CA2538759C - Substituted heterocyclic compounds as sirtuin inhitibitors - Google Patents

Substituted heterocyclic compounds as sirtuin inhitibitors Download PDF

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Publication number
CA2538759C
CA2538759C CA2538759A CA2538759A CA2538759C CA 2538759 C CA2538759 C CA 2538759C CA 2538759 A CA2538759 A CA 2538759A CA 2538759 A CA2538759 A CA 2538759A CA 2538759 C CA2538759 C CA 2538759C
Authority
CA
Canada
Prior art keywords
compound
disease
protein
sirt1
disorder
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.)
Expired - Lifetime
Application number
CA2538759A
Other languages
English (en)
French (fr)
Other versions
CA2538759A1 (en
Inventor
Andrew Napper
Peter Distefano
Jeffrey Hixon
Thomas Mcdonagh
Jonathan M. Solomon
L. Julie Huber
Rory Curtis
Russell J. Thomas
Jean-Francois Pons
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.)
AOP Orphan IP AG
Original Assignee
Elixir Pharmaceuticals Inc
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
Application filed by Elixir Pharmaceuticals Inc filed Critical Elixir Pharmaceuticals Inc
Publication of CA2538759A1 publication Critical patent/CA2538759A1/en
Application granted granted Critical
Publication of CA2538759C publication Critical patent/CA2538759C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • 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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/88—Carbazoles; Hydrogenated carbazoles 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Endocrinology (AREA)
  • Psychology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CA2538759A 2003-09-12 2004-09-13 Substituted heterocyclic compounds as sirtuin inhitibitors Expired - Lifetime CA2538759C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US50281103P 2003-09-12 2003-09-12
US60/502,811 2003-09-12
US53144303P 2003-12-19 2003-12-19
US60/531,443 2003-12-19
US56050904P 2004-04-07 2004-04-07
US60/560,509 2004-04-07
PCT/US2004/029942 WO2005026112A2 (en) 2003-09-12 2004-09-13 Methods of treating a disorder

Publications (2)

Publication Number Publication Date
CA2538759A1 CA2538759A1 (en) 2005-03-24
CA2538759C true CA2538759C (en) 2015-11-03

Family

ID=34317479

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2538759A Expired - Lifetime CA2538759C (en) 2003-09-12 2004-09-13 Substituted heterocyclic compounds as sirtuin inhitibitors

Country Status (6)

Country Link
US (1) US20050209300A1 (enExample)
EP (1) EP1677794B1 (enExample)
JP (1) JP4908215B2 (enExample)
CA (1) CA2538759C (enExample)
ES (1) ES2530972T3 (enExample)
WO (1) WO2005026112A2 (enExample)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7977049B2 (en) 2002-08-09 2011-07-12 President And Fellows Of Harvard College Methods and compositions for extending the life span and increasing the stress resistance of cells and organisms
US20050096256A1 (en) 2003-07-01 2005-05-05 President And Fellows Of Harvard College Compositions for manipulating the lifespan and stress response of cells and organisms
US20070105109A1 (en) * 2003-07-02 2007-05-10 Geesaman Bard J Sirt1 and genetic disorders
US20060074124A1 (en) 2003-09-12 2006-04-06 Andrew Napper Methods of treating a disorder
TW200526668A (en) * 2003-10-02 2005-08-16 Salmedix Inc Substituted indole derivatives
EP1694323A4 (en) * 2003-12-19 2009-05-13 Elixir Pharmaceuticals Inc METHOD FOR TREATING A DISEASE
EP1708689A2 (en) 2003-12-29 2006-10-11 The President and Fellows of Harvard College Compositions for treating or preventing obesity and insulin resistance disorders
US8017634B2 (en) 2003-12-29 2011-09-13 President And Fellows Of Harvard College Compositions for treating obesity and insulin resistance disorders
EP1817025A2 (en) 2004-11-23 2007-08-15 PTC Therapeutics, Inc. Tetrahydrocarbazoles as active agents for inhibiting vegf production by translational control
GB2422828A (en) * 2005-02-03 2006-08-09 Hunter Fleming Ltd Tricyclic cytoprotective compounds comprising an indole residue
US7998974B2 (en) 2005-03-03 2011-08-16 Sirtris Pharmaceuticals, Inc. Fused heterocyclic compounds and their use as sirtuin modulators
WO2006138418A2 (en) 2005-06-14 2006-12-28 President And Fellows Of Harvard College Improvement of cognitive performance with sirtuin activators
US20090022694A1 (en) * 2005-10-18 2009-01-22 Distefano Peter Sirt1 inhibition
WO2008019825A1 (en) * 2006-08-14 2008-02-21 Santhera Pharmaceuticals (Schweiz) Ag Use of tricyclic indole derivatives for the treatment of muscular diseases
EP1891949A1 (en) * 2006-08-14 2008-02-27 Santhera Pharmaceuticals (Schweiz) AG Use of tricyclic indole derivatives for the treatment of muscular atrophy
US20110009474A1 (en) * 2007-04-12 2011-01-13 President And Fellows Of Harvard College Sirtuin based methods and compositions for treating beta-catenin-related conditions
WO2009099643A1 (en) * 2008-02-07 2009-08-13 The J. David Gladstone Institutes Use of sirt1 activators or inhibitors to modulate an immune response
EP2367563A4 (en) 2008-12-08 2012-12-19 Univ Northwestern PROCESS FOR HSF-1 MODULATION
WO2012142256A2 (en) * 2011-04-12 2012-10-18 The Regents Of The University Of California Modulators of mitochondrial protein import
AR088377A1 (es) 2011-10-20 2014-05-28 Siena Biotech Spa Proceso para la preparacion de 6-cloro-2,3,4,9-tetrahidro-1h-carbazol-1-carboxamida y compuestos intermedios de esta
AU2015315174B2 (en) * 2014-09-10 2019-12-12 Epizyme, Inc. Smyd inhibitors
CA2968884A1 (en) 2014-12-10 2016-06-16 Massachusetts Institute Of Technology Fused 1,3-azole derivatives useful for the treatment of proliferative diseases
RU2018132559A (ru) 2016-02-16 2020-03-17 Массачусетс Инститьют Оф Текнолоджи Связывающие молекулы для max в качестве модуляторов myc и их применения
PY2438443A (es) 2023-05-16 2025-06-18 Aop Orphan Ip Ag Nuevos polimorfos de (s)-6-cloro-2,3,4,9-tetrahidro-1h-carbazol-1-carboxamida en forma cristalina
PY2438446A (es) 2023-05-16 2025-06-18 Aop Orphan Ip Ag Preparación de (s)-6-cloro-2,3,4,9- tetrahidro-1h-carbazol-1-carboxamida en forma enantioméricamente enriquecida mediante proceso de resolución

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3769298A (en) * 1971-04-02 1973-10-30 Pfizer Substituted aminomethylcarbazoles
BE793493A (fr) * 1971-12-30 1973-06-29 Hoffmann La Roche Composes tricycliques
DE2226703A1 (de) * 1972-05-25 1973-12-13 Schering Ag Neue tetrahydrocarbazolderivate und verfahren zu ihrer herstellung
US4009181A (en) * 1973-01-22 1977-02-22 Hoffmann-La Roche Inc. Cyclopenta[b]indole-2-carboxylic acids and derivatives thereof
DE2431292A1 (de) * 1974-06-27 1976-01-15 Schering Ag Neue carbazol-derivate
BG25793A3 (bg) * 1973-07-18 1978-12-12 Schering Aktiengesellschaft Метод за получаване на карбазолови деривати
MX9700696A (es) * 1994-07-27 1997-04-30 Sankyo Co Compuestos heterociclicos, utiles como productores de efecto aloesterico en receptores muscarinicos.
US6045398A (en) * 1995-07-10 2000-04-04 International Business Machines Corporation Battery accepting unit and battery pack
US5830911A (en) * 1996-08-14 1998-11-03 American Home Products Corporation Pyranoindole and tetrahydrocarbazole inhibitors of COX-2
WO2002102981A2 (en) * 2001-06-15 2002-12-27 The Trustees Of Columbia University In The City Of New York SIR2α-BASED THERAPEUTIC AND PROPHYLACTIC METHODS
JP2005518375A (ja) * 2001-12-14 2005-06-23 ツェンタリス ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｇタンパク質結合受容体（ｇｐｃｒ）のためのリガンドとしてのテトラヒドロカルバゾール誘導体
CA2473740A1 (en) * 2002-01-18 2003-07-31 David Solow-Cordero Methods of treating conditions associated with an edg receptor

Also Published As

Publication number Publication date
CA2538759A1 (en) 2005-03-24
JP4908215B2 (ja) 2012-04-04
EP1677794A2 (en) 2006-07-12
EP1677794B1 (en) 2014-12-03
WO2005026112A3 (en) 2005-11-24
ES2530972T3 (es) 2015-03-09
WO2005026112A2 (en) 2005-03-24
JP2007505148A (ja) 2007-03-08
US20050209300A1 (en) 2005-09-22
EP1677794A4 (en) 2010-05-19

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