TWI297337B - Macrocyclic beta-secretase inhibitors - Google Patents
Macrocyclic beta-secretase inhibitors Download PDFInfo
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- TWI297337B TWI297337B TW094125432A TW94125432A TWI297337B TW I297337 B TWI297337 B TW I297337B TW 094125432 A TW094125432 A TW 094125432A TW 94125432 A TW94125432 A TW 94125432A TW I297337 B TWI297337 B TW I297337B
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- compound
- alkyl
- etoac
- aryl
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- 239000002439 beta secretase inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 157
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 42
- -1 geralkyl Chemical group 0.000 claims description 42
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- 238000011282 treatment Methods 0.000 claims description 23
- 230000004770 neurodegeneration Effects 0.000 claims description 21
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 230000001149 cognitive effect Effects 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
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- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
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- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- 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
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- General Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
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| US59189904P | 2004-07-28 | 2004-07-28 |
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| MX (1) | MX2007001102A (enExample) |
| TW (1) | TWI297337B (enExample) |
| WO (1) | WO2006014944A1 (enExample) |
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| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| CA2593268A1 (en) * | 2005-01-13 | 2006-07-20 | Novartis Ag | Macrocyclic compounds useful as bace inhibitors |
| GB0500683D0 (en) | 2005-01-13 | 2005-02-23 | Novartis Ag | Organic compounds |
| BRPI0612072A2 (pt) | 2005-06-14 | 2010-10-19 | Schering Corp | inibidores da aspartil protease |
| ES2350854T3 (es) * | 2005-06-14 | 2011-01-27 | Schering Corporation | Inhibidores de aspartil proteasa. |
| RU2432362C2 (ru) | 2005-11-30 | 2011-10-27 | Эбботт Лэборетриз | Моноклональные антитела и их применения |
| EP1954718B1 (en) | 2005-11-30 | 2014-09-03 | AbbVie Inc. | Anti-a globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
| WO2007146225A2 (en) | 2006-06-12 | 2007-12-21 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| KR20090041387A (ko) * | 2006-07-20 | 2009-04-28 | 노파르티스 아게 | 마크로시클릭 락탐 |
| CA2667071A1 (en) | 2006-10-06 | 2008-04-17 | Merck & Co., Inc. | Macrocyclic spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease |
| JP5379692B2 (ja) | 2006-11-09 | 2013-12-25 | プロビオドルグ エージー | 潰瘍、癌及び他の疾患の治療のためのグルタミニルシクラーゼの阻害薬としての３−ヒドロキシ−１，５−ジヒドロ−ピロール−２−オン誘導体 |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| WO2008065141A1 (en) | 2006-11-30 | 2008-06-05 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
| JP2010512389A (ja) | 2006-12-12 | 2010-04-22 | シェーリング コーポレイション | アスパルチルプロテアーゼ阻害剤 |
| EP2486928A1 (en) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
| ZA200905537B (en) | 2007-03-01 | 2010-10-27 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| EP2200990A1 (en) | 2007-09-06 | 2010-06-30 | Schering Corporation | Gamma secretase modulators |
| US8487099B2 (en) | 2007-11-05 | 2013-07-16 | Merck Sharp & Dohme Corp. | Gamma secretase modulators |
| WO2009076352A1 (en) | 2007-12-11 | 2009-06-18 | Schering Corporation | Gamma secretase modulators |
| MX2010011563A (es) | 2008-04-22 | 2010-11-12 | Schering Corp | Compuestos 2-imino-3-metil pirrolo pirimidinona fenil-sustituidos como inhibidores de enzima de escision de proteina precursora amiloide sitio beta-1, composiciones y su uso. |
| CN102282145A (zh) | 2008-11-13 | 2011-12-14 | 先灵公司 | γ分泌酶调节剂 |
| US8759337B2 (en) | 2008-12-22 | 2014-06-24 | Merck Sharp & Dohme Corp. | Gamma secretase modulators |
| TW201035103A (en) | 2008-12-22 | 2010-10-01 | Schering Corp | Gamma secretase modulators |
| US20120245158A1 (en) | 2009-06-16 | 2012-09-27 | Xianhai Huang | Gamma secretase modulators |
| EP2443121A2 (en) | 2009-06-16 | 2012-04-25 | Schering Corporation | Gamma secretase modulators |
| WO2010147973A1 (en) | 2009-06-16 | 2010-12-23 | Schering Corporation | Gamma secretase modulators |
| EP2475428B1 (en) | 2009-09-11 | 2015-07-01 | Probiodrug AG | Heterocylcic derivatives as inhibitors of glutaminyl cyclase |
| US8563543B2 (en) | 2009-10-08 | 2013-10-22 | Merck Sharp & Dohme Corp. | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2485590B1 (en) | 2009-10-08 | 2015-01-07 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| US8569310B2 (en) | 2009-10-08 | 2013-10-29 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use |
| JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
| NZ602312A (en) | 2010-03-10 | 2014-02-28 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| WO2011130377A2 (en) | 2010-04-15 | 2011-10-20 | Abbott Laboratories | Amyloid-beta binding proteins |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| EP3533803B1 (en) | 2010-08-14 | 2021-10-27 | AbbVie Inc. | Anti-amyloid-beta antibodies |
| JP6050264B2 (ja) | 2011-03-16 | 2016-12-21 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体 |
| US9221839B2 (en) | 2011-04-07 | 2015-12-29 | Merck Sharp & Dohme Corp. | C5-C6 oxacyclic-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
| AU2012298983A1 (en) | 2011-08-22 | 2014-02-27 | Merck Sharp & Dohme Corp. | 2-spiro-substituted iminothiazines and their mono-and dioxides as BACE inhibitors, compositions and their use |
| CN106902108B (zh) | 2012-03-19 | 2020-07-21 | 巴克老龄化研究所 | App特异性bace抑制剂(asbi)及其用途 |
| WO2014056816A1 (en) | 2012-10-10 | 2014-04-17 | F. Hoffmann-La Roche Ag | COMBINATION OF AN Aβ ANTIBODY AND A BACE INHIBITOR |
| US9422277B2 (en) | 2012-10-17 | 2016-08-23 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
| WO2014062553A1 (en) | 2012-10-17 | 2014-04-24 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2956443B1 (en) | 2013-02-12 | 2019-09-25 | Buck Institute For Research On Aging | Hydantoins that modulate bace-mediated app processing |
| CN105175488A (zh) * | 2015-09-07 | 2015-12-23 | 西北农林科技大学 | 一种具有抗老年痴呆症活性的化合物及其制备方法 |
| AU2018308088B2 (en) | 2017-07-25 | 2025-05-29 | Truebinding, Inc. | Treating cancer by blocking the interaction of TIM-3 and its ligand |
| DK3461819T3 (da) | 2017-09-29 | 2020-08-10 | Probiodrug Ag | Inhibitorer af glutaminylcyklase |
| CA3127113A1 (en) | 2019-01-30 | 2020-08-06 | Dongxu Sun | Anti-gal3 antibodies and uses thereof |
| AU2021278935A1 (en) | 2020-05-26 | 2022-12-08 | Truebinding, Inc. | Methods of treating inflammatory diseases by blocking Galectin-3 |
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| FI902006A0 (fi) | 1987-10-21 | 1990-04-20 | Upjohn Co | Foerfarande foer framstaellning av renininhibitorer innehaollande 1-amino-2-hydroxi-2-heterocyklisk etylrest. |
| CN1217920C (zh) | 2000-06-30 | 2005-09-07 | 艾兰制药公司 | 治疗早老性痴呆的化合物 |
| PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| US6846813B2 (en) | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| JP2004534017A (ja) | 2001-04-27 | 2004-11-11 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｂａｃｅのインヒビター |
| US6969709B2 (en) | 2001-06-12 | 2005-11-29 | Pharmacia & Upjohn Company | Macrocycles useful in the treatment of Alzheimer's disease |
| WO2002100399A1 (en) * | 2001-06-12 | 2002-12-19 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| US20040171614A1 (en) * | 2002-02-06 | 2004-09-02 | Schering-Plough Corporation | Novel gamma secretase inhibitors |
| EP1562897B1 (en) * | 2002-11-12 | 2009-09-16 | Merck & Co., Inc. | Phenylcarboxamide beta-secretase inhibitors for the treatment of alzheimer s disease |
| WO2004062625A2 (en) * | 2003-01-07 | 2004-07-29 | Merck & Co., Inc. | Macrocyclic beta-secretase inhibitors for treatment of alzheimer's disease |
| WO2006009655A1 (en) * | 2004-06-16 | 2006-01-26 | Wyeth | Diphenylimidazopyrimidine and -imidazole amines as inhibitors of b-secretase |
| AU2005264915A1 (en) | 2004-06-16 | 2006-01-26 | Wyeth | Amino-5,5-diphenylimidazolone derivatives for the inhibition of beta-secretase |
| EP1896448A1 (en) | 2005-06-30 | 2008-03-12 | Wyeth | AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION |
| TW200738683A (en) | 2005-06-30 | 2007-10-16 | Wyeth Corp | Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation |
| TW200730523A (en) | 2005-07-29 | 2007-08-16 | Wyeth Corp | Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation |
| JP2009509957A (ja) | 2005-09-26 | 2009-03-12 | ワイス | β−セクレターゼ阻害剤としてのアミノ−５−［４−（ジフルオロメトキシ）フェニル］−５−フェニルイミダゾロン化合物 |
| US20090099217A1 (en) | 2006-04-05 | 2009-04-16 | Astex Therapeutics Ltd. | 2-Aminopyrimidin-4-Ones And Their Use For Treating Or Preventing Alpha Beta-Related Pathologies |
| TW200815449A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds II |
| TW200815443A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds I |
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| TW200815447A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds IV |
| TW200815349A (en) | 2006-06-22 | 2008-04-01 | Astrazeneca Ab | New compounds |
-
2005
- 2005-07-26 JP JP2007523724A patent/JP2008508289A/ja active Pending
- 2005-07-26 MX MX2007001102A patent/MX2007001102A/es active IP Right Grant
- 2005-07-26 WO PCT/US2005/026468 patent/WO2006014944A1/en not_active Ceased
- 2005-07-26 AR ARP050103099A patent/AR050184A1/es not_active Application Discontinuation
- 2005-07-26 EP EP05776414A patent/EP1781644B1/en not_active Expired - Lifetime
- 2005-07-26 US US11/189,346 patent/US7652003B2/en not_active Expired - Lifetime
- 2005-07-26 AT AT05776414T patent/ATE396990T1/de not_active IP Right Cessation
- 2005-07-26 ES ES05776414T patent/ES2306200T3/es not_active Expired - Lifetime
- 2005-07-26 DE DE602005007245T patent/DE602005007245D1/de not_active Expired - Lifetime
- 2005-07-26 CA CA002575340A patent/CA2575340A1/en not_active Abandoned
- 2005-07-26 CN CN2005800323948A patent/CN101027297B/zh not_active Expired - Fee Related
- 2005-07-27 TW TW094125432A patent/TWI297337B/zh not_active IP Right Cessation
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2009
- 2009-10-01 US US12/571,840 patent/US8012953B2/en not_active Expired - Lifetime
Also Published As
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|---|---|
| HK1102328A1 (en) | 2007-11-16 |
| EP1781644A1 (en) | 2007-05-09 |
| JP2008508289A (ja) | 2008-03-21 |
| ES2306200T3 (es) | 2008-11-01 |
| CA2575340A1 (en) | 2006-02-09 |
| WO2006014944A1 (en) | 2006-02-09 |
| US7652003B2 (en) | 2010-01-26 |
| CN101027297A (zh) | 2007-08-29 |
| US20100178294A1 (en) | 2010-07-15 |
| DE602005007245D1 (enExample) | 2008-07-10 |
| US20060040948A1 (en) | 2006-02-23 |
| MX2007001102A (es) | 2007-04-13 |
| TW200607807A (en) | 2006-03-01 |
| US8012953B2 (en) | 2011-09-06 |
| AR050184A1 (es) | 2006-10-04 |
| CN101027297B (zh) | 2010-09-08 |
| EP1781644B1 (en) | 2008-05-28 |
| ATE396990T1 (de) | 2008-06-15 |
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