WO2005118580A3 - Composes tricycliques utiles comme inhibiteurs du mecanisme de signalisation hypoxique - Google Patents

Composes tricycliques utiles comme inhibiteurs du mecanisme de signalisation hypoxique Download PDF

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Publication number
WO2005118580A3
WO2005118580A3 PCT/US2005/016569 US2005016569W WO2005118580A3 WO 2005118580 A3 WO2005118580 A3 WO 2005118580A3 US 2005016569 W US2005016569 W US 2005016569W WO 2005118580 A3 WO2005118580 A3 WO 2005118580A3
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WIPO (PCT)
Prior art keywords
tricyclic compounds
inhibitors
signaling pathway
activity
hypoxic signaling
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PCT/US2005/016569
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English (en)
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WO2005118580A2 (fr
Inventor
Giovanni Melillo
Robert H Shoemaker
John H Cardellina
Michael J Currens
Mark Creighton-Gutteridge
Badarch Uranchimeg
Annamaria Rapisarda
Dominic A Scudiero
Original Assignee
Us Gov Health & Human Serv
Giovanni Melillo
Robert H Shoemaker
John H Cardellina
Michael J Currens
Mark Creighton-Gutteridge
Badarch Uranchimeg
Annamaria Rapisarda
Dominic A Scudiero
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Application filed by Us Gov Health & Human Serv, Giovanni Melillo, Robert H Shoemaker, John H Cardellina, Michael J Currens, Mark Creighton-Gutteridge, Badarch Uranchimeg, Annamaria Rapisarda, Dominic A Scudiero filed Critical Us Gov Health & Human Serv
Publication of WO2005118580A2 publication Critical patent/WO2005118580A2/fr
Publication of WO2005118580A3 publication Critical patent/WO2005118580A3/fr

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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D319/00Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/101,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/141,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/24[b,e]-condensed with two six-membered rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/38Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/38Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/39Heterocyclic compounds having sulfur as a ring hetero atom having oxygen in the same ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/473Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/5381,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14Radicals substituted by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D219/00Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 ring system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D219/00Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 ring system
    • C07D219/08Nitrogen atoms
    • C07D219/10Nitrogen atoms attached in position 9
    • C07D219/12Amino-alkylamino radicals attached in position 9
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38Heterocyclic 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
    • C07D241/46Phenazines
    • C07D241/48Phenazines with hydrocarbon radicals, substituted by nitrogen atoms, directly attached to the ring nitrogen atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/341,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/38[b, e]-condensed with two six-membered rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D279/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/101,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/141,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/36[b, e]-condensed, at least one with a further condensed benzene ring
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    • C07D327/00Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
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    • C07D339/00Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention porte sur des composés tricycliques qui inhibent sélectivement l'activité de HIF-l?. L'invention porte également sur des méthodes visant à réduire l'activité de HIF-1? et inhiber l'angiogenèse, la tumorigenèse et/ou la métastase chez un sujet. Selon certains modes de mise en oeuvre, les composés tricycliques inhibent curieusement l'activité de HIF-l? à des concentrations non cytotoxiques, ce qui évite les effets secondaires des médicaments associés à une cytotoxicité importante.
PCT/US2005/016569 2004-05-12 2005-05-11 Composes tricycliques utiles comme inhibiteurs du mecanisme de signalisation hypoxique WO2005118580A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US57061504P 2004-05-12 2004-05-12
US60/570,615 2004-05-12
US61827904P 2004-10-12 2004-10-12
US60/618,279 2004-10-12

Publications (2)

Publication Number Publication Date
WO2005118580A2 WO2005118580A2 (fr) 2005-12-15
WO2005118580A3 true WO2005118580A3 (fr) 2006-08-03

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FR2904317A1 (fr) 2006-07-27 2008-02-01 Inst Nat Sante Rech Med Analogues d'halogenobenzamides marques a titre de radiopharmaceutiques
WO2009043093A1 (fr) * 2007-10-04 2009-04-09 Newsouth Innovations Pty Limited Inhibition de hif
EP2085390A1 (fr) 2008-01-31 2009-08-05 Institut National De La Sante Et De La Recherche Medicale (Inserm) Analogues d'halobenzamide marqués en tant que produits radiopharmaceutiques multimodaux et leurs précurseurs
WO2010018458A2 (fr) * 2008-08-12 2010-02-18 Crystalgenomics, Inc. Dérivés de phénol et leurs procédés d'utilisation
WO2010075869A1 (fr) * 2008-12-30 2010-07-08 European Molecular Biology Laboratory (Embl) Toluidine sulfonamides et leur utilisation
EP2440048B8 (fr) 2009-06-09 2015-12-16 NantBioScience, Inc. Dérivés de l'isoquinoléine, de la quinoléine et de la quinazoléine servant d'inhibiteurs de signal hedgehog
BRPI1011319A2 (pt) 2009-06-09 2016-06-21 California Capital Equity Llc derivados de triazina benzil-substituídos e suas aplicações terapêuticas
BRPI1011318A2 (pt) 2009-06-09 2019-09-24 California Capital Equity Llc derivados de triazina e suas aplicações terapêuticas
EP2977050A1 (fr) 2010-10-08 2016-01-27 Nivalis Therapeutics, Inc. Nouveaux composés quinoléine substitués comme inhibiteurs de la s-nitrosoglutathione réductase
US8785643B2 (en) 2010-12-16 2014-07-22 N30 Pharmaceuticals, Inc. Substituted bicyclic aromatic compounds as S-nitrosoglutathione reductase inhibitors
US9586949B2 (en) 2015-02-09 2017-03-07 Incyte Corporation Aza-heteroaryl compounds as PI3K-gamma inhibitors
US10399946B2 (en) 2015-09-10 2019-09-03 Laurel Therapeutics Ltd. Solid forms of an S-Nitrosoglutathione reductase inhibitor
HUE059324T2 (hu) 2015-11-06 2022-11-28 Incyte Corp Heterociklusos vegyületek, mint PI3K-gamma inhibitorok
AR107293A1 (es) 2016-01-05 2018-04-18 Incyte Corp COMPUESTOS DE PIRIDINA Y PIRIDIMINA COMO INHIBIDORES DE PI3K-g
AR108875A1 (es) 2016-06-24 2018-10-03 Incyte Corp COMPUESTOS HETEROCÍCLICOS COMO INHIBIDORES DE PI3K-g
IL295978B1 (en) 2017-10-18 2023-09-01 Incyte Corp Concentrated imidazole derivatives substituted by tertiary hydroxy groups as P13K-gamma inhibitors
US11186580B2 (en) 2018-09-05 2021-11-30 Incyte Corporation Crystalline forms of a phosphoinositide 3-kinase (PI3K) inhibitor
EP4364798A2 (fr) 2018-10-05 2024-05-08 Annapurna Bio Inc. Composés et compositions pour le traitement d'états associés à l'activité du récepteur apj
WO2021158495A1 (fr) * 2020-02-03 2021-08-12 Bristol-Myers Squibb Company Composés de benzo[5,6] [1,4]dioxino[2,3-b]pyridine utiles en tant qu'inhibiteurs de l'irak4

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Patent Citations (4)

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EP0172744A2 (fr) * 1984-08-16 1986-02-26 Development Finance Corporation Of New Zealand Composés de phénazinecarboxamide
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