DE60332137D1 - Cyclohexyl-sulphone als gamma-sekretase-inhibitoren - Google Patents

Cyclohexyl-sulphone als gamma-sekretase-inhibitoren

Info

Publication number
DE60332137D1
DE60332137D1 DE60332137T DE60332137T DE60332137D1 DE 60332137 D1 DE60332137 D1 DE 60332137D1 DE 60332137 T DE60332137 T DE 60332137T DE 60332137 T DE60332137 T DE 60332137T DE 60332137 D1 DE60332137 D1 DE 60332137D1
Authority
DE
Germany
Prior art keywords
gamma
sekretase
inhibitoren
sulphone
als
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
DE60332137T
Other languages
English (en)
Inventor
Ian Churcher
Timothy Harrison
Sonia Kerrad
Alan John Nadin
Andrew Pate Owens
Duncan Edward Shaw
Joanne Thomson
Susannah Williams
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.)
Organon Pharma UK Ltd
Original Assignee
Merck Sharp and Dohme Ltd
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 Merck Sharp and Dohme Ltd filed Critical Merck Sharp and Dohme Ltd
Application granted granted Critical
Publication of DE60332137D1 publication Critical patent/DE60332137D1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • 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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C317/30—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
    • C07D231/18—One oxygen or sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/42—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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
    • 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
    • C07D277/36—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom 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
    • C07D307/64—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/34—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
DE60332137T 2002-10-04 2003-09-25 Cyclohexyl-sulphone als gamma-sekretase-inhibitoren Expired - Lifetime DE60332137D1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0223038.1A GB0223038D0 (en) 2002-10-04 2002-10-04 Therapeutic compounds
PCT/GB2003/004196 WO2004031139A1 (en) 2002-10-04 2003-09-25 Cyclohexyl sulphones as gamma-secretase inhibitors

Publications (1)

Publication Number Publication Date
DE60332137D1 true DE60332137D1 (en) 2010-05-27

Family

ID=9945312

Family Applications (1)

Application Number Title Priority Date Filing Date
DE60332137T Expired - Lifetime DE60332137D1 (en) 2002-10-04 2003-09-25 Cyclohexyl-sulphone als gamma-sekretase-inhibitoren

Country Status (9)

Country Link
US (1) US6890956B2 (de)
EP (1) EP1551799B1 (de)
JP (1) JP4653486B2 (de)
AT (1) ATE464287T1 (de)
AU (1) AU2003269211C1 (de)
CA (1) CA2500969A1 (de)
DE (1) DE60332137D1 (de)
GB (1) GB0223038D0 (de)
WO (1) WO2004031139A1 (de)

Families Citing this family (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0108591D0 (en) 2001-04-05 2001-05-23 Merck Sharp & Dohme Therapeutic agents
GB0120347D0 (en) 2001-08-21 2001-10-17 Merck Sharp & Dohme Therapeutic agents
WO2003032994A2 (de) * 2001-10-17 2003-04-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg 5-substituierte 4-amino-2-phenylamino-pyrimidinderivate und ihre verwendung als beta-amyloid modulatoren
KR100927304B1 (ko) 2001-12-27 2009-11-18 다이이찌 세이야꾸 가부시기가이샤 β-아밀로이드 단백 생산·분비 저해제
GB0223039D0 (en) * 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
US7521481B2 (en) 2003-02-27 2009-04-21 Mclaurin Joanne Methods of preventing, treating and diagnosing disorders of protein aggregation
MXPA05013631A (es) 2003-06-30 2006-02-24 Daiichi Seiyaku Co Derivado heterociclico de metilsulfona.
GB0323258D0 (en) * 2003-10-04 2003-11-05 Merck Sharp & Dohme Therapeutic compounds
WO2006009655A1 (en) * 2004-06-16 2006-01-26 Wyeth Diphenylimidazopyrimidine and -imidazole amines as inhibitors of b-secretase
EP2264036A1 (de) * 2005-01-14 2010-12-22 Wyeth LLC (Formerly Known As Wyeth) Amino-Imidazolone als Beta-Sekretase-Hemmer
US8362075B2 (en) 2005-05-17 2013-01-29 Merck Sharp & Dohme Corp. Cyclohexyl sulphones for treatment of cancer
US20090215775A1 (en) * 2005-05-17 2009-08-27 Huw David Lewis Sulphonamido-Substituted Cyclohexyl Sulphones for Treatment of Cancer
GB0513747D0 (en) * 2005-07-06 2005-08-10 Merck Sharp & Dohme Therapeutic compounds
US8133857B2 (en) * 2006-03-07 2012-03-13 The Brigham and Women's FHospital, Inc. NOTCH inhibition in the treatment of atherosclerosis
US9567396B2 (en) 2006-03-07 2017-02-14 Evonik Degussa Gmbh Notch inhibition in the prevention of vein graft failure
EP2089383B1 (de) 2006-11-09 2015-09-16 Probiodrug AG 3-hydroxy-1,5-dihydropyrrol-2-one derivate als inhibitoren von glutaminylcyclase zur behandlung von geschwüren, krebs und anderen krankheiten
CA2669693C (en) 2006-11-15 2018-06-12 Massachusetts Eye & Ear Infirmary Generation of inner ear cells
US9126987B2 (en) 2006-11-30 2015-09-08 Probiodrug Ag Inhibitors of glutaminyl cyclase
WO2008099210A2 (en) 2007-02-12 2008-08-21 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
AU2008220785B2 (en) 2007-03-01 2013-02-21 Vivoryon Therapeutics N.V. New use of glutaminyl cyclase inhibitors
US9656991B2 (en) 2007-04-18 2017-05-23 Probiodrug Ag Inhibitors of glutaminyl cyclase
WO2009035522A1 (en) * 2007-09-14 2009-03-19 Albert Einstein College Of Medicine Of Yeshiva University Use of gamma secretase inhibitors and notch pathway inhibitors for treatment and prevention of renal disease
US8461389B2 (en) 2008-04-18 2013-06-11 University College Dublin, National University Of Ireland, Dublin Psycho-pharmaceuticals
EP2273877B1 (de) * 2008-04-23 2014-04-16 Merck Sharp & Dohme Corp. Cyclobutylsulfone als notch-schonende gammasekretasehemmer
US10143711B2 (en) 2008-11-24 2018-12-04 Massachusetts Eye & Ear Infirmary Pathways to generate hair cells
WO2010090954A1 (en) * 2009-02-06 2010-08-12 Merck Sharp & Dohme Corp. Novel trifluoromethylsulfonamide gamma secretase inhibitor
WO2010114780A1 (en) 2009-04-01 2010-10-07 Merck Sharp & Dohme Corp. Inhibitors of akt activity
US20120129189A1 (en) * 2009-07-17 2012-05-24 Chulan Kwon Methods of Controlling Cell Proliferation
PL2475428T3 (pl) 2009-09-11 2015-12-31 Probiodrug Ag Pochodne heterocykliczne jako inhibitory cyklazy glutaminowej
EP2477963A4 (de) * 2009-09-18 2013-02-27 Zalicus Pharmaceuticals Ltd Arylsulfonderivate als calciumkanalblocker
MX2012004377A (es) 2009-10-14 2012-06-01 Merck Sharp & Dohme Piperidinas sustituidas que aumentan la actividad de p53 y sus usos.
EP2493497A4 (de) 2009-11-01 2013-07-24 Brigham & Womens Hospital Notch-hemmung bei der behandlung und prophylaxe von adipositas und dem stoffwechselsyndrom
US9181233B2 (en) 2010-03-03 2015-11-10 Probiodrug Ag Inhibitors of glutaminyl cyclase
DK2545047T3 (da) 2010-03-10 2014-07-28 Probiodrug Ag Heterocycliske inhibitorer af glutaminylcyclase (QC, EC 2.3.2.5)
WO2011131748A2 (en) 2010-04-21 2011-10-27 Probiodrug Ag Novel inhibitors
EP2584903B1 (de) 2010-06-24 2018-10-24 Merck Sharp & Dohme Corp. Neue heterozyklische verbindungen als erk-hemmer
EP2601293B1 (de) 2010-08-02 2017-12-06 Sirna Therapeutics, Inc. Rna-interferenz-vermittelte hemmung der catenin (cadherin-assoziiertes protein)-beta-1 (ctnnb1)- genexpression mittels kurzer interferierender nukleinsäuren (sina)
AU2011292261B2 (en) 2010-08-17 2015-05-14 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Hepatitis B virus (HBV) gene expression using short interfering nucleic acid (siNA)
EP2613782B1 (de) 2010-09-01 2016-11-02 Merck Sharp & Dohme Corp. Indazolderivate als erk-hemmer
EP2615916B1 (de) 2010-09-16 2017-01-04 Merck Sharp & Dohme Corp. Kondensierte pyrazolderivate als neue erk-hemmer
EP3327125B1 (de) 2010-10-29 2020-08-05 Sirna Therapeutics, Inc. Rna-interferenz-vermittelte inhibition von genexpression unter verwendung kurzer interferierender nukleinsäure (sina)
WO2012087772A1 (en) 2010-12-21 2012-06-28 Schering Corporation Indazole derivatives useful as erk inhibitors
EP2686313B1 (de) 2011-03-16 2016-02-03 Probiodrug AG Benzimidazolderivate als glutaminylcyclase-hemmer
US9629891B2 (en) 2011-10-17 2017-04-25 Nationwide Children's Hospital, Inc. Products and methods for aortic abdominal aneurysm
WO2013063214A1 (en) 2011-10-27 2013-05-02 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
EP3453762B1 (de) 2012-05-02 2021-04-21 Sirna Therapeutics, Inc. Sina-zusammensetzungen
WO2014039781A1 (en) 2012-09-07 2014-03-13 Massachusetts Eye & Ear Infirmary Treating hearing loss
MX2015004041A (es) 2012-09-28 2015-07-06 Merck Sharp & Dohme Compuestos novedosos que son inhibidores de erk.
RU2660349C2 (ru) 2012-11-28 2018-07-05 Мерк Шарп И Доум Корп. Композиции и способы для лечения злокачественной опухоли
US8846657B2 (en) 2012-12-20 2014-09-30 Merck Sharp & Dohme Corp. Substituted imidazopyridines as HDM2 inhibitors
EP2951180B1 (de) 2013-01-30 2018-05-02 Merck Sharp & Dohme Corp. 2,6,7,8-substituierte purine als hdm2-inhibitoren
US8859286B2 (en) 2013-03-14 2014-10-14 Viacyte, Inc. In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
WO2015104343A1 (en) * 2014-01-09 2015-07-16 Proyecto De Biomedicina Cima, S.L. New antifibrinolytic compounds
CN106488775A (zh) 2014-07-11 2017-03-08 基因泰克公司 Notch途径抑制
US20170314027A1 (en) 2014-08-06 2017-11-02 Massachusetts Eye And Ear Infirmary Increasing atoh1 life to drive sensorineural hair cell differentiantion
SG10201913841SA (en) 2015-07-24 2020-03-30 Oncotracker Inc Gamma secretase modulators for the treatment of immune system dysfunction
US11185536B2 (en) 2015-12-04 2021-11-30 Massachusetts Eye And Ear Infirmary Treatment of hearing loss by inhibition of casein kinase 1
CA3013038A1 (en) 2016-01-29 2017-08-03 Massachusetts Eye And Ear Infirmary Expansion and differentiation of inner ear supporting cells and methods of use thereof
EP3458076A4 (de) 2016-05-16 2020-01-22 The General Hospital Corporation Menschliche atemwegsstammzellen bei der züchtung von lungenepithel
RU2757276C2 (ru) 2016-12-16 2021-10-12 Пайплайн Терапьютикс, Инк. Способы лечения кохлеарной синаптопатии
EP3582782B1 (de) 2017-02-17 2023-06-07 Fred Hutchinson Cancer Center Kombinationstherapien zur behandlung von bcma-bedingten krebsarten und autoimmunerkrankungen
PL3461819T3 (pl) 2017-09-29 2020-11-30 Probiodrug Ag Inhibitory cyklazy glutaminylowej
EP3706742B1 (de) 2017-11-08 2023-03-15 Merck Sharp & Dohme LLC Prmt5-inhibitoren
WO2020016377A1 (en) 2018-07-19 2020-01-23 INSERM (Institut National de la Santé et de la Recherche Médicale) Combination for treating cancer
US11993602B2 (en) 2018-08-07 2024-05-28 Merck Sharp & Dohme Llc PRMT5 inhibitors
WO2020033284A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
EP4077282A4 (de) 2019-12-17 2023-11-08 Merck Sharp & Dohme LLC Prmt5-inhibitoren
KR20230005163A (ko) 2020-03-26 2023-01-09 씨젠 인크. 다발성 골수종 치료 방법
EP4244391A1 (de) 2020-11-16 2023-09-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Verfahren und zusammensetzungen zur vorhersage und behandlung von uvealem melanom
WO2024049931A1 (en) 2022-09-02 2024-03-07 Merck Sharp & Dohme Llc Exatecan-derived topoisomerase-1 inhibitors pharmaceutical compositions, and uses thereof
WO2024091437A1 (en) 2022-10-25 2024-05-02 Merck Sharp & Dohme Llc Exatecan-derived adc linker-payloads, pharmaceutical compositions, and uses thereof

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2802013A (en) 1954-02-12 1957-08-06 Searle & Co 2-(oxo and imino)-3-(phenyl and halophenyl)-tetrahydrofuransulfones and processes for the manufacture thereof
US2812330A (en) 1956-05-02 1957-11-05 Searle & Co Sulfone derivatives of 2, 6-piperidinedione
CA2191924A1 (en) * 1995-12-05 1997-06-06 Kevin Felsenstein 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives as inhibitors of .beta.-amyloid protein production
EP0863134A1 (de) 1997-03-07 1998-09-09 Merck Frosst Canada Inc. 2-(3,5-difluorophenyl)-3-(4-methylsulfonylphenyl)-2-cyclopenten-1-on zur Verwendung als Inhibitor der Cyclooxygenase-2
HRP990246A2 (en) * 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
CZ20013000A3 (cs) 1999-02-26 2002-02-13 Merck & Co., Inc. Nové sulfonamidové sloučeniny a jejich pouľití
AU2001240861B2 (en) * 2000-03-20 2006-03-30 Merck Frosst Canada Ltd Sulphonamido-substituted bridged bicycloalkyl derivatives
GB0108591D0 (en) * 2001-04-05 2001-05-23 Merck Sharp & Dohme Therapeutic agents
JP2005504042A (ja) * 2001-08-03 2005-02-10 シェーリング　コーポレイション γセクレターゼインヒビターのようなスルホンアミド誘導体
KR100927304B1 (ko) 2001-12-27 2009-11-18 다이이찌 세이야꾸 가부시기가이샤 β-아밀로이드 단백 생산·분비 저해제
DE10201392A1 (de) * 2002-01-16 2003-07-31 Bayer Ag Phenylsulfoxide und-sulfone

Also Published As

Publication number Publication date
ATE464287T1 (de) 2010-04-15
JP4653486B2 (ja) 2011-03-16
US20040121995A1 (en) 2004-06-24
GB0223038D0 (en) 2002-11-13
CA2500969A1 (en) 2004-04-15
AU2003269211B2 (en) 2009-05-28
EP1551799B1 (de) 2010-04-14
AU2003269211A1 (en) 2004-04-23
EP1551799A1 (de) 2005-07-13
AU2003269211C1 (en) 2009-10-15
US6890956B2 (en) 2005-05-10
WO2004031139A1 (en) 2004-04-15
JP2006501295A (ja) 2006-01-12

Similar Documents

Publication Publication Date Title
DE60332137D1 (en) Cyclohexyl-sulphone als gamma-sekretase-inhibitoren
GB0225474D0 (en) Therapeutic agents
GB0318447D0 (en) Therapeutic agents
MXPA05012323A (es) Sulfonamidas ciclicas para la inhibicion de gama-secretasa.
GB0225475D0 (en) Therapeutic agents
AU1074702A (en) Sulfamides as gamma-secretase inhibitors
MY135477A (en) 2-(2,6-dichlorophenyl)-diarylimidazoles
GB0025173D0 (en) Therapeutic agents
GB0223040D0 (en) Therapeutic compounds
DE59914996D1 (en) Heterocyclisch substituierte amide als calpainhemmer
WO2001066564A3 (en) Gamma-secretase inhibitors
EP1562897A4 (de) Phenylcarboxamide als beta-sekretase-hemmer zur behandlung von alzheimer
RS93604A (en) Substituted phenylacetamides and their use as glucokinase activators
MXPA04005847A (es) Compuestos derivados de 4-sulfuro/sulfoxido/sulfonil-1h-pirazolilo, para uso en enfermedades asociadas con el receptor 5-ht2c.
HK1087398A1 (en) 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases
ATE396174T1 (de) Hydroxyalkylaminderivate als beta-secretase- inhibitoren und deren verwendung zur behandlung der alzheimerschen krankheit oder ähnlicher krankheiten
MXPA03002911A (es) Compuestos quimicos.
ATE303384T1 (de) 1-biaryl-1,8-naphthyridin-4-one als phosphodieseterase-inhibitoren
WO2001058476A3 (en) Methods and compositions for treatment of alzheimer's disease by enhancing plasmin or plasmin-like activity
ATE446285T1 (de) Für die behandlung von alzheimer-krankheit und ähnlichen leiden geeignete 1-alkyl-3- thiosubstituierte indol-2-alkinsäuren
RS8504A (en) Novel cyclohexil sulphones
GB0606015D0 (en) therapeutic agents
MXPA04001419A (es) Isoxazolopiridinonas y su uso en el tratamiento de enfermedad de parkinson.
BR0316086A (pt) N-sulfonil-4-metileno amino-3-hidróxi-2-piridonas como agente microbicida
ATE464048T1 (de) Behandlung von alzheimer-krankheit und verwandten zuständen

Legal Events

Date Code Title Description
8364 No opposition during term of opposition