceutical Industries, Ltd. Novel heterocyclic compound and medicinal use thereof
EP1398313A4 (en) * 2001-05-29 2005-11-16 Kyoto Pharma Ind NEW HETEROCYCLIC DERIVATIVES AND THEIR MEDICAL USE
JP4152641B2 (ja) * 2001-08-07 2008-09-17 クラシエ製薬株式会社 チアゾリジン誘導体の副作用軽減剤
WO2003029251A1 (en) * 2001-09-28 2003-04-10 Biocon Limited Novel process for the synthesis of thiazolidinedione derivatives
GB0127805D0 (en) * 2001-11-20 2002-01-09 Smithkline Beecham Plc Pharmaceutical composition
AU2002352391A1 (en) * 2001-12-13 2003-06-23 Smithkline Beecham Plc A 5(-4-(2-(n-methyl-n-(2-pyridil)amino)ethoxy)benzyl)thiazolidine-2,4-dione (i) 10-camphorsulphonic acid salt and use against diabetes mellitus
GB0129851D0 (en) * 2001-12-13 2002-01-30 Smithkline Beecham Plc Novel compounds
GB0129871D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0129876D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
WO2003050112A1 (en) * 2001-12-13 2003-06-19 Smithkline Beecham Plc Toluenesulfonate hydrates of a thiazolidinedione derivative
GB0129872D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0130510D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
CA2470075A1 (en) * 2001-12-20 2003-07-03 Teva Pharmaceutical Industries Ltd. Hydrogenation of precursors to thiazolidinedione antihyperglycemics
GB0130509D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0130511D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
AU2002352479A1 (en) * 2001-12-20 2003-07-09 Smithkline Beecham Plc 5- (4- (2- (n-methyl-n- (2-pyridyl) amino) ethoxy) benzyl) thiazolidine-2, 4-dione malic acid salt and use against diabetes mellitus
US7015345B2 (en) * 2002-02-21 2006-03-21 Asahi Kasei Pharma Corporation Propionic acid derivatives
KR100450700B1 (ko) 2002-03-22 2004-10-01 주식회사종근당 티아졸리딘디온 유도체 화합물 및 이를 함유하는 약제학적조성물
US20050119314A1 (en) * 2002-04-05 2005-06-02 Sankyo Company, Limited Pharmaceutical composition comprising an ACAT inhibitor and an insulin resistance reducing agent
ES2259412T3 (es) * 2002-04-29 2006-10-01 Teva Pharmaceutical Industries Ltd. Procedimientos para la preparacion de losartan y losartan potasico.
US8268352B2 (en) 2002-08-05 2012-09-18 Torrent Pharmaceuticals Limited Modified release composition for highly soluble drugs
US8216609B2 (en) 2002-08-05 2012-07-10 Torrent Pharmaceuticals Limited Modified release composition of highly soluble drugs
EP1388352A1 (en) 2002-08-08 2004-02-11 Laboratoires Fournier S.A. Use of a ppar-alpha agonist to treat patients suffering from weight gain associated with a ppar-gamma agonist treatment
US7550590B2 (en) 2003-03-25 2009-06-23 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
WO2004089945A1 (en) * 2003-04-09 2004-10-21 Ranbaxy Laboratories Limited Rosiglitazone derivatives as antidiabetic agents
US20050004179A1 (en) * 2003-05-22 2005-01-06 Pedersen Ward A. Methods and materials for treating, detecting, and reducing the risk of developing Alzheimer's Disease
US7718377B2 (en) * 2003-05-29 2010-05-18 Kyoto Pharmaceutical Industries, Ltd. Insulin resistance curative and method of screening the same
KR20110117731A (ko) * 2003-05-30 2011-10-27 랜박시 래보러터리스 리미티드 치환된 피롤 유도체와 ｈｍｇ―ｃｏ 억제제로서의 이의 용도
FR2858556B1 (fr) * 2003-08-06 2006-03-10 Galenix Innovations Composition pharmaceutique solide dispersible et/ou orodispersible non pelliculee contenant au moins le principe actif metformine, et procede de preparation
ZA200602051B (en) 2003-08-13 2007-10-31 Takeda Pharmaceutical 4-pyrimidone derivatives and their use as peptidyl peptidase inhibitors
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
AU2003269483A1 (en) * 2003-09-10 2005-03-29 Biocon Limited Phosphoric acid salt of 5-((4-(2-(methyl-2-pyridinylamino) ethoxy) phenyl) methyl)- 2,4-thiazolidinedione
AU2003266526A1 (en) * 2003-09-17 2005-04-11 Kaname Kawasugi Medicinal composition
WO2005065654A2 (en) * 2003-12-31 2005-07-21 Alpharma, Inc. Rosiglitazone formulations
US20050163842A1 (en) * 2003-12-31 2005-07-28 Garth Boehm Rosiglitazone and metformin formulations
EP1709038A2 (en) * 2004-01-28 2006-10-11 Usv Limited A process for the preparation of 5- 4- 2- n-methyl -n-(2-pyridyl) amino ethoxy phenyl methyl thiaz olidine-2, 4-dione maleate
AR047541A1 (es) * 2004-02-13 2006-01-25 Sandoz Ag Fosfato de 5-[[4-[2-metil-2-piridinil-amino-etoxi]fenil]metil]-2,4 tiazolidinadiona (rosiglitazona) y sus formas polimorficas
GB2421240A (en) * 2004-12-14 2006-06-21 Sandoz Ag Phosphoric acid salt of rosiglitazone
GB2410948A (en) * 2004-02-13 2005-08-17 Sandoz Ag Novel phosphoric acid salt of rosiglitazone
CN102127053A (zh) * 2004-03-15 2011-07-20 武田药品工业株式会社 二肽基肽酶抑制剂
EP1731170A1 (en) * 2004-03-29 2006-12-13 Sankyo Company, Limited Therapeutic agent for diabetes containing insulin resistance improving agent
GB2413795A (en) 2004-05-05 2005-11-09 Cipla Ltd Process for the preparation of rosiglitazone
CA2566352A1 (en) * 2004-05-12 2005-11-17 Medichem S.A. Process for the preparation of rosiglitazone
CZ296468B6 (cs) * 2004-06-10 2006-03-15 Zentiva, A. S. Sul kyseliny fosforecné s 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidin-2,4-dionema zpusob její prípravy
TW200608967A (en) * 2004-07-29 2006-03-16 Sankyo Co Pharmaceutical compositions containing with diabetic agent
CZ297266B6 (cs) * 2004-09-10 2006-10-11 Zentiva, A. S. Zpusob prípravy rosiglitazonu
CZ297347B6 (cs) * 2004-09-21 2006-11-15 Zentiva, A. S. Zpusob prípravy rosiglitazonu
US20060068010A1 (en) * 2004-09-30 2006-03-30 Stephen Turner Method for improving the bioavailability of orally delivered therapeutics
US20060089387A1 (en) * 2004-10-26 2006-04-27 Le Huang Stabilized pharmaceutical composition comprising antidiabetic agent
US20070190079A1 (en) * 2004-10-29 2007-08-16 Kalypsys, Inc. Methods for the selective modulation of ppar
US20060122232A1 (en) * 2004-12-06 2006-06-08 Development Center For Biotechnology 4-Hydroxyfuroic acid derivatives
US7872124B2 (en) 2004-12-21 2011-01-18 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US20070269486A1 (en) * 2005-03-14 2007-11-22 Conor Medsystems, Llc. Methods and Devices for Reducing Tissue Damage After Ischemic Injury
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel
FR2887442A1 (fr) * 2005-06-28 2006-12-29 Oreal Composes benzyl-1,3-thiazolidine-2,4-diones, leurs utilisations et compositions pour stimuler ou induire la pousse des fibres keratiniques et/ou freiner leur chute
FR2887444A1 (fr) * 2005-06-28 2006-12-29 Oreal Composes benzylidene-1,3-thiazolidine-2,4-diones, leurs utilisations et compositions pour stimuler ou induire la pousse des fibres keratiniques et/ou freiner leur chute et/ou augmenter leur densite.
CN101272805A (zh) * 2005-07-12 2008-09-24 第一三共株式会社 包含PPARγ激动剂的药物组合物
DK1942898T4 (da) * 2005-09-14 2014-06-02 Takeda Pharmaceutical Dipeptidylpeptidase-inhibitorer til behandling af diabetes
KR101368988B1 (ko) * 2005-09-16 2014-02-28 다케다 야쿠힌 고교 가부시키가이샤 디펩티딜 펩티다제 억제제
TW200738266A (en) * 2005-09-29 2007-10-16 Sankyo Co Pharmaceutical agent containing insulin resistance improving agent
AU2006313430B2 (en) * 2005-11-08 2012-09-06 Ranbaxy Laboratories Limited Process for (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- [(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt
TW200730173A (en) * 2005-12-16 2007-08-16 Sankyo Co Pharmaceutical composition enhancing production of adiponectin
AR059790A1 (es) * 2006-03-08 2008-04-30 Medichem Sa Procedimiento para la preparacion de formas polimorficas de 5 - (4 - [2 - (n-metil - n -(2 - piridil)amino)etoxi]benciliden) 2, 4 - tiazolidindiona y una forma polimorfica de maleato de rosiglitazona.
WO2008020314A2 (en) * 2006-03-14 2008-02-21 Ranbaxy Laboratories Limited Statin stabilizing dosage formulations
JP2009531456A (ja) * 2006-03-28 2009-09-03 武田薬品工業株式会社 （ｒ）−３−アミノピペリジン二塩酸塩の調製
US8338480B2 (en) * 2006-03-31 2012-12-25 Wellstat Therapeutics Corporation Combination treatment of metabolic disorders
US7435741B2 (en) * 2006-05-09 2008-10-14 Teva Pharmaceutical Industries, Ltd. 2-N{5-[[4-[2-(methyl-2-pyridinylamino) ethoxy] phenyl]methyl]-2,4-thiazolidinedione} butanedioic acid, methods of preparation and compositions with rosiglitazone maleate
DE202006020710U1 (de) 2006-05-09 2009-12-31 Teva Pharmaceutical Industries Ltd. Zusammensetzungen mit Rosiglitazonmaleat
US20070293546A1 (en) * 2006-06-15 2007-12-20 Srinivasula Reddy Maddula Preparation of rosiglitazone and its salts
HUP0600517A3 (en) * 2006-06-23 2008-10-28 Richter Gedeon Nyrt Process for the production of benzylidene-rosiglitazone base
US20080096900A1 (en) 2006-06-26 2008-04-24 Amgen Inc. Methods for treating atherosclerosis
WO2008010087A2 (en) * 2006-07-14 2008-01-24 Ranbaxy Laboratories Limited Polymorphic forms of an hmg-coa reductase inhibitor and uses thereof
NZ574710A (en) 2006-09-07 2012-02-24 Nycomed Gmbh Combination treatment comprising the PDE4 inhibitor Compound A ((2R,4aR, 10bR)6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1 ,2,3,4,4a,10b-hexahydrophenanthridin-2-ol) for diabetes mellitus
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
PE20081150A1 (es) * 2006-09-13 2008-10-03 Takeda Pharmaceutical Inhibidores de dipetidilpeptidasa
TW200838536A (en) * 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
EP2476418A1 (en) 2006-12-21 2012-07-18 Alphapharm Pty Ltd. Pharmaceutical compound and composition for use in treating type II diabetes comprising rosiglitazone in a specific particle size
WO2008091624A2 (en) * 2007-01-22 2008-07-31 Teva Pharmaceutical Industries Ltd. Polymorphic forms of rosiglitazone hydrobromide and processes for preparation thereof
KR101126383B1 (ko) 2007-02-07 2012-04-12 교와 핫꼬 기린 가부시키가이샤 3환계 화합물
US8093236B2 (en) * 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
CN104163864B (zh) 2007-03-30 2017-08-01 Ambrx公司 经修饰fgf‑21多肽和其用途
MX2009010790A (es) * 2007-04-05 2009-10-29 Daiichi Sankyo Co Ltd Derivados de heteroarilo biciclico fusionados.
US20080249156A1 (en) * 2007-04-09 2008-10-09 Palepu Nageswara R Combinations of statins and anti-obesity agent and glitazones
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
MX354786B (es) 2007-06-04 2018-03-21 Synergy Pharmaceuticals Inc Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
ES2449483T3 (es) 2007-07-26 2014-03-19 Amgen, Inc Enzimas lecitina-colesterol aciltransferasa modificadas
US20090076093A1 (en) * 2007-09-14 2009-03-19 Protia, Llc Deuterium-enriched rosiglitazone
PL384446A1 (pl) * 2008-02-12 2009-08-17 Adamed Spółka Z Ograniczoną Odpowiedzialnością Sól 5-[[4-[2-(metylo-2-pirydynyloamino)etoksy]fenylo]metylo]-2,4-tiazolidynodionu z kwasem malonowym i sposób jej wytwarzania
CA2726917C (en) 2008-06-04 2018-06-26 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2010009319A2 (en) 2008-07-16 2010-01-21 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
EP3081213B1 (en) 2008-08-06 2020-04-01 Kyowa Kirin Co., Ltd. Tricyclic compound
EP2324126B1 (en) 2008-08-12 2014-04-23 Zinfandel Pharmaceuticals, Inc. METHOD OF IDENTIFYING Alzheimer's DISEASE RISK FACTORS
US8846315B2 (en) 2008-08-12 2014-09-30 Zinfandel Pharmaceuticals, Inc. Disease risk factors and methods of use
EP2184055A1 (en) 2008-11-07 2010-05-12 LEK Pharmaceuticals d.d. Process for preparing solid dosage forms of rosiglitazone maleate
US20100144140A1 (en) * 2008-12-10 2010-06-10 Novellus Systems, Inc. Methods for depositing tungsten films having low resistivity for gapfill applications
HUP0800755A2 (en) 2008-12-11 2010-09-28 Richter Gedeon Nyrt Crystalline forms of rosiglitazone
RU2480463C1 (ru) 2009-03-05 2013-04-27 Дайити Санкио Компани, Лимитед Пиридилокси производные, полезные в качестве активатора/модулятора гамма-рецептора, активируемого пролифератором пероксисом (ppar) гамма
DE102009053562A1 (de) 2009-11-18 2011-05-19 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Rosiglitazonsuccinat enthaltende pharmazeutische Zusammensetzung
WO2011120923A1 (en) 2010-03-30 2011-10-06 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising an sglt2 inhibitor and a ppar- gamma agonist and uses thereof
CA2810361A1 (en) 2010-09-07 2012-03-15 Daiichi Sankyo Company, Limited Process for preparing benzoic acid esters
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
US20120094959A1 (en) 2010-10-19 2012-04-19 Bonnie Blazer-Yost Treatment of cystic diseases
MA34828B1 (fr) 2011-01-10 2014-01-02 Zinfandel Pharmaceuticals Inc Procédés et produits médicamenteux destinés au traitement de la maladie d'alzheimer
WO2013018899A1 (ja) 2011-08-03 2013-02-07 協和発酵キリン株式会社 ジベンゾオキセピン誘導体
WO2013068486A1 (en) 2011-11-08 2013-05-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of male infertility
EP2788384B1 (en) 2011-12-08 2017-08-09 Amgen Inc. Agonistic human lcat antigen binding proteins and their use in therapy
US9504679B2 (en) 2011-12-19 2016-11-29 Bjoern Colin Kahrs Pharmaceutical compositions comprising glitazones and Nrf2 activators
US20130158077A1 (en) 2011-12-19 2013-06-20 Ares Trading S.A. Pharmaceutical compositions
WO2014068397A1 (en) 2012-11-05 2014-05-08 Commissariat A L'energie Atomique Et Aux Energies Atlternatives (Cea) Combination of an anti-cancer agent such as a tyrosinekinase inhibitor and a stat5 antagonist, preferably a thiazolidinedione, for eliminating hematologic cancer stem cells in vivo and for preventing hematologic cancer relapse
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en) 2013-03-15 2016-01-20 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
JP6606491B2 (ja) 2013-06-05 2019-11-13 シナジー ファーマシューティカルズ インコーポレイテッド グアニル酸シクラーゼｃの超高純度アゴニスト、その作成および使用方法
CA2926685A1 (en) 2013-10-09 2015-04-16 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines
KR20160094956A (ko) 2013-11-05 2016-08-10 벤-구리온 유니버시티 오브 더 네게브 리서치 앤드 디벨럽먼트 어쏘러티 당뇨병 및 당뇨병으로부터 발생하는 합병증 질환의 치료를 위한 화합물
PL3412302T3 (pl) 2014-10-24 2021-11-02 Bristol-Myers Squibb Company Zmodyfikowane polipeptydy fgf-21 i ich zastosowania
WO2016071727A1 (en) 2014-11-04 2016-05-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the prevention and the treatment of rapidly progressive glomerulonephritis
EP3568134A1 (en) 2017-01-16 2019-11-20 Institut National de la Sante et de la Recherche Medicale (INSERM) Methods and pharmaceutical compositions for reducing cd95- mediated cell motility
GR1010570B (el) * 2022-12-22 2023-11-17 Uni-Pharma Κλεων Τσετης Φαρμακευτικα Εργαστηρια Α.Β.Ε.Ε., 4-(2-(4-((2,4-διοξοθειαζολιδιν-5-υλ)μεθυλ)φαινοξυ) παραγωγα με δραση αναστολης της αυτοταξινης

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5522636A (en) * 1978-08-04 1980-02-18 Takeda Chem Ind Ltd Thiazoliding derivative
EP0842925A1 (en) * 1987-09-04 1998-05-20 Beecham Group Plc Substituted thiazolidinedione derivatives

Also Published As

Publication number Publication date
ATE186724T1 (de) 1999-12-15
LU90711I2 (fr) 2001-03-05
IE20000683A1 (en) 2002-07-24
EP0842925A1 (en) 1998-05-20
ES2137915T3 (es) 2000-01-01
CZ391691A3 (en) 1993-03-17
JPH10194970A (ja) 1998-07-28
US5002953A (en) 1991-03-26
JPH09183772A (ja) 1997-07-15
KR890005095A (ko) 1989-05-11
KR0164207B1 (ko) 1999-01-15
JP2837139B2 (ja) 1998-12-14
JPH01131169A (ja) 1989-05-24
DE3856378D1 (de) 1999-12-23
AU611938B2 (en) 1991-06-27
EP0306228A1 (en) 1989-03-08
HK1011029A1 (en) 1999-07-02
NZ226027A (en) 1992-03-26
AU2173888A (en) 1989-03-09
SG59988A1 (en) 1999-02-22
JPH09183726A (ja) 1997-07-15
JPH09183771A (ja) 1997-07-15
NL300034I1 (nl) 2001-03-01
DK490288D0 (da) 1988-09-02
EP0306228B1 (en) 1999-11-17
PT88410B (pt) 1992-10-30
JP2614497B2 (ja) 1997-05-28
JPH10194971A (ja) 1998-07-28
JP2817840B2 (ja) 1998-10-30
DE10199003I1 (de) 2003-06-12
DK200001556A (da) 2000-10-18
DE3856378T2 (de) 2000-05-11
NL300034I2 (nl) 2001-05-01
DK490288A (da) 1989-03-05
CA1328452C (en) 1994-04-12
DE10199003I2 (da) 2003-09-18
PT88410A (pt) 1989-07-31
GR3031873T3 (en) 2000-02-29

Similar Documents

Publication Publication Date Title
DK175176B1 (da) Forbindelsen 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)-2,4-thiazolidindion, et farmaceutisk præparat indeholdende forbindelsen, forbindelsen som en aktiv terapeutisk bestanddel og anvendelsen af forbindelsen til fremstilling af et medikament
EP0658161B1 (en) Substituted thiazolidinedione derivatives
US5741803A (en) Substituted thiazolidinedionle derivatives
US5391565A (en) Oxazolidine dione derivatives
JPH0283384A (ja) 新規化合物、その製法及びそれを含む医薬組成物
SE451017B (sv) Cinnamylmoranolin-derivat
JPH06502146A (ja) チアゾリジンジオン誘導体
JP3053490B2 (ja) チアゾリジン−２，４−ジオン誘導体とその塩及び製造法
JPH04210683A (ja) チアゾリジン−２，４−ジオン誘導体およびこれを含有する糖尿病合併症治療薬
HU203548B (en) Process for producing benzoxazine derivatives and pharmaceutical compositions containing them
JPH03287584A (ja) 置換アリルアミン誘導体
CA1132983A (fr) Procedes de preparation de nouvelles piperazines monosubstituees
SK391691A3 (sk) Tiazolidindiónové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie
NZ226006A (en) Pyridyl ethanolamine derivatives, animal feedstuffs and medicaments
CA1339902C (en) Novel intermediates for preparing substitudes thiazolidinedione derivatives

Legal Events

Date Code Title Description
CTFF Application for supplementary protection certificate (spc) filed

Spc suppl protection certif: CA 2004 00040

Filing date: 20041221

Expiry date: 20130902

CTFG Supplementary protection certificate (spc) issued

Free format text: PRODUCT NAME: ROSIGLITAZON, FARMACEUTISK ACCEPTABLE SALTE OG SOLVATER DERAF

Spc suppl protection certif: CA 2004 00040

Filing date: 20041221

PUP Patent expired