CN1078886C - 抑制β－淀粉样蛋白产生的抑制剂 - Google Patents

抑制β－淀粉样蛋白产生的抑制剂 Download PDF

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Publication number
CN1078886C
CN1078886C CN94193598A CN94193598A CN1078886C CN 1078886 C CN1078886 C CN 1078886C CN 94193598 A CN94193598 A CN 94193598A CN 94193598 A CN94193598 A CN 94193598A CN 1078886 C CN1078886 C CN 1078886C
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CN
China
Prior art keywords
alkyl
benzyl
group
compound
amino
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 - Fee Related
Application number
CN94193598A
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English (en)
Chinese (zh)
Other versions
CN1132504A (zh
Inventor
B·科尔戴尔
D·舍林
N·P·琵特
J·N·海加基
V·万多塞拉尔
M·R·安格拉斯特罗
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.)
Sixi Oswald - Nova Co
Aventis Pharmaceuticals Inc
Original Assignee
Scios Nova
Merrell Dow Pharmaceuticals Inc
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Filing date
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Publication of CN1132504A publication Critical patent/CN1132504A/zh
Application granted granted Critical
Publication of CN1078886C publication Critical patent/CN1078886C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • 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
    • C07D295/16—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 acylated on ring nitrogen atoms
    • C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • 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

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hospice & Palliative Care (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Psychiatry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN94193598A 1993-10-01 1994-09-20 抑制β－淀粉样蛋白产生的抑制剂 Expired - Fee Related CN1078886C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP93402398 1993-10-01
EP93402398.7 1993-10-01

Publications (2)

Publication Number Publication Date
CN1132504A CN1132504A (zh) 1996-10-02
CN1078886C true CN1078886C (zh) 2002-02-06

Family

ID=8214751

Family Applications (1)

Application Number Title Priority Date Filing Date
CN94193598A Expired - Fee Related CN1078886C (zh) 1993-10-01 1994-09-20 抑制β－淀粉样蛋白产生的抑制剂

Country Status (19)

Country Link
EP (1) EP0721449B1 (https=)
JP (1) JPH09505281A (https=)
KR (1) KR100316865B1 (https=)
CN (1) CN1078886C (https=)
AT (1) ATE211129T1 (https=)
AU (1) AU687449B2 (https=)
CA (1) CA2171882C (https=)
DE (1) DE69429527T2 (https=)
DK (1) DK0721449T3 (https=)
ES (1) ES2170104T3 (https=)
FI (1) FI961438A0 (https=)
HU (1) HU221629B1 (https=)
IL (1) IL111078A (https=)
NO (1) NO308029B1 (https=)
NZ (1) NZ274074A (https=)
PT (1) PT721449E (https=)
TW (1) TW264480B (https=)
WO (1) WO1995009838A1 (https=)
ZA (1) ZA947529B (https=)

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EP0763055B1 (en) * 1994-06-02 1999-11-03 Merrell Pharmaceuticals Inc. Perfluoroalkyl ketone inhibitors of elastase and processes for making the same
DE69522940T2 (de) * 1994-06-02 2002-04-04 Merrell Pharmaceuticals Inc., Cincinnati Acylierte enolderivate als vorläufdrogen von elastaseinhibitoren
US5804560A (en) * 1995-01-06 1998-09-08 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5691368A (en) * 1995-01-11 1997-11-25 Hoechst Marion Roussel, Inc. Substituted oxazolidine calpain and/or cathepsin B inhibitors
WO1996039194A1 (en) * 1995-06-06 1996-12-12 Athena Neurosciences, Inc. Novel cathepsin and methods and compositions for inhibition thereof
US5783434A (en) * 1995-06-06 1998-07-21 Tung; Jay S. Cathepsin and methods and compositions for inhibition thereof
US5849711A (en) * 1995-06-06 1998-12-15 Athena Neurosciences, Inc. Cathepsin and methods and compositions for inhibition thereof
US6172044B1 (en) 1995-12-01 2001-01-09 Aventis Pharmaceuticals Inc. Acylated enol derivative of α-ketoesters and α-ketoamides
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
US5703129A (en) * 1996-09-30 1997-12-30 Bristol-Myers Squibb Company 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives as inhibitors of β-amyloid protein production
US6642261B2 (en) 1997-11-21 2003-11-04 Athena Neurosciences, Inc. N-(aryl/heteroarylacety) amino acid esters, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6117901A (en) * 1996-11-22 2000-09-12 Athena Neurosciences, Inc. N-(aryl/heteroarylacetyl) amino acid esters, pharmaceutical compositions comprising same, and methods for use
US6153652A (en) 1996-11-22 2000-11-28 Elan Pharmaceuticals, Inc. N-(aryl/heteroaryl/alkylacetyl) amino acid amides, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6096782A (en) 1996-11-22 2000-08-01 Athena Neurosciences, Inc. N-(aryl/heteroaryl) amino acid derivatives pharmaceutical compositions comprising same and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6191166B1 (en) 1997-11-21 2001-02-20 Elan Pharmaceuticals, Inc. Methods and compounds for inhibiting β-amyloid peptide release and/or its synthesis
WO1998022493A2 (en) * 1996-11-22 1998-05-28 Elan Pharmaceuticals, Inc. N-(ARYL/HETEROARYL) AMINO ACID DERIVATIVES, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, AND METHODS FOR INHIBITING β-AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS BY USE OF SUCH COMPOUNDS
AR016751A1 (es) * 1996-11-22 2001-08-01 Athena Neurosciences Inc Metodo para inhibir la liberacion del peptido beta-amiloide en una celula, composicion farmaceutica y compuestos utiles en dicho metodo
US6211235B1 (en) 1996-11-22 2001-04-03 Elan Pharmaceuticals, Inc. Compounds for inhibiting β-amyloid peptide release and/or its synthesis
US6207710B1 (en) 1996-11-22 2001-03-27 Elan Pharmaceuticals, Inc. Compounds for inhibiting β-amyloid peptide release and/or its synthesis
DE19648793A1 (de) 1996-11-26 1998-05-28 Basf Ag Neue Benzamide und deren Anwendung
US6635632B1 (en) 1996-12-23 2003-10-21 Athena Neurosciences, Inc. Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6683075B1 (en) 1996-12-23 2004-01-27 Athena Neurosciences, Inc. Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use
US6506782B1 (en) 1998-02-27 2003-01-14 Athena Neurosciences, Inc. Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6509331B1 (en) 1998-06-22 2003-01-21 Elan Pharmaceuticals, Inc. Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6569851B1 (en) 1998-06-22 2003-05-27 Elan Pharmaceutials, Inc. Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6958330B1 (en) 1998-06-22 2005-10-25 Elan Pharmaceuticals, Inc. Polycyclic α-amino-ε-caprolactams and related compounds
US6552013B1 (en) 1998-06-22 2003-04-22 Elan Pharmaceuticals, Inc. Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6528505B1 (en) 1998-06-22 2003-03-04 Elan Pharmaceuticals, Inc. Cyclic amino acid compounds pharmaceutical compositions comprising same and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6774125B2 (en) 1998-06-22 2004-08-10 Elan Pharmaceuticals, Inc. Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
US6737038B1 (en) 1998-11-12 2004-05-18 Bristol-Myers Squibb Company Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
WO2000051998A1 (en) * 1999-03-02 2000-09-08 Boehringer Ingelheim Pharmaceuticals, Inc. Compounds useful as reversible inhibitors of cathepsin s
US6420364B1 (en) 1999-09-13 2002-07-16 Boehringer Ingelheim Pharmaceuticals, Inc. Compound useful as reversible inhibitors of cysteine proteases
US6878363B2 (en) 2000-05-17 2005-04-12 Bristol-Myers Squibb Pharma Company Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
US6613801B2 (en) * 2000-05-30 2003-09-02 Transtech Pharma, Inc. Method for the synthesis of compounds of formula I and their uses thereof
US7087632B2 (en) 2001-03-05 2006-08-08 Transtech Pharma, Inc. Benzimidazole derivatives as therapeutic agents
EP1268450A1 (en) 2000-06-01 2003-01-02 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of a-beta protein production
US6432944B1 (en) 2000-07-06 2002-08-13 Bristol-Myers Squibb Company Benzodiazepinone β-amyloid inhibitors: arylacetamidoalanyl derivatives
CN1494425B (zh) 2001-03-05 2011-12-07 特兰斯泰克制药公司 用作治疗剂的羧酰胺衍生物
JP4481011B2 (ja) 2002-03-05 2010-06-16 トランス テック ファーマ，インコーポレイテッド リガンドのｒａｇｅとの相互作用を阻害する単環式および二環式アゾール誘導体
US7576206B2 (en) 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
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ES2467923T3 (es) 2009-09-30 2014-06-13 Transtech Pharma, Llc Derivados de imidazol substituidos para el tratamiento de la enfermedad de Alzheimer
AU2010341530B2 (en) 2009-12-22 2016-03-10 Cephalon, Inc. Proteasome inhibitors and processes for their preparation, purification and use
US9717710B2 (en) 2012-10-05 2017-08-01 Vtv Therapeutics Llc Treatment of mild and moderate Alzheimer's disease
CN108440584B (zh) * 2015-12-30 2020-08-07 南京中硼联康医疗科技有限公司 用于制备和β淀粉样蛋白特异性结合的化合物的中间体的制备方法
JP7164521B2 (ja) 2016-06-21 2022-11-01 オリオン・オフサルモロジー・エルエルシー 炭素環式プロリンアミド誘導体
HUE064412T2 (hu) 2016-06-21 2024-03-28 Orion Ophthalmology LLC Heterociklusos prolinamid-származékok
CN111867549B (zh) * 2018-02-02 2024-01-05 安捷伦科技有限公司 用于使用封闭的2-aa进行聚糖分析的方法和试剂盒
WO2019190822A1 (en) 2018-03-28 2019-10-03 Vtv Therapeutics Llc Crystalline forms of [3-(4- {2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1h-imidazol-4-yl} -phenoxy)-propyl]-diethyl-amine
WO2019190823A1 (en) 2018-03-28 2019-10-03 Vtv Therapeutics Llc Pharmaceutically acceptable salts of [3-(4- {2-butyl-1-[4-(4-chlorophenoxy)-phenyl]-1h-imidazol-4-yl} -phenoxy)-propyl]-diethyl-amine
JP7464591B2 (ja) 2018-10-10 2024-04-09 ブイティーブイ・セラピューティクス・エルエルシー ［３－（４－｛２－ブチル－１－［４－（４－クロロ－フェノキシ）－フェニル］－１ｈ－イミダゾール－４－イル｝－フェノキシ）－プロピル］－ジエチル－アミンの代謝産物

Citations (1)

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Publication number Priority date Publication date Assignee Title
WO1992014696A2 (en) * 1991-02-22 1992-09-03 The Du Pont Merck Pharmaceutical Company SUBSTITUTED α-AMINOALDEHYDES AND DERIVATIVES

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Also Published As

Publication number Publication date
JPH09505281A (ja) 1997-05-27
FI961438A7 (fi) 1996-03-29
NO308029B1 (no) 2000-07-10
HU9600832D0 (en) 1996-05-28
FI961438L (fi) 1996-03-29
CA2171882A1 (en) 1995-04-13
CN1132504A (zh) 1996-10-02
DE69429527T2 (de) 2002-07-18
EP0721449A1 (en) 1996-07-17
ZA947529B (en) 1995-05-29
KR100316865B1 (ko) 2002-11-29
PT721449E (pt) 2002-06-28
ES2170104T3 (es) 2002-08-01
IL111078A0 (en) 1994-11-28
NZ274074A (en) 1997-11-24
HUT74004A (en) 1996-10-28
KR960704839A (ko) 1996-10-09
IL111078A (en) 1999-03-12
AU687449B2 (en) 1998-02-26
FI961438A0 (fi) 1996-03-29
NO961326L (no) 1996-04-01
EP0721449B1 (en) 2001-12-19
NO961326D0 (no) 1996-04-01
HU221629B1 (hu) 2002-12-28
ATE211129T1 (de) 2002-01-15
DE69429527D1 (de) 2002-01-31
TW264480B (https=) 1995-12-01
AU7799894A (en) 1995-05-01
WO1995009838A1 (en) 1995-04-13
CA2171882C (en) 2001-12-04
DK0721449T3 (da) 2002-04-22

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