ATE464287T1 - Cyclohexyl-sulphone als gamma-sekretase- inhibitoren - Google Patents

Cyclohexyl-sulphone als gamma-sekretase- inhibitoren

Info

Publication number
ATE464287T1
ATE464287T1 AT03750987T AT03750987T ATE464287T1 AT E464287 T1 ATE464287 T1 AT E464287T1 AT 03750987 T AT03750987 T AT 03750987T AT 03750987 T AT03750987 T AT 03750987T AT E464287 T1 ATE464287 T1 AT E464287T1
Authority
AT
Austria
Prior art keywords
gamma secretase
secretase inhibitors
sulphones
cyclohexyl
cyclohexyl sulphones
Prior art date
Application number
AT03750987T
Other languages
English (en)
Inventor
Ian Churcher
Timothy Harrison
Sonia Kerrad
Alan John Nadin
Andrew Owens
Duncan Edward Shaw
Joanne Thomson
Susannah Williams
Original Assignee
Merck Sharp & Dohme
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 & Dohme filed Critical Merck Sharp & Dohme
Application granted granted Critical
Publication of ATE464287T1 publication Critical patent/ATE464287T1/de

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)
AT03750987T 2002-10-04 2003-09-25 Cyclohexyl-sulphone als gamma-sekretase- inhibitoren ATE464287T1 (de)

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
ATE464287T1 true ATE464287T1 (de) 2010-04-15

Family

ID=9945312

Family Applications (1)

Application Number Title Priority Date Filing Date
AT03750987T ATE464287T1 (de) 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
WO2003055850A1 (fr) 2001-12-27 2003-07-10 Daiichi Pharmaceutical Co., Ltd. Inhibiteurs de la production/secretion de la proteine amyloide-$g(b)
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
AU2005264917A1 (en) * 2004-06-16 2006-01-26 Wyeth Diphenylimidazopyrimidine and -imidazole amines as inhibitors of B-secretase
CN101103034A (zh) * 2005-01-14 2008-01-09 惠氏公司 抑制β-分泌酶的氨基-咪唑酮
US20090215775A1 (en) * 2005-05-17 2009-08-27 Huw David Lewis Sulphonamido-Substituted Cyclohexyl Sulphones for Treatment of Cancer
WO2006123182A2 (en) 2005-05-17 2006-11-23 Merck Sharp & Dohme Limited Cyclohexyl sulphones for treatment of cancer
GB0513747D0 (en) * 2005-07-06 2005-08-10 Merck Sharp & Dohme Therapeutic compounds
WO2011053822A2 (en) 2009-11-01 2011-05-05 The Brigham And Women's Hospital, Inc. Notch inhibition in the treatment and prevention of obesity and metabolic syndrome
US9567396B2 (en) 2006-03-07 2017-02-14 Evonik Degussa Gmbh Notch inhibition in the prevention of vein graft failure
US8133857B2 (en) * 2006-03-07 2012-03-13 The Brigham and Women's FHospital, Inc. NOTCH inhibition in the treatment of atherosclerosis
WO2008055945A1 (en) 2006-11-09 2008-05-15 Probiodrug Ag 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases
CA2669693C (en) 2006-11-15 2018-06-12 Massachusetts Eye & Ear Infirmary Generation of inner ear cells
EP2091948B1 (de) 2006-11-30 2012-04-18 Probiodrug AG Neue inhibitoren von glutaminylcyclase
EP2121633A2 (de) 2007-02-12 2009-11-25 Merck & Co., Inc. Piperazinderivate zur behandlung von alzheimer-krankheit und verwandten leiden
MX2009009234A (es) 2007-03-01 2009-12-01 Probiodrug Ag Uso nuevo de inhibidores de ciclasa de glutaminilo.
EP2865670B1 (de) 2007-04-18 2017-01-11 Probiodrug AG Thioharnstoffderivative als Glutaminylcyclaseinhibitoren
US8377886B2 (en) * 2007-09-14 2013-02-19 Albert Einstein College Of Medicine Of Yeshiva University Use of gamma secretase inhibitors and notch pathway inhibitors for treatment and prevention of renal disease
WO2009128057A2 (en) 2008-04-18 2009-10-22 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al Psycho-pharmaceuticals
CA2721910A1 (en) * 2008-04-23 2009-10-29 Merck Sharp & Dohme Corp. Cyclobutyl sulfones as notch sparing gamma secretase inhibitors
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
WO2011009064A1 (en) * 2009-07-17 2011-01-20 The J. David Gladstone Institutes Methods of controlling cell proliferation
ES2548913T3 (es) 2009-09-11 2015-10-21 Probiodrug Ag Derivados heterocíclicos como inhibidores de glutaminil ciclasa
AU2010295481A1 (en) * 2009-09-18 2012-03-08 Zalicus Pharmaceuticals Ltd. Aryl sulphone derivatives as calcium channel blockers
WO2011046771A1 (en) 2009-10-14 2011-04-21 Schering Corporation SUBSTITUTED PIPERIDINES THAT INCREASE p53 ACTIVITY AND THE USES THEREOF
ES2586231T3 (es) 2010-03-03 2016-10-13 Probiodrug Ag Inhibidores de glutaminil ciclasa
AU2011226074B2 (en) 2010-03-10 2015-01-22 Vivoryon Therapeutics N.V. Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5)
EP2560953B1 (de) 2010-04-21 2016-01-06 Probiodrug AG Hemmer der glutaminylzyklase
EP2584903B1 (de) 2010-06-24 2018-10-24 Merck Sharp & Dohme Corp. Neue heterozyklische verbindungen als erk-hemmer
WO2012018754A2 (en) 2010-08-02 2012-02-09 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF CATENIN (CADHERIN-ASSOCIATED PROTEIN), BETA 1 (CTNNB1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
EP3587574B1 (de) 2010-08-17 2022-03-16 Sirna Therapeutics, Inc. Rna-interferenz-vermittelte hemmung der hepatitis b-virus (hbv)-genexpression mittels kurzer interferierender nukleinsäure (sina)
WO2012030685A2 (en) 2010-09-01 2012-03-08 Schering Corporation Indazole derivatives useful as erk inhibitors
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
EP2632472B1 (de) 2010-10-29 2017-12-13 Sirna Therapeutics, Inc. Durch rna-interferenz vermittelte inhibition einer genexpression unter verwendung von short-interfering-nukleinsäuren (sina)
WO2012087772A1 (en) 2010-12-21 2012-06-28 Schering Corporation Indazole derivatives useful as erk inhibitors
US8530670B2 (en) 2011-03-16 2013-09-10 Probiodrug Ag Inhibitors
US9629891B2 (en) 2011-10-17 2017-04-25 Nationwide Children's Hospital, Inc. Products and methods for aortic abdominal aneurysm
US9023865B2 (en) 2011-10-27 2015-05-05 Merck Sharp & Dohme Corp. Compounds that are ERK inhibitors
EP3919620A1 (de) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Zusammensetzungen mit kurzer interferierender nukleinsäure (sina)
EP3970725A1 (de) 2012-09-07 2022-03-23 Massachusetts Eye & Ear Infirmary Ein gamma-sekretase-inhibitor zur behandlung von gehörverlust
US9233979B2 (en) 2012-09-28 2016-01-12 Merck Sharp & Dohme Corp. Compounds that are ERK inhibitors
PL2925888T3 (pl) 2012-11-28 2018-03-30 Merck Sharp & Dohme Corp. Kompozycje i sposoby do stosowania w leczeniu nowotworów
CA2895504A1 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Substituted imidazopyridines as hdm2 inhibitors
WO2014120748A1 (en) 2013-01-30 2014-08-07 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as hdm2 inhibitors
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
US20160194368A1 (en) 2013-09-03 2016-07-07 Moderna Therapeutics, Inc. Circular polynucleotides
WO2015104343A1 (en) * 2014-01-09 2015-07-16 Proyecto De Biomedicina Cima, S.L. New antifibrinolytic compounds
EP3166627A1 (de) 2014-07-11 2017-05-17 Genentech, Inc. Notch-signalweghemmung
WO2016022776A2 (en) 2014-08-06 2016-02-11 Massachusetts Eye And Ear Infirmary Increasing atoh1 life to drive sensorineural hair cell differentiantion
MX2018000999A (es) 2015-07-24 2018-11-09 Oncotracker Inc Moduladores de gamma secretasa para el tratamiento de disfuncion del sistema inmunologico.
WO2017096233A1 (en) 2015-12-04 2017-06-08 Massachusetts Eye And Ear Infirmary Treatment of hearing loss by inhibition of casein kinase 1
KR20180117628A (ko) 2016-01-29 2018-10-29 매사추세츠 아이 앤드 이어 인퍼머리 내이 지지 세포의 확장 및 분화 및 그의 사용 방법
EP3458076A4 (de) 2016-05-16 2020-01-22 The General Hospital Corporation Menschliche atemwegsstammzellen bei der züchtung von lungenepithel
JP6904612B2 (ja) 2016-12-16 2021-07-21 パイプライン セラピューティクス， インコーポレイテッド 蝸牛シナプス障害を処置する方法
ES2949364T3 (es) 2017-02-17 2023-09-28 Fred Hutchinson Cancer Center Terapias de combinación para el tratamiento de cánceres y trastornos autoinmunitarios relacionados con BCMA
DK3461819T3 (da) 2017-09-29 2020-08-10 Probiodrug Ag Inhibitorer af glutaminylcyklase
US10947234B2 (en) 2017-11-08 2021-03-16 Merck Sharp & Dohme Corp. PRMT5 inhibitors
US20210290633A1 (en) 2018-07-19 2021-09-23 INSERM (Insstitut National de la Santé et de la Recherche Médicale) Combination for treating cancer
US11981701B2 (en) 2018-08-07 2024-05-14 Merck Sharp & Dohme Llc PRMT5 inhibitors
US11993602B2 (en) 2018-08-07 2024-05-28 Merck Sharp & Dohme Llc PRMT5 inhibitors
CA3160153A1 (en) 2019-12-17 2021-06-24 Michelle Machacek Prmt5 inhibitors
MX2022011800A (es) 2020-03-26 2023-01-19 Seagen Inc Metodos para tratar mieloma multiple.
WO2022101481A1 (en) 2020-11-16 2022-05-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for predicting and treating uveal melanoma
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
EP1159263A1 (de) 1999-02-26 2001-12-05 Merck & Co., Inc. Sulfonamid-verbindungen und anwendungen davon
AU4086101A (en) * 2000-03-20 2001-10-03 Merck Sharp & Dohme Sulphonamido-substituted bridged bicycloalkyl derivatives
GB0108591D0 (en) * 2001-04-05 2001-05-23 Merck Sharp & Dohme Therapeutic agents
CN1780621A (zh) * 2001-08-03 2006-05-31 先灵公司 作为γ分泌酶抑制剂的磺酰胺衍生物
WO2003055850A1 (fr) 2001-12-27 2003-07-10 Daiichi Pharmaceutical Co., Ltd. Inhibiteurs de la production/secretion de la proteine amyloide-$g(b)
DE10201392A1 (de) 2002-01-16 2003-07-31 Bayer Ag Phenylsulfoxide und-sulfone

Also Published As

Publication number Publication date
AU2003269211B2 (en) 2009-05-28
GB0223038D0 (en) 2002-11-13
DE60332137D1 (en) 2010-05-27
US6890956B2 (en) 2005-05-10
JP4653486B2 (ja) 2011-03-16
CA2500969A1 (en) 2004-04-15
AU2003269211A1 (en) 2004-04-23
EP1551799B1 (de) 2010-04-14
JP2006501295A (ja) 2006-01-12
EP1551799A1 (de) 2005-07-13
WO2004031139A1 (en) 2004-04-15
US20040121995A1 (en) 2004-06-24
AU2003269211C1 (en) 2009-10-15

Similar Documents

Publication Publication Date Title
ATE464287T1 (de) Cyclohexyl-sulphone als gamma-sekretase- inhibitoren
ATE368031T1 (de) Neue gamma secretase inhibitoren
DE602004011767D1 (de) Zyklohexylsulfone als gamma-sekretase-inhibitoren
DE60335731D1 (de) Sulfonamide, sulfamate und sulfamide als gamma-secretase-hemmer
ATE302753T1 (de) Sulfamide als gamma-secretase-inhibitoren
DE60134874D1 (de) Benzodiazepin-derivate als gamma-secretase inhibitoren
DE60112055D1 (de) Inhibitoren von gamma-secretase
DE60312017D1 (de) Sulfonderivate zur hemmung von gamma-secretase
DE60329533D1 (de) Cyclische sulfamide zur inhibierung von gamma-sekretase
DE60310576D1 (en) 2-hydroxy-6-phenylphenanthridine als pde-4-hemmer
ATE443043T1 (de) Phenylcarboxamide als beta-sekretase-hemmer zur behandlung von alzheimer
ATE427300T1 (de) Heterocyclisch substituierte amide als calpainhemmer
ATE433981T1 (de) Heterocyclische verbindungen
DE60311662D1 (en) 3-hydroxy-6-phenylphenanthridine als pde-4 inhibitoren
ATE396174T1 (de) Hydroxyalkylaminderivate als beta-secretase- inhibitoren und deren verwendung zur behandlung der alzheimerschen krankheit oder ähnlicher krankheiten
ATE477256T1 (de) Thienylverbindungen
ATE446285T1 (de) Für die behandlung von alzheimer-krankheit und ähnlichen leiden geeignete 1-alkyl-3- thiosubstituierte indol-2-alkinsäuren
ATE516027T1 (de) Orazamid orotat zur vorbeugung von leberschäden
ATE530525T1 (de) Piperidine und verwandte verbindungen zur behandlung von demenz
ATE519740T1 (de) Tetrahydroindolderivate zur behandlung von alzheimer-krankheit
TW200505836A (en) Cyclic sulfonamides for inhibition of gamma-secretase
DE60305520D1 (de) 2" oxo-voruscharin und derivaten
DE60319743D1 (de) Phthalazinderivate als phosphodiesterase-4-hemmer

Legal Events

Date Code Title Description
RER Ceased as to paragraph 5 lit. 3 law introducing patent treaties