[go: up one dir, main page]

EP1423113A1 - Composes de liaison au recepteur nucleaire nr1h4 - Google Patents

Composes de liaison au recepteur nucleaire nr1h4

Info

Publication number
EP1423113A1
EP1423113A1 EP02750474A EP02750474A EP1423113A1 EP 1423113 A1 EP1423113 A1 EP 1423113A1 EP 02750474 A EP02750474 A EP 02750474A EP 02750474 A EP02750474 A EP 02750474A EP 1423113 A1 EP1423113 A1 EP 1423113A1
Authority
EP
European Patent Office
Prior art keywords
substituted
compound
alkyl
alkylphenyl
phenyl
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
EP02750474A
Other languages
German (de)
English (en)
Other versions
EP1423113A4 (fr
Inventor
Ulrike Bauer
Zach Cheruvallath
Ulrich Deuschle
Elena Dneprovskaia
Tim Gahman
Kristina Giegrich
Ronnie Hanecak
Normand Hebert
John Kiely
Ingo Kober
Manfred Kogl
Harald Kranz
Claus Kremoser
Matthew Lee
Kerstin Otte
Carlton Sage
Manish Sud
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.)
Phenex Pharmaceuticals AG
Original Assignee
Lion Bioscience AG
Phenex Pharmaceuticals AG
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 EP01119473A external-priority patent/EP1285914B1/fr
Application filed by Lion Bioscience AG, Phenex Pharmaceuticals AG filed Critical Lion Bioscience AG
Priority to EP02750474A priority Critical patent/EP1423113A4/fr
Publication of EP1423113A1 publication Critical patent/EP1423113A1/fr
Publication of EP1423113A4 publication Critical patent/EP1423113A4/fr
Ceased legal-status Critical Current

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
    • 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
    • C07D277/02—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
    • C07D277/50—Nitrogen atoms bound to hetero atoms
    • C07D277/52—Nitrogen atoms bound to hetero atoms to sulfur atoms, e.g. sulfonamides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support

Definitions

  • the present invention relates to compounds that bind to the NR1 H4 nuclear receptor and methods of treating diseases or pathological conditions influenced by NR1 H4.
  • the present invention provides, inter alia, novel NR1 H4 nuclear receptor protein binding compounds according to the general formula (I) shown below. These compounds are also binders of mammalian homologues of the receptor. Further the object of the invention is solved by providing for, amongst the NR1 H4 nuclear receptor protein binding, compounds according to the general formula (I) which act as agonists and compounds which act as antagonists of the human FXR receptor or a mammalian homologue thereof.
  • the invention provides for FXR agonists which may be used for the treatment of cholesterol associated conditions or diseases.
  • cholesterol lowering or cholestatic compounds are disclosed.
  • the compounds according to the invention may be used for manufacture of antitumor medicaments and/or for the treatment of diseases such as cancer.
  • the carrier is generally a finely divided solid, which is in a mixture with the finely divided active component.
  • the active compound or combination of active compounds is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.
  • C 7 to C ⁇ 2 substituted phenylalkyl denotes a C 7 to C ⁇ 2 phenylalkyl group substituted on the Ci to C 6 alkyl portion with one or more, and preferably one or two, groups chosen from halogen, hydroxy, protected hydroxy, oxo, protected oxo, amino, protected amino, monosubstituted amino, protected monosubstituted amino, disubstituted amino, guanidino, protected guanidino, heterocyclic ring, substituted heterocyclic ring, d to C 8 alkyl, d to C 8 substituted alkyl, Ci to C 8 alkoxy, Ci to C 8 substituted alkoxy, C 1 to C 8 acyl, Ci to C 8 substituted acyl, Ci to C 8 acyloxy, nitro, carboxy, protected carboxy, carbamoyl, carboxamide, protected carboxamide, N-(C ⁇ to C 6 alkyl)carboxamide,
  • C 7 to C ⁇ 2 substituted phenylalkyl examples include groups such as 2-hydroxyphenylmethyl, 3-hydroxyphenylmethyl, 2- methoxyphenylmethyl, 3-methoxyphenylmethyl, 2,6-difluorophenylmethyl, 2,3- difluorophenylmethyl, 2,6-dichlorophenylmethyl, 2,3-dichlorophenylmethyl, 3,5- dichlorophenylmethyl, 2-hydroxyphenylethyl, 3-hydroxyphenylethyl, 2- methoxyphenylethyl, 3-methoxyphenylethyl, 2,6-difluorophenylethyl, 2,3- difluorophenylethyl, 2,6-dichlorophenylethyl, 2,3-dichlorophenylethyl, 3,5- dichlorophenylmethyl 2-phenyl-1-chloroethyl, 2-(4-methoxyphenyl)ethyl
  • Preferred heterocyclic rings include morpholino, piperidinyl, piperazinyl, 2-amino-imidazoyl, tetrahydrofurano, pyrrolo, tetrahydrothiophen-yl, hexamethyleneimino and heptamethyleneimino.
  • substituted heterocycle or "substituted heterocyclic ring” means the above-described heterocyclic ring is substituted with, for example, one or more, and preferably one or two, substituents which are the same or different which substituents can be halogen, hydroxy, protected hydroxy, cyano, nitro, Ci to C 8 alkyl, Ci to C 8 alkoxy, Ci to C 8 substituted alkoxy, Ci to C 8 acyl, d to C 8 acyloxy, carboxy, protected carboxy, carboxymethyl, protected carboxymethyl, hydroxymethyl, protected hydroxymethyl, amino, protected amino, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino carboxamide, protected carboxamide, N-(d to C 12 alkyl)carboxamide, protected N-(C ⁇ to C 6 alkyl)carboxamide, N, N-di(C ⁇ to
  • substituted naphthyl represents disubstituted naphthyl groups wherein the substituents are different, for example, 3- methyl-4-hydroxynaphth-1 -yl, 3-chloro-4-hydroxynaphth-2-yl, 2-methoxy-4- bromonaphth-1-yl, 4-ethyl-2-hydroxynaphth-1-yl, 3-hydroxy-4-nitronaphth-2-yl, 2- hydroxy-4-chloronaphth-1-yl, 2-methoxy-7-bromonaphth-1-yl, 4-ethyl-5- hydroxynaphth-2-yl, 3-hydroxy-8-nitronaphth-2-yl, 2-hydroxy-5-chloronaphth-1-yl and the like.
  • R 3 and R 4 may be taken together with nitrogen to form a heterocycle or substituted heterocycle of the following kind aziridine, azetidine, pyrrolidine, 3-methylpyrrolidine, 3-aminopyrrolidine, 3-hydroxypyrrolidine, pyrazolidine, imidazolidine, piperidine, 2-methylpiperidine, 4-carboxypiperidine, 4- (carboxymethyl)piperidine, piperazine, morpholine, azepine, and tetrahydroisoquinoline.
  • C to C 8 acyl encompasses groups such as formyl, acetyl, propionyl, butyryl, pentanoyl, pivaloyl, hexanoyl, heptanoyl, benzoyl and the like. Preferred acyl groups are acetyl and benzoyl.
  • Ci to C 8 alkoxy denotes groups such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, t-butoxy and like groups. A preferred alkoxy is methoxy.
  • Ci to C 8 substituted alkoxy means the alkyl portion of the alkoxy can be substituted in the same manner as in relation to Ci to C 8 substituted alkyl.
  • Ci to C 8 substituted aminoacyl denotes the acyl group substituted by one or more, and preferably one or two, halogen, hydroxy, protected hydroxy, oxo, protected oxo, cyclohexyl, naphthyl, amino, protected amino, monosubstituted amino, protected monosubstituted amino, disubstituted amino, guanidino, heterocyclic ring, substituted heterocyclic ring, imidazolyl, indolyl, pyrrolidinyl, Ci to C 8 alkoxy, Ci to C 8 acyl, Ci to C 8 acyloxy, nitro, Ci to C 8 alkyl ester, carboxy, protected carboxy, carbamoyl, carboxamide, protected carboxamide, N-(C ⁇ to C 6 alkyl)carboxamide, protected N-(C ⁇ to C 6 alkyl)carboxamide, N,N-di(C ⁇ to C 6 alkyl)
  • compositions comprising an effective amount of a compound according to the invention.
  • Such compositions can be administered by various routes, for example oral, rectal, subcutaneous, intramuscular, intravenous or intracerebral.
  • the preferred route of administration would be oral at daily doses of the compound for adult human treatment of about 0.01-5000 mg, preferably 1-1500 mg per day.
  • the appropriate dose may be administered in a single dose or as divided doses presented at appropriate intervals for example as two, three four or more subdoses per day.
  • inert, pharmaceutically acceptable carriers are used.
  • the pharmaceutical carrier can be either solid or liquid. Solid form preparations include, for example, powders, tablets, dispersible granules, capsules, cachets, and suppositories.
  • compositions generally are administered in an amount effective for treatment or prophylaxis of a specific condition or conditions. Initial dosing in a human is accompanied by clinical monitoring of symptoms, such symptoms being determined for the selected condition.
  • the compositions are administered in an amount of active agent of at least about 100 ⁇ g/kg body weight. In most cases they will be administered in one or more doses in an amount not in excess of about 20 mg/kg body weight per day. Preferably, in most cases, the dose is from about 100 ⁇ g/kg to about 5 mg/kg body weight, daily.
  • the daily dosage level of active agent will be 0.1 mg/kg to 10 mg/kg and typically around 1 mg/kg.
  • terapéuticaally effective amount is meant a symptom- alleviating or symptom -reducing amount, a cholesterol-reducing amount, a fatty acid absorption blocking amount, a protein and/or carbohydrate digestion-blocking amount and/or a de novo cholesterol biosynthesis-blocking amount of a compound according to the invention.
  • blocking means either total blockage or partial blockage.
  • FXR is proposed to be a bile acid sensor. As a result, it modulates both the synthetic output of bile acids in the liver and their recycling in the intestine, by regulating bile acid binding proteins.
  • the invention concerns a method for regulating bile transport in a mammal, in a preferred embodiment a human, which comprises activating the NR1 H4 receptor with a therapeutically effective amount of a compound according to the invention.
  • the invention further concerns a method of blocking fatty acid absorption in the intestine of a mammal comprising administering to the mammal a therapeutically effective amount of a compound according to the invention.
  • the invention may also be used to treat obesity in a mammal, particularly in humans.
  • Genes found to be regulated by GW 4064 are genes down-regulated in the liver, genes up-regulated in the liver and genes having altered expression in the intestine.
  • Genes that up-regulate in the liver include small heterodimer partner homolog (d86580); bile salt export pump, bsep (RefSeq NM 003742, XM 003644, and XM 033122); phospholipid transfer protein, PLTP (RefSeq NM 006227, XM 009490, XM 029929, and XM 029930); amithine palmitoyltransferase II, CPTII (RefSeq NM 000098, XM 001758, XM 038866, and XM 038867); phenylethanolamine-N-methyltransferase, PNMT (RefSeq NM 002686, XM 008597, andXM 049837); insulin-induced growth-response protein CL-6 (113619); elongation factor 2, EF-2 (y07504); mouse cornichon;
  • the TIF2 fragment was subsequently biotinylated by addition of 40-120 ⁇ l of a biotinamidocaproate N-hydroxysuccinimide-ester (Sigma) solution (20 mg/ml in DMSO). Overhead rotating samples were incubated for 2 hours at room temperature. Unincorporated label was then separated using G25 Gel filtration chromatography (Pharmacia Biotech, Sweden). Protein containing fractions from the column were pooled and tested for activity in the assay as described below.
  • a biotinamidocaproate N-hydroxysuccinimide-ester Sigma
  • the LANCE signal was detected by a Perkin Elmer VICTOR2VTM
  • Step 5 Preparation of a resin-bound thiourea (compound 7) [0099] A 0.2 M solution of Fmoc-NCS (5 eq) in anhydrous CH 2 CI 2 was added to a bottle containing the aminated Argogel-MB-HCO resin (resin compound 5). The bottle was placed on a shaker for one hour to form resin compound 6. The resin was washed with CH 2 CI 2 (3x) and DMF (3x) and subsequently reacted with 20 % piperidine in DMF (5 eq) for one hour to produce a resin-bound thiourea (resin compound 7). The resin was then washed with DMF (3x) and MeOH (3x) and used directly in the next step.
  • Step 1 Immobilization of a carboxylic acid (compound 11 ) on Bromo-Wang resin
  • Step 4 Cleavage of 2-aminothiazole to form products 10 from resin.
  • Luciferase reporter activity was measured in triplicates from extracts of cells after incubating cells in culture medium (DMEM [Gibco-BRL] + 10% FCS [PAA laboratories]) for 16 hours (5% C0 2 , 37°C) containing 0.5% DMSO (control) or 0.5% DMSO with increasing concentrations of compounds.
  • Examples of such dose response assays in the HEK293-FXR cell line are shown in Fig. 5A for LN6348, in Fig 5B for LN6316, in Fig.5C for LN6365 and in Fig. 5D for LN6322.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des composés de formule générale (I) qui se lient au récepteur NR1H4 et agissent comme agonistes dudit récepteur. L'invention concerne également le traitement de maladies et/ou d'états pathologiques par le biais de la liaison de ces composés au récepteur nucléaire, ainsi que la production de médicaments faisant appel à ces composés.
EP02750474A 2001-08-13 2002-08-13 Composes de liaison au recepteur nucleaire nr1h4 Ceased EP1423113A4 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02750474A EP1423113A4 (fr) 2001-08-13 2002-08-13 Composes de liaison au recepteur nucleaire nr1h4

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP01119473 2001-08-13
EP01119473A EP1285914B1 (fr) 2001-08-13 2001-08-13 Ligands du récepteur nucéaire nr1h4
US10/185,731 US6974830B2 (en) 2001-08-13 2002-07-01 NR1H4 nuclear receptor binding compounds
US185731 2002-07-01
EP02750474A EP1423113A4 (fr) 2001-08-13 2002-08-13 Composes de liaison au recepteur nucleaire nr1h4
PCT/US2002/025438 WO2003015777A1 (fr) 2001-08-13 2002-08-13 Composes de liaison au recepteur nucleaire nr1h4

Publications (2)

Publication Number Publication Date
EP1423113A1 true EP1423113A1 (fr) 2004-06-02
EP1423113A4 EP1423113A4 (fr) 2007-04-18

Family

ID=26076685

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02750474A Ceased EP1423113A4 (fr) 2001-08-13 2002-08-13 Composes de liaison au recepteur nucleaire nr1h4

Country Status (2)

Country Link
EP (1) EP1423113A4 (fr)
WO (1) WO2003015777A1 (fr)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7138390B2 (en) 2001-03-12 2006-11-21 Intercept Pharmaceuticals Steroids as agonists for FXR
US6987121B2 (en) 2002-04-25 2006-01-17 Smithkline Beecham Corporation Compositions and methods for hepatoprotection and treatment of cholestasis
GB0315111D0 (en) 2003-06-27 2003-07-30 Cancer Rec Tech Ltd Substituted 5-membered ring compounds and their use
PL1700856T3 (pl) 2003-12-26 2016-05-31 Kyowa Hakko Kirin Co Ltd Pochodna tiazolu
US10987362B2 (en) 2004-03-12 2021-04-27 Intercept Pharmaceuticals, Inc. Treatment of fibrosis using FXR ligands
PT1734970E (pt) 2004-03-12 2015-03-11 Intercept Pharmaceuticals Inc Tratamento de fibrose utilizando ligandos de rfx
WO2006012642A2 (fr) 2004-07-30 2006-02-02 Exelixis, Inc. Derives de pyrrole en tant qu'agents pharmaceutiques
WO2006028970A1 (fr) 2004-09-02 2006-03-16 Cengent Therapeutics, Inc. Derives d'inhibiteurs de thiazole et de thiadiazole de tyrosine phosphatases
WO2006029719A2 (fr) * 2004-09-14 2006-03-23 Bayer Healthcare Ag Diagnostics et traitements de maladies associees a la sous-famille 1, du groupe h, membre 4 de recepteur nucleaire (nr1h4)
ITMI20050912A1 (it) 2005-05-19 2006-11-20 Erregierre Spa Processo di preparazione di acidi 3-a-ya(b)-diidrossi-6-a(b)-alchil-5b-colanici
CA2928178C (fr) 2007-01-19 2019-09-10 Intercept Pharmaceuticals, Inc. Modulateurs de tgr5 et leurs procedes d'utilisation
EA020310B1 (ru) 2008-07-30 2014-10-30 Интерсепт Фармасьютикалз, Инк. Модуляторы рецептора tgr5 и их применение
AU2009316566B9 (en) 2008-11-19 2014-05-15 Intercept Pharmaceuticals, Inc. TGR5 modulators and method of use thereof
US20110257139A1 (en) 2008-12-19 2011-10-20 Royal College Of Surgeons In Ireland Treatment of diarrhoea
EP2545964A1 (fr) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Nouveaux composés se liant au fxr (nr1 h4) et modulant son activité
US9982008B2 (en) 2012-06-19 2018-05-29 Intercept Pharmaceuticals, Inc. Preparation and uses of obeticholic acid
ES2822375T3 (es) 2012-06-19 2021-04-30 Intercept Pharmaceuticals Inc Preparación de la forma no cristalina del ácido obeticólico
CA3252823A1 (en) 2016-06-13 2025-02-25 Gilead Sciences Inc Fxr (nr1h4) modulating compounds
SI3730487T1 (sl) 2016-06-13 2022-08-31 Gilead Sciences, Inc. Azetidinski derivati kot modulatorji FXR (NR1H4)
JP6906626B2 (ja) 2017-03-28 2021-07-21 ギリアード サイエンシーズ， インコーポレイテッド 肝疾患を処置するための治療的組み合わせ
US11225473B2 (en) 2019-01-15 2022-01-18 Gilead Sciences, Inc. FXR (NR1H4) modulating compounds
EP3927683A1 (fr) 2019-02-19 2021-12-29 Gilead Sciences, Inc. Formes solides d'agonistes de fxr
WO2020249064A1 (fr) * 2019-06-14 2020-12-17 Nanjing Ruijie Pharma Co., Ltd. Composés pour la modulation de fxr
WO2021009332A1 (fr) 2019-07-18 2021-01-21 Enyo Pharma Procédé pour diminuer les effets secondaires de l'interféron
CA3159163A1 (fr) 2020-01-15 2021-07-22 Raphael Darteil Utilisation d'agonistes de fxr pour traiter une infection par le virus de l'hepatite d
US11478533B2 (en) 2020-04-27 2022-10-25 Novo Nordisk A/S Semaglutide for use in medicine
CA3204800A1 (fr) 2021-01-14 2022-07-21 Raphael Darteil Effet synergique d'un agoniste de fxr et d'ifn pour le traitement d'une infection par le virus de l'hepatite b
US20240216364A1 (en) 2021-04-28 2024-07-04 Enyo Pharma Strong potentiation of tlr3 agonists effects using fxr agonists as a combined treatment

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK150068C (da) * 1978-06-02 1987-06-29 Pfizer Analogifremgangsmaade til fremstilling af aminothiazoler
JPH04173782A (ja) * 1990-11-08 1992-06-22 Taisho Pharmaceut Co Ltd ２―スルホンアミド―４，５―ジフェニルチアゾール誘導体
WO1992015570A1 (fr) * 1991-03-07 1992-09-17 Hisamitsu Pharmaceutical Co., Inc. Nouveau derive de diphenylthiazole
FR2692893B1 (fr) * 1992-06-24 1994-09-02 Sanofi Elf Dérivés alkylamino ramifiés du thiazole, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent.
JPH07149745A (ja) * 1993-11-30 1995-06-13 Hisamitsu Pharmaceut Co Inc 新規な２−アミノチアゾール誘導体
FR2714059B1 (fr) * 1993-12-21 1996-03-08 Sanofi Elf Dérivés amino ramifiés du thiazole, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent.
KR980700077A (ko) * 1994-11-29 1998-03-30 나까토미 히로타카 2-아미노티아졸유도체 및 그 염류로 이루어진 항균제 또는 살균제(Antibacterial Prepartion or Bactericide comprising 2-Aminothiazole Derivative or Salt Thereof
FR2735777B1 (fr) * 1995-06-21 1997-09-12 Sanofi Sa Derives de 4-phenylaminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant
JP4136024B2 (ja) * 1995-12-29 2008-08-20 富山化学工業株式会社 ２−アミノチアゾ−ル誘導体またはその塩
FR2796380B3 (fr) * 1999-07-15 2001-08-17 Sanofi Synthelabo Nouveaux derives d'aminothiazoles, leur preparation et les compositions pharmaceutiques les contenant

Also Published As

Publication number Publication date
WO2003015777A1 (fr) 2003-02-27
EP1423113A4 (fr) 2007-04-18

Similar Documents

Publication Publication Date Title
US6974830B2 (en) NR1H4 nuclear receptor binding compounds
WO2003015777A1 (fr) Composes de liaison au recepteur nucleaire nr1h4
US20070010562A1 (en) Nr1h4 nuclear receptor binding compounds
EP1407774A1 (fr) 2-amino-4-quinazolinones se liant au récepteur nucléair LXR
US6699879B1 (en) Phenyl urea and phenyl thiourea derivatives as orexin receptor antagonists
US6545009B1 (en) Retinoid-related receptor function regulating agent
KR101120916B1 (ko) 페닐아세트아미드 및 글루코키나제 조절제로서의 이의 용도
US20060148876A1 (en) Nr3b1 nuclear receptor binding 3-substituted pyrazoles
EP1398032A1 (fr) 4-oxoquinazolines se liant au récepteur nucléair LXR
US20050203151A1 (en) Novel compounds, compositions and uses thereof for treatment of metabolic disorders and related conditions
US20040063775A1 (en) Five-membered heterocyclic alkanoic acid derivative
CZ20021903A3 (cs) Substituované deriváty oxazolu a thiazolu jakoľto HPPAR-alfa aktivátory
SK288236B6 (sk) Chinolinylfenylsulfónamidová zlúčenina, jej použitie ako liečivo a farmaceutické prípravky obsahujúce túto zlúčeninu
CA2382581C (fr) Derives de benzylthiazolidine-2,4-dione substitues
JP2005528384A (ja) 増殖性細胞においてアポトーシスを誘導するための化合物および方法
WO2003053976A1 (fr) Derives de pyrazolo[1,5-a] pyrimidine utilises comme modulateurs de ppar
EP1940815B1 (fr) Sels de modulateurs de ppar et procedes de traitement de troubles metaboliques
JP2002348281A (ja) ５員複素環アルカン酸誘導体
KR102101235B1 (ko) 신규 sirt 1 활성화제 및 이의 의학적 용도
HK1036972A (en) Retinoid-associated receptor regulators

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040225

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

RIN1 Information on inventor provided before grant (corrected)

Inventor name: SUD, MANISH

Inventor name: SAGE, CARLTON

Inventor name: OTTE, KERSTIN

Inventor name: LEE, MATTHEW

Inventor name: KREMOSER, CLAUS

Inventor name: KRANZ, HARALD

Inventor name: KOGL, MANFRED

Inventor name: KOBER, INGO

Inventor name: KIELY, JOHN

Inventor name: HEBERT, NORMAND

Inventor name: HANECAK, RONNIE

Inventor name: GIEGRICH, KRISTINA

Inventor name: GAHMAN, TIM

Inventor name: DNEPROVSKAIA, ELENA

Inventor name: DEUSCHLE, ULRICH

Inventor name: CHERUVALLATH, ZACH

Inventor name: BAUER, ULRIKE

RIN1 Information on inventor provided before grant (corrected)

Inventor name: SUD, MANISH

Inventor name: SAGE, CARLTON

Inventor name: OTTE, KERSTIN

Inventor name: LEE, MATTHEW

Inventor name: KREMOSER, CLAUS

Inventor name: KRANZ, HARALD

Inventor name: KOGL, MANFRED

Inventor name: KOBER, INGO

Inventor name: KIELY, JOHN

Inventor name: HEBERT, NORMAND

Inventor name: HANECAK, RONNIE

Inventor name: GIEGRICH, KRISTINA

Inventor name: GAHMAN, TIM

Inventor name: DNEPROVSKAIA, ELENA

Inventor name: DEUSCHLE, ULRICH

Inventor name: CHERUVALLATH, ZACH

Inventor name: BAUER, ULRIKE

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: PHENEX PHARMACEUTICALS AG

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: PHENEX PHARMACEUTICALS AG

A4 Supplementary search report drawn up and despatched

Effective date: 20070315

RIC1 Information provided on ipc code assigned before grant

Ipc: C07D 277/52 20060101ALI20070309BHEP

Ipc: C07D 277/46 20060101ALI20070309BHEP

Ipc: C07D 277/44 20060101ALI20070309BHEP

Ipc: C07D 277/42 20060101ALI20070309BHEP

Ipc: C07D 277/40 20060101ALI20070309BHEP

Ipc: A61K 31/426 20060101AFI20030306BHEP

17Q First examination report despatched

Effective date: 20080602

RIN1 Information on inventor provided before grant (corrected)

Inventor name: SUD, MANISH

Inventor name: DNEPROVSKAIA, ELENAC

Inventor name: DEUSCHLE, ULRICH

Inventor name: CHERUVALLATH, ZACH

Inventor name: SAGE, CARLTON

Inventor name: OTTE, KERSTIN

Inventor name: LEE, MATTHEW

Inventor name: KREMOSER, CLAUS

Inventor name: KRANZ, HARALD

Inventor name: KOGL, MANFRED

Inventor name: KOBER, INGO

Inventor name: KIELY, JOHN

Inventor name: HEBERT, NORMANDC

Inventor name: HANECAK, RONNIE

Inventor name: GIEGRICH, KRISTINA

Inventor name: GAHMAN, TIM

Inventor name: BAUER, ULRIKE

REG Reference to a national code

Ref country code: DE

Ref legal event code: R003

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20110331