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WO2005118580A3 - Tricyclic compounds as inhibitors of the hypoxic signaling pathway - Google Patents

Tricyclic compounds as inhibitors of the hypoxic signaling pathway 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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WO
WIPO (PCT)
Prior art keywords
tricyclic compounds
inhibitors
signaling pathway
activity
hypoxic signaling
Prior art date
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Ceased
Application number
PCT/US2005/016569
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French (fr)
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WO2005118580A2 (en
Inventor
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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US Department of Health and Human Services
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US Department of Health and Human Services
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Application filed by US Department of Health and Human Services filed Critical US Department of Health and Human Services
Publication of WO2005118580A2 publication Critical patent/WO2005118580A2/en
Publication of WO2005118580A3 publication Critical patent/WO2005118580A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/24—[b,e]-condensed with two six-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/39—Heterocyclic compounds having sulfur as a ring hetero atom having oxygen in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic 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
    • C07D215/12—Heterocyclic 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
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic 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
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • C07D219/12—Amino-alkylamino radicals attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/46—Phenazines
    • C07D241/48—Phenazines with hydrocarbon radicals, substituted by nitrogen atoms, directly attached to the ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/38—[b, e]-condensed with two six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
    • C07D327/06—Six-membered rings
    • C07D327/08—[b,e]-condensed with two six-membered carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/08—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

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

Abstract

Tricyclic compounds that selectively inhibit HIF-lα activity are disclosed. Methods also are disclosed for reducing HIF-1α activity, and for inhibiting angiogenesis, tumorigenesis and/or metastasis, in a subject. In some embodiments, the tricyclic compounds surprisingly inhibit HIF-lα activity at non-cytotoxic concentrations, thereby avoiding drug side effects associated with significant cytotoxicity.
PCT/US2005/016569 2004-05-12 2005-05-11 Tricyclic compounds as inhibitors of the hypoxic signaling pathway Ceased WO2005118580A2 (en)

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 (en) 2005-12-15
WO2005118580A3 true WO2005118580A3 (en) 2006-08-03

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PCT/US2005/016569 Ceased WO2005118580A2 (en) 2004-05-12 2005-05-11 Tricyclic compounds as inhibitors of the hypoxic signaling pathway

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FR2904317A1 (en) 2006-07-27 2008-02-01 Inst Nat Sante Rech Med ANALOGUES OF HALOGENOBENZAMIDES BRANDED AS RADIOPHARMACEUTICALS
WO2009043093A1 (en) * 2007-10-04 2009-04-09 Newsouth Innovations Pty Limited Hif inhibition
EP2085390A1 (en) 2008-01-31 2009-08-05 Institut National De La Sante Et De La Recherche Medicale (Inserm) Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors
WO2010018458A2 (en) * 2008-08-12 2010-02-18 Crystalgenomics, Inc. Phenol derivatives and methods of use thereof
WO2010075869A1 (en) * 2008-12-30 2010-07-08 European Molecular Biology Laboratory (Embl) Toluidine sulfonamides and their use
CA2765044A1 (en) 2009-06-09 2010-12-16 California Capital Equity, Llc Benzyl substituted triazine derivatives and their therapeutical applications
CN102573480B (en) 2009-06-09 2015-06-10 加利福尼亚资本权益有限责任公司 Triazine derivatives and their therapeutic applications
CN102573473B (en) 2009-06-09 2015-05-27 加利福尼亚资本权益有限责任公司 Isoquinoline, quinoline, and quinazoline derivatives as inhibitors of HEDGEHOG signaling
SI2624695T1 (en) 2010-10-08 2016-01-29 Nivalis Therapeutics, Inc. Novel substituted quinoline compounds as s-nitrosoglutathione reductase inhibitors
WO2012083165A1 (en) 2010-12-16 2012-06-21 N30 Pharmaceuticals, Llc Novel substituted bicyclic aromatic compounds as s-nitrosoglutathione reductase inhibitors
WO2016130501A1 (en) 2015-02-09 2016-08-18 Incyte Corporation Aza-heteroaryl compounds as pi3k-gamma inhibitors
WO2017044766A1 (en) 2015-09-10 2017-03-16 Nivalis Therapeutics, Inc. Solid forms of an s-nitrosoglutathione reductase inhibitor
SI3371190T1 (en) 2015-11-06 2022-08-31 Incyte Corporation Heterocyclic compounds as pi3k-gamma inhibitors
WO2017120194A1 (en) 2016-01-05 2017-07-13 Incyte Corporation Pyridine and pyridimine compounds as pi3k-gamma inhibitors
WO2017223414A1 (en) 2016-06-24 2017-12-28 Incyte Corporation HETEROCYCLIC COMPOUNDS AS PI3K-γ INHIBITORS
SI3697789T1 (en) 2017-10-18 2022-04-29 Incyte Corporation Condensed imidazole derivatives substituted by tertiary hydroxy groups as pi3k-gamma inhibitors
CR20250050A (en) 2018-09-05 2025-03-19 Incyte Corp Crystalline forms of a phosphoinositide 3-kinase (pi3k) inhibitor
RS65335B1 (en) 2018-10-05 2024-04-30 Annapurna Bio Inc Compounds and compositions for treating conditions associated with apj receptor activity
JP7581236B2 (en) 2019-04-18 2024-11-12 ニカン セラピューティクス，インコーポレイテッド Tetrahydro-1H-cyclopenta[cd]indene derivatives as hypoxia-inducible factor 2(alpha) inhibitors
WO2021158495A1 (en) * 2020-02-03 2021-08-12 Bristol-Myers Squibb Company Benzo[5,6][1,4]dioxino[2,3-b]pyridine compounds useful as irak4 inhibitors

Citations (4)

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Patent Citations (4)

* Cited by examiner, † Cited by third party
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EP0098098A2 (en) * 1982-06-25 1984-01-11 Development Finance Corporation Of New Zealand Acridinecarboxamide compounds
EP0172744A2 (en) * 1984-08-16 1986-02-26 Development Finance Corporation Of New Zealand Phenazinecarboxamide compounds
EP0206802A2 (en) * 1985-06-24 1986-12-30 Cancer Research Campaign Technology Limited Substituted quinoline derivatives
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