JP6050264B2 - 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 - Google Patents

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 Download PDF

Info

Publication number
JP6050264B2
JP6050264B2 JP2013558454A JP2013558454A JP6050264B2 JP 6050264 B2 JP6050264 B2 JP 6050264B2 JP 2013558454 A JP2013558454 A JP 2013558454A JP 2013558454 A JP2013558454 A JP 2013558454A JP 6050264 B2 JP6050264 B2 JP 6050264B2
Authority
JP
Japan
Prior art keywords
phenyl
substituted
cycloalkyl
alkyl
heterocyclyl
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.)
Active
Application number
JP2013558454A
Other languages
English (en)
Japanese (ja)
Other versions
JP2014508184A (ja
JP2014508184A5 (enExample
Inventor
ヘイセル ウルリクフ
ヘイセル ウルリクフ
ラムスベクク ダニエル
ラムスベクク ダニエル
Original Assignee
プロビオドルグ エージー
プロビオドルグ エージー
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 プロビオドルグ エージー, プロビオドルグ エージー filed Critical プロビオドルグ エージー
Publication of JP2014508184A publication Critical patent/JP2014508184A/ja
Publication of JP2014508184A5 publication Critical patent/JP2014508184A5/ja
Application granted granted Critical
Publication of JP6050264B2 publication Critical patent/JP6050264B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2026—IL-4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Psychology (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Transplantation (AREA)
  • Anesthesiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Child & Adolescent Psychology (AREA)
JP2013558454A 2011-03-16 2012-03-16 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 Active JP6050264B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161453333P 2011-03-16 2011-03-16
US61/453,333 2011-03-16
PCT/EP2012/054631 WO2012123563A1 (en) 2011-03-16 2012-03-16 Benz imidazole derivatives as inhibitors of glutaminyl cyclase

Publications (3)

Publication Number Publication Date
JP2014508184A JP2014508184A (ja) 2014-04-03
JP2014508184A5 JP2014508184A5 (enExample) 2015-05-07
JP6050264B2 true JP6050264B2 (ja) 2016-12-21

Family

ID=45852540

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2013558454A Active JP6050264B2 (ja) 2011-03-16 2012-03-16 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

Country Status (6)

Country Link
US (1) US8530670B2 (enExample)
EP (1) EP2686313B1 (enExample)
JP (1) JP6050264B2 (enExample)
DK (1) DK2686313T3 (enExample)
ES (1) ES2570167T3 (enExample)
WO (1) WO2012123563A1 (enExample)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9969734B2 (en) * 2013-07-19 2018-05-15 Syngenta Participations Ag Process for the preparation of spiroheterocyclic pyrrolidine diones
US20170363645A1 (en) 2014-12-19 2017-12-21 Probiodrug Ag Novel Method for the Detection of pGlu-Abeta Peptides
DE102015011780A1 (de) * 2015-09-16 2017-03-16 Hochschule Anhalt Neue Glutaminylcyclase-lnhibitoren
JP6928096B2 (ja) * 2017-01-10 2021-09-01 イーティーエイチ・チューリッヒ 細胞保護化合物及びそれらの使用
US10702495B2 (en) 2017-02-20 2020-07-07 Nexien Biopharma, Inc. Method and compositions for treating dystrophies and myotonia
PL3461819T3 (pl) 2017-09-29 2020-11-30 Probiodrug Ag Inhibitory cyklazy glutaminylowej
EP3521308B1 (en) 2018-01-31 2024-03-13 Vivoryon Therapeutics N.V. Humanized and de-immunized antibodies
EP3543231A1 (en) * 2018-03-19 2019-09-25 ETH Zurich Compounds for treating cns- and neurodegenerative diseases
CN108611370A (zh) * 2018-05-10 2018-10-02 江苏天瑞精准医疗科技有限公司 一种pimt表达质粒、扩增引物、构建方法及应用
EP3750528A1 (en) 2019-06-11 2020-12-16 Nexien Biopharma, Inc. Compositions for treating dystrophies and myotonia
EP4359405A4 (en) * 2021-06-24 2025-05-07 Insilico Medicine IP Limited BETA-LACTAM DERIVATIVES FOR TREATING DISEASES

Family Cites Families (551)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5736816A (ja) 1980-08-14 1982-02-27 Toshiba Corp Chodendokoirunoseizohoho
JPS57192573A (en) 1981-05-25 1982-11-26 Hochiki Co Fire fighting agent
JPS6126111A (ja) 1984-07-16 1986-02-05 Shin Meiwa Ind Co Ltd 産業用ロボツト
JPS6137764A (ja) 1984-07-31 1986-02-22 Suntory Ltd 抗プロリルエンドペプチダ−ゼ活性を有する新規生理活性化合物
US4873342A (en) 1985-04-16 1989-10-10 Suntory Limited Dipeptide derivative and synthesis and use thereof
CA1298033C (en) 1985-04-16 1992-03-24 Takaharu Tanaka Dipeptide derivative of fatty acid
JPH0623190B2 (ja) 1985-04-16 1994-03-30 サントリー株式会社 インヒビタ−活性を有するｎ−アシルピロリジン誘導体及びその製法並びに用途
JPS62114957A (ja) 1985-11-13 1987-05-26 Suntory Ltd プロリルエンドペプチダ−ゼ阻害作用を有する新規ピロリジン誘導体およびその製法並びに用途
JPH0714878B2 (ja) 1985-11-14 1995-02-22 サントリー株式会社 ピロリジンアミドを有効成分とするプロリルエンドペプチダーゼ阻害剤
JPH0764834B2 (ja) 1985-11-29 1995-07-12 サントリー株式会社 プロリルエンドペプチダーゼ阻害活性を有する新規ピロリジンアミド誘導体およびその製法並びに用途
CA1320734C (en) 1986-02-04 1993-07-27 Suntory Limited Pyrrolidineamide derivative of acylamino acid and pharmaceutical composition containing the same
US5198458A (en) 1986-02-04 1993-03-30 Suntory Limited Pyrrolidineamide derivatives of acylamino acid and pharmaceutical composition containing the same
CA1334092C (en) 1986-07-11 1995-01-24 David John Carini Angiotensin ii receptor blocking imidazoles
JPS6386485A (ja) 1986-09-30 1988-04-16 Agency Of Ind Science & Technol トンネル型ジヨセフソン接合素子
US5223482A (en) 1986-11-17 1993-06-29 Scios Nova Inc. Recombinant Alzheimer's protease inhibitory amyloid protein and method of use
JPH08806B2 (ja) 1986-11-18 1996-01-10 サントリー株式会社 プロリルエンドペプチダ−ゼ阻害作用を有する新規ピロリジンアミド誘導体
ES2058089T3 (es) 1986-11-20 1994-11-01 Ono Pharmaceutical Co Un procedimiento para la preparacion de un nuevo derivado de prolinal.
US5254550A (en) 1986-11-20 1993-10-19 Ono Pharmaceutical Co., Ltd. Prolinal derivatives and pharmaceutical compositions thereof
JPS63162672A (ja) 1986-12-25 1988-07-06 Ono Pharmaceut Co Ltd 新規なプロリナ−ル誘導体、それらの製造方法およびそれらを含有する抗健忘症剤
ES2046195T3 (es) 1986-12-29 1994-02-01 Ono Pharmaceutical Co., Ltd. Un procedimiento para la preparacion de los derivados de prolinal.
JPH089591B2 (ja) 1986-12-29 1996-01-31 小野薬品工業株式会社 新規なプロリナール誘導体
US5262431A (en) 1986-12-29 1993-11-16 Ono Pharmaceutical Co., Ltd. Prolinal derivatives and pharmaceutical compositions thereof
ES2054712T3 (es) 1987-02-04 1994-08-16 Ono Pharmaceutical Co Un procedimiento para la preparacion de los derivados de prolinal.
EP0280956B1 (en) 1987-02-23 1992-10-21 Ono Pharmaceutical Co., Ltd. Thiazolidine derivatives
JPS6442465A (en) 1987-08-07 1989-02-14 Wakunaga Pharma Co Ltd N-acylprolylpyrrolidine derivative, production and use thereof
US4857524A (en) 1987-08-08 1989-08-15 Kissei Pharmaceutical Co., Ltd. Thiazolidine compounds and therapeutic method
JP2649237B2 (ja) 1988-03-07 1997-09-03 キッセイ薬品工業 株式会社 チアゾリジン誘導体
JP2515558B2 (ja) 1987-09-10 1996-07-10 株式会社ヤクルト本社 新規なペプチドおよびそれを有効成分とする抗健忘症剤
CA1339014C (en) 1987-10-08 1997-03-25 Ronald E. Majocha Antibodies to a4 amyloid peptide
JPH0742309B2 (ja) 1987-11-30 1995-05-10 キッセイ薬品工業株式会社 チアゾリジン誘導体
JPH01250370A (ja) 1987-12-23 1989-10-05 Zeria Pharmaceut Co Ltd 新規アミノ酸イミド誘導体、製法ならびに用途
US5053414A (en) 1988-04-08 1991-10-01 Ono Pharmaceutical Co., Ltd. Heterocyclic compounds
US5328899A (en) 1988-07-15 1994-07-12 The Salk Institute For Biological Studies NPY peptide analogs
ZA896376B (en) 1988-08-26 1990-05-30 Merrell Dow Pharma Neuropeptide y agonists
ZA896374B (en) 1988-08-26 1990-05-30 Merrell Dow Pharma Neuropeptide y antagonists
JP2531989B2 (ja) 1988-09-14 1996-09-04 吉富製薬株式会社 ピリジン化合物
CA2004028C (en) 1988-12-08 1998-09-22 Motoki Torizuka Condensed benzene derivative
JPH02207070A (ja) 1989-02-07 1990-08-16 Zeria Pharmaceut Co Ltd アミノ酸イミド誘導体、それを含有する医薬及び該化合物の製造中間体
US5118811A (en) 1989-04-13 1992-06-02 Japan Tobacco Inc. Amino acid derivatives possessing prolyl endopeptidase-inhibitory activities
WO1990012870A1 (en) 1989-04-14 1990-11-01 Research Foundation For Mental Hygiene, Inc. Monoclonal antibody to amyloid peptide
WO1990012871A1 (en) 1989-04-14 1990-11-01 Research Foundation For Mental Hygiene, Inc. Cerebrovascular amyloid protein-specific monoclonal antibody sv17-6e10
SG52330A1 (en) 1989-06-14 1998-09-28 Smithkline Beecham Corp Imidazolyl-alkenoic acids
DE3939797A1 (de) 1989-12-01 1991-06-06 Basf Ag Neue vom neuropeptid y abgeleitete peptide
US4985560A (en) 1990-01-12 1991-01-15 American Home Products Corporation Pyridazino(4,5-b)indolizines
EP0443983B1 (de) 1990-02-19 1996-02-28 Ciba-Geigy Ag Acylverbindungen
JPH04211648A (ja) 1990-07-27 1992-08-03 Nippon Kayaku Co Ltd ケト酸アミド誘導体
TW201738B (enExample) 1990-03-20 1993-03-11 Sanofi Co
US4999349A (en) 1990-03-22 1991-03-12 Bristol-Myers Squibb Co. BU-4164E - A and B, prolyl endopeptidase inhibitors
US5073549A (en) 1990-03-22 1991-12-17 Bristol-Myers Squibb Company BU-4164E - A and B, prolyl endopeptidase inhibitors and their methods of use
US5196444A (en) 1990-04-27 1993-03-23 Takeda Chemical Industries, Ltd. 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof
CA2084412C (en) 1990-06-04 2000-05-09 W. Stephen Faraci Pyrrolidine and thiazolidine amides
WO1991018877A1 (en) 1990-06-07 1991-12-12 Zeria Pharmaceutical Co., Ltd. Novel arylalkanoylamine derivative and drug containing the same
US5506256A (en) 1990-07-27 1996-04-09 Yoshitomi Pharmaceutical Industries, Ltd. Proline derivatives possessing prolyl endopeptidase-inhibitory activity
JPH05186498A (ja) 1991-12-27 1993-07-27 Japan Tobacco Inc プロリン誘導体
EP0468469A2 (en) 1990-07-27 1992-01-29 Japan Tobacco Inc. Proline derivatives
CA2229000C (en) 1991-02-21 2002-04-09 Sankyo Company, Limited 1-biphenylimidazole derivatives, their preparation and their therapeutic use
US5104880A (en) 1991-05-01 1992-04-14 Mayo Foundation For Medical Education And Research Huperzine a analogs as acetylcholinesterase inhibitors
WO1992021333A2 (en) 1991-05-24 1992-12-10 Pharmavene, Inc. Treatment of drug withdrawal symptoms and drug craving with type b monoamine oxidase inhibitors
CA2089890A1 (en) 1991-06-20 1992-12-21 Makoto Yoshihama Prolyl endopeptidase inhibitors sna-115 and sna-115t, production thereof, and strain which produces said inhibitors
DE4121975A1 (de) 1991-07-03 1993-01-07 Basf Ag Thermoplastische formmassen auf der basis von polycarbonaten, styrol/acrylnitril-polymerisaten und polyolefinen
EP0597956A1 (en) 1991-07-29 1994-05-25 Warner-Lambert Company Quinazoline derivatives as acetylcholinesterase inhibitors
TW226375B (enExample) 1991-10-24 1994-07-11 American Home Prod
WO1993012139A1 (en) 1991-12-19 1993-06-24 Garvan Institute Of Medical Research A novel molecule which inhibits neuropeptide tyrosine biological function
JPH05301826A (ja) 1991-12-24 1993-11-16 Snow Brand Milk Prod Co Ltd プロリルエンドペプチダーゼ阻害剤
JPH05201970A (ja) 1992-01-24 1993-08-10 Japan Tobacco Inc 新規プロリン誘導体
JP3318622B2 (ja) 1992-05-27 2002-08-26 独立行政法人産業技術総合研究所 プロリルエンドペプチダーゼ阻害剤
GB9212308D0 (en) 1992-06-10 1992-07-22 Ici Plc Therapeutic compositions
GB9213215D0 (en) 1992-06-20 1992-08-05 Wellcome Found Peptides
JPH06116284A (ja) 1992-10-02 1994-04-26 Yamanouchi Pharmaceut Co Ltd 新規ペプチド
ES2149213T3 (es) 1992-10-05 2000-11-01 Ube Industries Compuesto de pirimidina.
US5260286A (en) 1992-10-16 1993-11-09 Japan Tobacco, Inc. 2-piperidinecarboxylic acid derivatives useful as NMDA receptor antagonists
KR0165704B1 (ko) 1992-11-20 1999-01-15 미즈노 마사루 프롤릴 엔도펩티다아제 억제 활성을 갖는 화합물 및 그 약학적 용도
US5354758A (en) 1992-12-16 1994-10-11 Japan Tobacco Inc. Benzomorphans useful as NMDA receptor antagonists
JPH06192298A (ja) 1992-12-24 1994-07-12 Mitsui Toatsu Chem Inc 新規機能性ペプチド
DE4326465A1 (de) 1993-01-20 1995-02-09 Thomae Gmbh Dr K Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
EP0683234B2 (en) 1993-01-25 2007-06-06 Takeda Chemical Industries, Ltd. Antibody against beta-amyloid or their derivative and use thereof
JPH06234693A (ja) 1993-02-09 1994-08-23 Snow Brand Milk Prod Co Ltd 新規イソテトラセノン系物質及びその製造法
FR2701480B1 (fr) 1993-02-15 1995-05-24 Sanofi Elf Composés à groupe sulfamoyle et amidino, leur procédé de préparation et les compositions pharmaceutiques les contenant.
EP0611769A1 (en) 1993-02-16 1994-08-24 Merrell Dow Pharmaceuticals Inc. Silylated acetylcholinesterase inhibitors
WO1994020476A1 (fr) 1993-03-02 1994-09-15 Fujisawa Pharmaceutical Co., Ltd. Nouveau compose heterocyclique
FR2702150B1 (fr) 1993-03-03 1995-04-07 Rhone Poulenc Rorer Sa Application de dérivés de 2H-1,2-4-benzothiadiazine-3(4H)-one-1,1-dioxyde comme antagonistes non compétitifs du récepteur NMDA.
FR2703050B1 (fr) 1993-03-24 1995-04-28 Adir Nouveaux dérivés bicycliques azotés, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
EP0627400A1 (en) 1993-06-04 1994-12-07 Merrell Dow Pharmaceuticals Inc. Aromatic acetylcholinesterase inhibitors
JPH11501281A (ja) 1993-06-18 1999-02-02 ユニバーシティ オブ シンシナティ 神経ペプチドｙアンタゴニスト及びアゴニスト
WO1995001352A1 (en) 1993-06-30 1995-01-12 Zeria Pharmaceutical Co., Ltd. Thiazolidine derivative and medicine containing the same
FR2707645B1 (fr) 1993-07-16 1995-08-11 Rhone Poulenc Rorer Sa Dérivés d'imidazo[1,2-a]pirazine-4-one, leur préparation et les médicaments les contenant.
FR2707643B1 (fr) 1993-07-16 1995-08-11 Rhone Poulenc Rorer Sa Dérivés d'imidazo[1,2-a]pyrazine-4-one, leur préparation et les médicaments les contenant.
DE69428703T2 (de) 1993-07-23 2002-05-29 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai, Tokio/Tokyo Pyrrolidin derivate
FR2711993B1 (fr) 1993-11-05 1995-12-01 Rhone Poulenc Rorer Sa Médicaments contenant des dérivés de 7H-imidazol[1,2-a]pyrazine-8-one, les nouveaux composés et leur préparation.
AU684861B2 (en) 1993-12-02 1998-01-08 Merrell Pharmaceuticals Inc. Prolyl endopeptidase inhibitors
IL111785A0 (en) 1993-12-03 1995-01-24 Ferring Bv Dp-iv inhibitors and pharmaceutical compositions containing them
FR2717813B1 (fr) 1994-03-28 1996-05-10 Rhone Poulenc Rorer Sa Dérivés d'imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one, leur préparation et les médicaments les contenant .
FR2717811B1 (fr) 1994-03-28 1996-04-26 Rhone Poulenc Rorer Sa Dérivés d'imidazo[1,2-a]pyrazine-4-one, leur préparation et les médicaments les contenant.
FR2717805B1 (fr) 1994-03-28 1996-05-10 Rhone Poulenc Rorer Sa Dérivés de 5H-indeno[1,2-b]pyrazine-2,3-dione, leur préparation et les médicaments les contenant .
FR2717812B1 (fr) 1994-03-28 1996-05-10 Rhone Poulenc Rorer Sa Indeno[1,2-e]pyrazine-4-ones, leur préparation et les médicaments les contenant.
JPH07267988A (ja) 1994-03-31 1995-10-17 Yamanouchi Pharmaceut Co Ltd 新規ペプチド
GB9410320D0 (en) 1994-05-24 1994-07-13 Fisons Corp Novel therapeutic method
GB9418443D0 (en) 1994-09-13 1994-11-02 Pfizer Ltd Therapeutic agents
WO1996012489A1 (en) 1994-10-20 1996-05-02 Eli Lilly And Company Bicyclic neuropeptide y receptor antagonists
US5663192A (en) 1994-10-20 1997-09-02 Eli Lilly And Company Heterocyclic neuropeptide Y receptor antagonists
US6562862B1 (en) 1994-10-20 2003-05-13 Eli Lilly And Company Methods of inhibiting physiological conditions associated with an excess of neuropeptide Y
FR2726275B1 (fr) 1994-11-02 1996-12-06 Rhone Poulenc Rorer Sa Spiro heterocycle-imidazo(1,2-a)indeno(1,2-e)pyrazine)-4'- ones, leur preparation et les medicaments les contenants
IL116584A0 (en) 1994-12-29 1996-03-31 Res Dev Foundation Novel flavin adenine dinucleotide analogue inhibitors of monoamine oxidase
US5691368A (en) 1995-01-11 1997-11-25 Hoechst Marion Roussel, Inc. Substituted oxazolidine calpain and/or cathepsin B inhibitors
GB9500601D0 (en) 1995-01-12 1995-03-01 Wellcome Found Modified peptides
US5786180A (en) 1995-02-14 1998-07-28 Bayer Corporation Monoclonal antibody 369.2B specific for β A4 peptide
US5552411A (en) 1995-05-26 1996-09-03 Warner-Lambert Company Sulfonylquinolines as central nervous system and cardiovascular agents
US5635503A (en) 1995-06-07 1997-06-03 Bristol-Myers Squibb Company Dihydropyridine npy antagonists: piperazine derivatives
US5554621A (en) 1995-06-07 1996-09-10 Bristol-Myers Squibb Company Dihydropyridine NPY antagonists: nitrogen heterocyclic derivatives
US5668151A (en) 1995-06-07 1997-09-16 Bristol-Myers Squibb Company Dihydropyridine NPY antagonists: piperidine derivatives
IL117997A0 (en) 1995-06-07 1996-10-31 Pfizer Neuropeptide Y1 specific ligands
JP3727383B2 (ja) 1995-07-31 2005-12-14 月桂冠株式会社 プロリルエンドペプチダーゼ阻害剤
WO1997009308A1 (en) 1995-09-01 1997-03-13 Eli Lilly And Company Indolyl neuropeptide y receptor antagonists
WO1997012613A1 (en) 1995-10-05 1997-04-10 Warner-Lambert Company Method for treating and preventing inflammation and atherosclerosis
ES2100129B1 (es) 1995-10-11 1998-02-16 Medichem Sa Nuevos compuestos aminopiridinicos policiclicos inhibidores de acetilcolinesterasa, procedimiento para su preparacion y su utilizacion.
DE19544686A1 (de) 1995-11-30 1997-06-05 Thomae Gmbh Dr K Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE19544685A1 (de) 1995-11-30 1997-06-05 Thomae Gmbh Dr K Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE19544687A1 (de) 1995-11-30 1997-06-05 Thomae Gmbh Dr K Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
AU1328197A (en) 1995-12-01 1997-06-19 Synaptic Pharmaceutical Corporation Aryl sulfonamide and sulfamide derivatives and uses thereof
WO1997020822A1 (en) 1995-12-01 1997-06-12 Novartis Ag Quinazolin-2,4-diazirines as npy receptor antagonist
AU7692996A (en) 1995-12-01 1997-06-27 Ciba-Geigy Ag Receptor antagonists
AU7626496A (en) 1995-12-01 1997-06-27 Ciba-Geigy Ag Heteroaryl compounds
WO1997020821A1 (en) 1995-12-01 1997-06-12 Novartis Ag Heteroaryl derivatives
JPH09157253A (ja) 1995-12-12 1997-06-17 Yamanouchi Pharmaceut Co Ltd 新規アミノ酸誘導体
ZA9610741B (en) 1995-12-22 1997-06-24 Warner Lambert Co 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610745B (en) 1995-12-22 1997-06-24 Warner Lambert Co 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610736B (en) 1995-12-22 1997-06-27 Warner Lambert Co 2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists
WO1997025041A1 (en) 1996-01-09 1997-07-17 Eli Lilly And Company Benzimidzolyl neuropeptide y receptor antagonists
GB9605027D0 (en) 1996-03-09 1996-05-08 Pfizer Ltd Quinoxalinediones
US5662723A (en) 1996-03-22 1997-09-02 Libbey Glass Inc. Apparatus and method for forming a decorative pattern on glassware having an edge
WO1997038993A1 (en) 1996-04-12 1997-10-23 Hoechst Marion Roussel, Inc. Isatin derivatives as acetylcholinesterase inhibitors and analgesics
DE122010000020I1 (de) 1996-04-25 2010-07-08 Prosidion Ltd Verfahren zur Senkung des Blutglukosespiegels in Säugern
WO1997046250A1 (en) 1996-06-04 1997-12-11 Synaptic Pharmaceutical Corporation Methods of modifying feeding behavior, compounds useful in such methods, and dna encoding a hypothalamic atypical neuropeptide y/peptide yy receptor (y5)
PT942751E (pt) 1996-07-05 2003-02-28 Wwk Trust The Composicoes para o tratamento de neuropatias perifericas contendo antiodepressivos e/ou inibidores da monoamino-oxidase e/ou vitamina b12 e/ou precursores ou indutores de neurotransmissores
CA2261031A1 (en) 1996-07-23 1998-01-29 Charles A. Blum Certain substituted benzylamine derivatives; a new class of neuropeptide y1 specific ligands
WO1998003493A1 (en) 1996-07-23 1998-01-29 Neurogen Corporation Certain substituted benzylamine derivatives; a new class of neuropeptide-y1 specific ligands
AU3671897A (en) 1996-07-23 1998-02-10 Neurogen Corporation Certain amido- and amino-substituted benzylamine derivatives; a new class of neuropeptite y1 specific ligands
AU3967297A (en) 1996-08-01 1998-02-25 Cocensys, Inc. Use of gaba and nmda receptor ligands for the treatment of migraine headache
US6184235B1 (en) 1996-08-14 2001-02-06 Warner-Lambert Company 2-phenyl benzimidazole derivatives as MCP-1 antagonists
WO1998007420A1 (en) 1996-08-23 1998-02-26 Agouron Acquisition Corp. Neuropeptide-y ligands
JP3880664B2 (ja) 1996-09-04 2007-02-14 月桂冠株式会社 プロリルエンドペプチダーゼ阻害ペプチド
AU4424697A (en) 1996-09-11 1998-04-02 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The The use of functional n-methyl-d-aspartate antagonists to ameliorate or prevent aminoglycoside-induced ototoxicity
WO1998015647A1 (en) 1996-10-08 1998-04-16 Novartis Ag Modulation of apoptosis
FR2754709B1 (fr) 1996-10-23 1999-03-05 Sanofi Sa Composition cosmetique contenant un antagoniste des recepteurs du neuropeptide gamma et alpha 2 antagonistes susceptibles d'etre incorpores dans une telle composition
US6011155A (en) 1996-11-07 2000-01-04 Novartis Ag N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
TW492957B (en) 1996-11-07 2002-07-01 Novartis Ag N-substituted 2-cyanopyrrolidnes
WO1998030243A1 (en) 1997-01-08 1998-07-16 Warner-Lambert Company Acetylcholinesterase inhibitors in combination with muscarinic agonists for the treatment of alzheimer's disease
US20030068316A1 (en) 1997-02-05 2003-04-10 Klein William L. Anti-ADDL antibodies and uses thereof
JP2894445B2 (ja) 1997-02-12 1999-05-24 日本たばこ産業株式会社 Ｃｅｔｐ活性阻害剤として有効な化合物
AU6417198A (en) 1997-03-13 1998-09-29 Bioresearch Ireland a division of Eolas - The Irish Science and Technology Agency Cytoprotective agents comprising monoamine oxidase inhibitors
US8173127B2 (en) 1997-04-09 2012-05-08 Intellect Neurosciences, Inc. Specific antibodies to amyloid beta peptide, pharmaceutical compositions and methods of use thereof
SI0994728T1 (sl) 1997-04-09 2009-02-28 Intellect Neurosciences Inc Rekombinantna protitelesa, specifična za beta-amiloidne konce, kodirana z DNA ter postopki za njihovo uporabo
CA2286660A1 (en) 1997-04-16 1998-10-22 Arqule, Inc. Synthesis and use of .alpha.-ketoamide derivatives and arrays
CA2289190A1 (en) 1997-05-07 1998-11-12 Algos Pharmaceutical Corporation Composition and method combining an antidepressant with an nmda receptor antagonist, for treating neuropathic pain
AU7472798A (en) 1997-05-07 1998-11-27 Algos Pharmaceutical Corporation Cox-2 inhibitors in combination with nmda-blockers for treating pain
JP3255080B2 (ja) 1997-05-28 2002-02-12 日新電機株式会社 ガス絶縁開閉装置
JP3031298B2 (ja) 1997-06-18 2000-04-10 日本電気株式会社 電流検出型センスアンプ
UA61962C2 (uk) 1997-06-30 2003-12-15 Мерц Фарма Гмбх Унд Ко. Кгаа Сполука 1-аміноалкілциклогексану, фармацевтична композиція на її основі та спосіб лікування
GB9716657D0 (en) 1997-08-07 1997-10-15 Zeneca Ltd Chemical compounds
GB9716879D0 (en) 1997-08-08 1997-10-15 Shire Int Licensing Bv Treatment of attention deficit disorders
AU7696098A (en) 1997-08-11 1999-03-01 Algos Pharmaceutical Corporation Substance p inhibitors in combination with nmda-blockers for treating pain
SE9703376D0 (sv) 1997-09-18 1997-09-18 Astra Ab A new combination
SE9703414D0 (sv) 1997-09-23 1997-09-23 Astra Ab New compounds
US7179892B2 (en) 2000-12-06 2007-02-20 Neuralab Limited Humanized antibodies that recognize beta amyloid peptide
TWI239847B (en) 1997-12-02 2005-09-21 Elan Pharm Inc N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease
US7964192B1 (en) 1997-12-02 2011-06-21 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidgenic disease
EP1052994A2 (en) 1998-02-02 2000-11-22 Trustees Of Tufts College Use of dipeptidylpetidase inhibitors to regulate glucose metabolism
EP1062222A1 (en) 1998-03-09 2000-12-27 Fondatech Benelux N.V. Serine peptidase modulators
US6007841A (en) 1998-03-13 1999-12-28 Algos Pharmaceutical Corporation Analgesic composition and method for treating pain
GB9805561D0 (en) 1998-03-16 1998-05-13 Merck Sharp & Dohme A combination of therapeutic agents
US6541208B1 (en) 1998-03-17 2003-04-01 University Of Maryland Biotechnology Institute Diagnostic method for distinguishing HIV-associated dementia from other forms of dementia
DE19812331A1 (de) 1998-03-20 1999-09-23 Merck Patent Gmbh Piperidinderivate
US6054451A (en) 1998-04-21 2000-04-25 Algos Pharmaceutical Corporation Analgesic composition and method for alleviating pain
AU3879899A (en) 1998-05-04 1999-11-23 Neotherapeutics, Inc. Novel dopamine-like 9-substituted hypoxanthine and methods of use
US6303617B1 (en) 1998-05-04 2001-10-16 Neotherapeutics, Inc. Serotonin-like 9-substituted hypoxanthine and methods of use
ES2345746T3 (es) 1998-05-21 2010-09-30 University Of Tennessee Research Foundation Metodos para la eliminacion de amiloide usando anticuerpos antiamiloide.
DE19823831A1 (de) 1998-05-28 1999-12-02 Probiodrug Ges Fuer Arzneim Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen
DE19828113A1 (de) 1998-06-24 2000-01-05 Probiodrug Ges Fuer Arzneim Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV
DE19828114A1 (de) 1998-06-24 2000-01-27 Probiodrug Ges Fuer Arzneim Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV
PE20000728A1 (es) 1998-06-26 2000-08-21 Cocensys Inc Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda
US6262081B1 (en) 1998-07-10 2001-07-17 Dupont Pharmaceuticals Company Composition for and method of treating neurological disorders
DE19834591A1 (de) 1998-07-31 2000-02-03 Probiodrug Ges Fuer Arzneim Verfahren zur Steigerung des Blutglukosespiegels in Säugern
AU5027299A (en) 1998-07-31 2000-02-28 Novo Nordisk A/S Use of glp-1 and analogues for preventing type ii diabetes
JP4009367B2 (ja) 1998-08-04 2007-11-14 株式会社ディスコ スピン洗浄・乾燥方法
US6218383B1 (en) 1998-08-07 2001-04-17 Targacept, Inc. Pharmaceutical compositions for the prevention and treatment of central nervous system disorders
IL125809A (en) 1998-08-17 2005-08-31 Finetech Lab Ltd Process and intermediates for production of donepezil and related compounds
JP4208299B2 (ja) 1998-08-19 2009-01-14 東レ株式会社 金属板貼合わせ成形加工用ポリエステルフィルム
IT1304904B1 (it) 1998-09-11 2001-04-05 Eisai Co Ltd Derivati anticolinesterasici per il trattamento delle sindromidolorose funzionali e/o organiche
AU6472799A (en) 1998-10-16 2000-05-08 Janssen Pharmaceutica N.V. Therapy for improving cognition
EP1146905A1 (en) 1998-11-12 2001-10-24 Algos Pharmaceutical Corporation Cox-2 inhibitors in combination with nmda-blockers for treating pain
WO2000030446A1 (en) 1998-11-23 2000-06-02 Bonnie Davis Dosage formulations for acetylcholinesterase inhibitors
WO2000030674A1 (en) 1998-11-26 2000-06-02 Ferring Bv Neuropeptide y y4 agents in the treatment of reproductive disorders
CA2354035A1 (en) 1998-12-11 2000-06-15 Bonnie Davis Use of acetylcholinesterase inhibitors on the modulation of the hypothalamic-pituitary-gonadal axis
GB9902461D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB9902459D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB9902452D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB9902453D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB9902455D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
AU3195600A (en) 1999-03-23 2000-10-09 Sumitomo Pharmaceuticals Company, Limited Tricyclic indole-2-carboxylic acid compound used as nmda receptor antagonist
CA2363984A1 (en) 1999-04-15 2000-10-26 Merck Frosst Canada & Co. Antibodies that recognize app cleaved by caspases and methods of use
US6121311A (en) 1999-04-28 2000-09-19 Japan Tobacco Inc. Method for treating cocainism
EP1177172A1 (en) 1999-05-05 2002-02-06 Ortho-McNeil Pharmaceutical, Inc. 3a,4,5,9b-TETRAHYDRO-1H-BENZ e]INDOL-2-YL AMINE-DERIVED NEUROPEPTIDE Y RECEPTORS LIGANDS USEFUL IN THE TREATMENT OF OBESITY AND OTHER DISORDERS
JP3148739B2 (ja) 1999-05-19 2001-03-26 ドーマー株式会社 プロリルエンドペプチダーゼ阻害剤
JP3056486B1 (ja) 1999-06-15 2000-06-26 株式会社東京機械製作所 印刷機用インキレ―ル
JP5249482B2 (ja) 1999-06-16 2013-07-31 ボストン・バイオメデイカル・リサーチ・インステイテユート インビボのβ−アミロイドレベルの免疫学的制御
US6107317A (en) 1999-06-24 2000-08-22 Novartis Ag N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6172081B1 (en) 1999-06-24 2001-01-09 Novartis Ag Tetrahydroisoquinoline 3-carboxamide derivatives
US6110949A (en) 1999-06-24 2000-08-29 Novartis Ag N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6524616B1 (en) 1999-06-25 2003-02-25 Wake Forest University Health Services Compositions and methods for treating or preventing neurodegeneration and cognitive decline and dysfunction associated with alzheimer's disease, aging, other dementia related disorders and estrogen deficiency related conditions
DE19936719A1 (de) 1999-08-06 2001-02-15 Gruenenthal Gmbh Substituierte 1,5-Dihydropyrrol-2-on-Derivate
DE19936521A1 (de) 1999-08-06 2001-02-15 Gruenenthal Gmbh Substituierte Pyrrolidin-2,3,4-trion-3-oxim-Derivate
JP2003507013A (ja) 1999-08-13 2003-02-25 ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク βシートフィブリルのＲＡＧＥへの結合を阻害する方法及びその結果
EP1078632A1 (en) 1999-08-16 2001-02-28 Sanofi-Synthelabo Use of monoamine oxydase inhibitors for the manufacture of drugs intended for the treatment of obesity
DE19940130A1 (de) 1999-08-24 2001-03-01 Probiodrug Ges Fuer Arzneim Neue Effektoren der Dipeptidyl Peptidase IV zur topischen Anwendung
TWI283577B (en) 1999-10-11 2007-07-11 Sod Conseils Rech Applic Pharmaceutical composition of imidazole derivatives acting as modulators of sodium channels and the use thereof
UA72558C2 (uk) 1999-11-01 2005-03-15 Мерц Фарма Гмбх Унд Ко. Кгаа 1-аміноалкілциклогексанові антагоністи рецептора nmda
EP1228061A4 (en) 1999-11-12 2004-12-15 Guilford Pharm Inc DIPEPTIDYL PEPTIDASE IV INHIBITORS; METHODS OF MANUFACTURE AND USE OF SAID INHIBITORS
GB9928330D0 (en) 1999-11-30 2000-01-26 Ferring Bv Novel antidiabetic agents
WO2001055105A1 (en) 2000-01-24 2001-08-02 Novo Nordisk A/S N-substituted 2-cyanopyroles and -pyrrolines which are inhibitors of the enzyme dpp-iv
AU779875B2 (en) 2000-01-24 2005-02-17 Merck Sharp & Dohme Limited Gamma-secretase inhibitors
EA006606B1 (ru) 2000-02-24 2006-02-24 Вашингтон Юниверсити Гуманизированное антитело и его фрагмент, взаимодействующие с бета-амилоидным пептидом, и способы их применения
GB0005251D0 (en) 2000-03-03 2000-04-26 Merck Sharp & Dohme Therapeutic compounds
AU2001239052A1 (en) 2000-03-06 2001-09-17 Immune Network Ltd. Compositions for prevention and treatment of dementia
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
US6992081B2 (en) 2000-03-23 2006-01-31 Elan Pharmaceuticals, Inc. Compounds to treat Alzheimer's disease
AU2001252958A1 (en) 2000-03-23 2001-10-03 Elan Pharmaceuticals, Inc. Compounds and methods to treat alzheimer's disease
GB0008710D0 (en) 2000-04-07 2000-05-31 Merck Sharp & Dohme Therapeutic compounds
EP1285656A4 (en) 2000-04-13 2006-07-12 Eisai Co Ltd ACETYLCHOLINESTERASE HEMMER CONTAINING 1-BENZYLPYRIDINIUM SALT
MXPA02009659A (es) 2000-04-26 2003-03-10 Warner Lambert Co Derivado de ciclohexilamina como subtipo de los antagonistas del receptor selectivo nmda.
GB0010183D0 (en) 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
GB0010188D0 (en) 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
US20010036949A1 (en) 2000-05-09 2001-11-01 Coe Jotham Wadsworth Pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal
MXPA02010863A (es) 2000-06-01 2003-03-27 Warner Lambert Co Derivados de ciclohexilamina como subtipo de antagonistas del receptor nmda selectivo.
ATE301642T1 (de) 2000-06-06 2005-08-15 Warner Lambert Co Bicyclische cyclohexylamine und ihre verwendung als nmda-rezeptor antagonisten
GB0015488D0 (en) 2000-06-23 2000-08-16 Merck Sharp & Dohme Therapeutic agents
US6713276B2 (en) 2000-06-28 2004-03-30 Scios, Inc. Modulation of Aβ levels by β-secretase BACE2
US6686449B2 (en) 2000-06-30 2004-02-03 Pharmacia & Upjohn Company Mutant presenilin 1 polypeptides
CA2410680A1 (en) 2000-06-30 2002-01-10 Elan Pharmaceuticals, Inc. Compounds to treat alzheimer's disease
MXPA02012272A (es) 2000-07-04 2003-04-25 Novo Nordisk As Compuestos heterociclicos que son inhibidores de la enzima dipeptidilpeptidasa-iv.
GB0016681D0 (en) 2000-07-06 2000-08-23 Merck Sharp & Dohme Therapeutic compounds
US6556971B1 (en) 2000-09-01 2003-04-29 Snap-On Technologies, Inc. Computer-implemented speech recognition system training
US20040236450A1 (en) 2000-09-25 2004-11-25 Motorwiz, Inc. Model-based machine diagnostics and prognostics using theory of noise and communications
US20020151591A1 (en) 2000-10-17 2002-10-17 Anabella Villalobos Combination use of acetylcholinesterase inhibitors and GABAa inverse agonists for the treatment of cognitive disorders
HU227197B1 (en) 2000-10-24 2010-10-28 Richter Gedeon Nyrt Nmda receptor antagonist carboxylic acid amide derivatives and pharmaceutical compositions containing them
DE60112957T2 (de) 2000-11-02 2006-05-18 Merck Sharp & Dohme Ltd., Hoddesdon Sulfamide als gamma-secretase-inhibitoren
WO2002041842A2 (en) 2000-11-03 2002-05-30 Proteotech. Inc. Antibody pti-hs7 for treatment of alzheimer's disease and other amyloidoses and parkinson's disease
TWI243162B (en) 2000-11-10 2005-11-11 Taisho Pharmaceutical Co Ltd Cyanopyrrolidine derivatives
PE20020574A1 (es) 2000-12-06 2002-07-02 Wyeth Corp Anticuerpos humanizados que reconocen el peptido amiloideo beta
US6495335B2 (en) 2000-12-07 2002-12-17 Mario Chojkier Compositions and methods for diagnosing alzheimer's disease
US6670364B2 (en) 2001-01-31 2003-12-30 Telik, Inc. Antagonists of MCP-1 function and methods of use thereof
TWI245761B (en) 2001-03-01 2005-12-21 Telik Inc Antagonists of MCP-1 function and methods of use thereof
JP2005506292A (ja) 2001-03-08 2005-03-03 エモリー　ユニバーシティ ｐＨに依存するＮＭＤＡレセプターアンタゴニスト
US6649196B2 (en) 2001-03-12 2003-11-18 Mayo Foundation For Medical Education And Research Methods of reducing β-amyloid polypeptides
US6815175B2 (en) 2001-03-16 2004-11-09 Cornell Research Foundation, Inc. Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder
TWI236474B (en) 2001-04-03 2005-07-21 Telik Inc Antagonists of MCP-1 function and methods of use thereof
US6573287B2 (en) 2001-04-12 2003-06-03 Bristo-Myers Squibb Company 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase IV and method
AU2002258808A1 (en) 2001-04-30 2002-11-11 Eli Lilly And Company Humanized antibodies
ATE409047T1 (de) 2001-04-30 2008-10-15 Lilly Co Eli Humanisierte antikörper
FR2824825B1 (fr) 2001-05-15 2005-05-06 Servier Lab Nouveaux derives d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
SI20922A (sl) 2001-05-18 2002-12-31 Krka Tovarna Zdravil, D.D., Novo Mesto Monoklonsko protitelo, ki nevtralizira aktivnost katepsina B, in njegove uporabe
US20030013177A1 (en) 2001-05-23 2003-01-16 Ebens Allen J. Polynucleotides encoding insect glutaminyl cyclase and uses thereof
US6562783B2 (en) 2001-05-30 2003-05-13 Neurologic, Inc. Phosphinylmethyl and phosphorylmethyl succinic and glutauric acid analogs as β-secretase inhibitors
ATE396174T1 (de) 2001-06-01 2008-06-15 Elan Pharm Inc Hydroxyalkylaminderivate als beta-secretase- inhibitoren und deren verwendung zur behandlung der alzheimerschen krankheit oder ähnlicher krankheiten
AU2002344820B2 (en) 2001-06-20 2006-12-14 Merck & Co., Inc. Dipeptidyl peptidase inhibitors for the treatment of diabetes
CA2450475A1 (en) 2001-06-20 2003-01-03 Linda Brockunier Dipeptidyl peptidase inhibitors for the treatment of diabetes
GB0115517D0 (en) 2001-06-25 2001-08-15 Ferring Bv Novel antidiabetic agents
WO2003072556A1 (en) 2001-06-27 2003-09-04 Prosidion Ltd. Glutaminyl based dpiv inhibitors
CA2452039A1 (en) 2001-06-27 2003-01-09 Elan Pharmaceuticals, Inc. Beta-hydroxyamine derivatives useful in treatment of alzheimer's disease
JP3909056B2 (ja) 2001-06-27 2007-04-25 スミスクライン ビーチャム コーポレーション ジペプチジルペプチダーゼ阻害剤としてのフルオロピロリジン類
RU2299066C2 (ru) 2001-06-27 2007-05-20 Пробиодруг Аг Новые ингибиторы дипептидилпептидазы iv и их применение в качестве противораковых агентов
DE10150203A1 (de) 2001-10-12 2003-04-17 Probiodrug Ag Peptidylketone als Inhibitoren der DPIV
DE10154689A1 (de) 2001-11-09 2003-05-22 Probiodrug Ag Substituierte Aminoketonverbindungen
ATE370943T1 (de) 2001-06-27 2007-09-15 Smithkline Beecham Corp Fluoropyrrolidine als dipeptidyl-peptidase inhibitoren
ATE380175T1 (de) 2001-06-27 2007-12-15 Smithkline Beecham Corp Pyrrolidine als dipeptidyl peptidase inhibitoren
EP1404675B1 (en) 2001-07-03 2008-03-12 Novo Nordisk A/S Dpp-iv-inhibiting purine derivatives for the treatment of diabetes
UA74912C2 (en) 2001-07-06 2006-02-15 Merck & Co Inc Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes
KR100890676B1 (ko) 2001-07-24 2009-03-26 리히데 게데온 베기에스제티 기아르 알티 신규한 카르복시산 아미드 화합물
WO2003012141A1 (en) 2001-07-31 2003-02-13 Takeda Chemical Industries, Ltd. Method of screening alzheimer’s disease-associated gene
EP1420032B2 (en) 2001-08-03 2015-12-16 Medical & Biological Laboratories Co., Ltd. Antibody recognizing gm1 ganglioside-bound amyloid beta-protein and dna encoding the antibody
MXPA04001014A (es) 2001-08-03 2004-05-27 Schering Corp Novedosos inhibidores de la gama secretasa.
US7122675B2 (en) 2001-08-03 2006-10-17 Schering Corporation Gamma secretase inhibitors
WO2003016466A2 (en) 2001-08-17 2003-02-27 Eli Lilly And Company ANTI-Aβ ANTIBODIES
EP1519740A4 (en) 2001-08-17 2005-11-09 Lilly Co Eli FASTER IMPROVEMENT OF COGNITION IN DISEASES ASSOCIATED WITH A-BETA
CA2459146A1 (en) 2001-08-30 2003-03-13 Ortho-Mcneil Pharmaceutical, Inc. Treatment of dementia and memory disorders with anticonvulsants and acetylcholinesterase inhibitors
TWI246510B (en) 2001-09-14 2006-01-01 Mitsubishi Pharma Corp Thiazolidine derivatives and pharmaceutical uses thereof
AU2002331311A1 (en) 2001-09-19 2003-04-01 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme dpp-iv
GB0125446D0 (en) 2001-10-23 2001-12-12 Ferring Bv Novel anti-diabetic agents
EP1448218A4 (en) 2001-10-23 2009-01-14 Oklahoma Med Res Found BETA SECRETASE INHIBITORS AND METHOD OF USE
GB0125445D0 (en) 2001-10-23 2001-12-12 Ferring Bv Protease Inhibitors
US6861440B2 (en) 2001-10-26 2005-03-01 Hoffmann-La Roche Inc. DPP IV inhibitors
EP1447095B1 (en) 2001-11-02 2012-06-13 Kensuke Egashira Preventives and/or remedies for post-transplant arteriosclerosis as rejection of organ transplant
US7060270B2 (en) 2001-11-02 2006-06-13 Diagenics International Corporation Methods and compositions of monoclonal antibodies specific for beta-amyloid proteins
US20050208050A1 (en) 2001-11-09 2005-09-22 Gerd Multhaup Compounds for the diagnosis/prevention/treatment of alzheimer's disease
BR0214295A (pt) 2001-11-19 2004-11-09 Elan Pharm Inc Composto, método para tratar um paciente que tem ou prevenir um paciente de adquirir uma doença ou condição, e, método para produzir um composto
EP1572894B1 (en) 2001-11-21 2016-04-13 New York University Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto
JP4771661B2 (ja) 2001-11-26 2011-09-14 トラスティーズ オブ タフツ カレッジ Ｐｏｓｔ−プロリン開裂酵素の擬ペプチド性阻害剤
AU2002354433A1 (en) 2001-12-06 2003-06-17 Japan As Represented By Secretary Of Chubu National Hospital Alzheimer's disease-associated gene and protein and use thereof
US20050227941A1 (en) 2001-12-17 2005-10-13 Karen Duff Sequestration of ass in the periphery in the absence of immunomodulating agent as a therapeutic approach for the treatment or prevention of beta-amyloid related diseases
CN1596240A (zh) 2001-12-19 2005-03-16 阿特罗吉尼克斯公司 查耳酮衍生物及其治疗疾病的用途
US20060210555A1 (en) 2001-12-21 2006-09-21 Antigenics, Inc. Compositions comprising immunoreactive reagents and saponins, and methods of use thereof
WO2003057144A2 (en) 2001-12-26 2003-07-17 Guilford Pharmaceuticals Change inhibitors of dipeptidyl peptidase iv
US6727261B2 (en) 2001-12-27 2004-04-27 Hoffman-La Roche Inc. Pyrido[2,1-A]Isoquinoline derivatives
WO2003057204A2 (en) 2002-01-08 2003-07-17 Nordic Bioscience A/S Modulation of iamt (pimt or pcmt) in immune system
AU2003205630A1 (en) 2002-01-18 2003-07-30 The Genetics Company Inc. Beta-secretase inhibitors
AU2003207973A1 (en) 2002-01-31 2003-09-02 Tel Aviv University Future Technology Development L.P. Peptides antibodies directed thereagainst and methods using same for diagnosing and treating amyloid-associated diseases
TW200302717A (en) 2002-02-06 2003-08-16 Schering Corp Novel gamma secretase inhibitors
US20040171614A1 (en) 2002-02-06 2004-09-02 Schering-Plough Corporation Novel gamma secretase inhibitors
CN1324015C (zh) 2002-02-13 2007-07-04 霍夫曼-拉罗奇有限公司 吡啶－和嘧啶－衍生物
PL372488A1 (en) 2002-02-13 2005-07-25 F.Hoffmann-La Roche Ag Novel pyridine- and quinoline-derivatives
AR038568A1 (es) 2002-02-20 2005-01-19 Hoffmann La Roche Anticuerpos anti-a beta y su uso
HUP0200849A2 (hu) 2002-03-06 2004-08-30 Sanofi-Synthelabo N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra
MY139983A (en) 2002-03-12 2009-11-30 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
EP1490335B1 (en) 2002-03-25 2007-09-19 Merck & Co., Inc. Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
ES2297141T3 (es) 2002-03-29 2008-05-01 EISAI R&D MANAGEMENT CO., LTD. Derivados de (1-indanona)-(1,2,3,6-tetrahidropiridina).
US20070134247A9 (en) 2002-04-12 2007-06-14 Ramot At Tel Aviv University Ltd. Prevention of brain inflammation as a result of induced autoimmune response
KR100994748B1 (ko) 2002-04-19 2010-11-17 더 가버닝 카운실 오브 더 유니버시티 오브 토론토 알쯔하이머병의 치료를 위한 면역학적 방법 및 조성물
DE60329995D1 (de) 2002-04-24 2009-12-24 Hiroshi Mori Gamma-sekretase-inhibitoren
DE60324544D1 (de) 2002-04-26 2008-12-18 Schering Corp Muskarin antagonisten
US7205336B2 (en) 2002-05-17 2007-04-17 Merck & Co., Inc. β-secretase inhibitors
EP1509232B1 (en) 2002-05-31 2008-11-19 H. Lundbeck A/S A combination of an nmda-antagonist and acetylcholine esterase inhibitors for the treatment of alzheimer's disease
JP2005533771A (ja) 2002-06-04 2005-11-10 ファイザー・プロダクツ・インク ジペプチジルペプチダーゼｉｖ阻害剤としてのフッ素化環式アミド
WO2003101449A2 (en) 2002-06-04 2003-12-11 Pfizer Products Inc. Process for the preparation of 3,3,4,4-tetrafluoropyrrolidine and derivatives thereof
CA2485641C (en) 2002-06-06 2010-12-14 Eisai Co., Ltd. Novel condensed imidazole derivatives
AU2003279355A1 (en) 2002-06-19 2004-01-06 Surface Specialties, S.A. Semi-gloss powder coating compositions
AU2003248259A1 (en) 2002-07-10 2004-02-02 Yamanouchi Pharmaceutical Co., Ltd. Novel azetidine derivative or salt thereof
WO2004007468A1 (en) 2002-07-15 2004-01-22 Merck & Co., Inc. Piperidino pyrimidine dipeptidyl peptidase inhibitors for the treatment of diabetes
US20040019118A1 (en) 2002-07-19 2004-01-29 Khalid Iqbal NMDA receptor antagonists and their use in inhibiting abnormal hyperphosphorylation of microtubule associated protein tau
US7557137B2 (en) 2002-08-05 2009-07-07 Bristol-Myers Squibb Company Gamma-lactams as beta-secretase inhibitors
CA2496249C (en) 2002-08-21 2012-01-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments
DE10238477A1 (de) 2002-08-22 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Purinderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE10238470A1 (de) 2002-08-22 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
WO2005025516A2 (en) 2003-09-12 2005-03-24 The Regents Of The University Of California Monoclonal antibodies specific for conformational epitopes of prefibrillar aggregates
ES2201929B1 (es) 2002-09-12 2005-05-16 Araclon Biotech, S.L. Anticuerpos policlonales, metodo de preparacion y uso de los mismos.
DE60336848D1 (de) 2002-09-12 2011-06-01 Univ California Immunogene und entsprechende antikörper, die spezifisch sind für häufige hochmolekulare aggregations-zwischenprodukte von amyloiden aus proteinen unterschiedlicher sequenz
CA2497804A1 (en) 2002-09-12 2004-03-25 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Human anti-human mcp-1 antibody and fragment of said antibody
DK1560811T3 (da) 2002-09-19 2007-12-10 Abbott Lab Farmaceutiske sammensætninger som inhibitorer af dipeptidylpeptidase-IV (DPP-IV)
AU2003282804A1 (en) 2002-09-20 2004-04-08 Axys Pharmaceuticals, Inc. 3-(3,5-disubstituted-4-hydroxyphenyl)propionamide derivatives as cathepsin b inhibitors
US7273889B2 (en) 2002-09-25 2007-09-25 Innovative Drug Delivery Systems, Inc. NMDA receptor antagonist formulation with reduced neurotoxicity
WO2004029629A1 (en) 2002-09-27 2004-04-08 Janssen Pharmaceutica N.V. N-11 truncated amyloid-beta nomoclonal antibodies, compositions, methods and uses
JP2006508072A (ja) 2002-10-01 2006-03-09 ノースウエスタン ユニバーシティ アミロイドベータ由来拡散性リガンド（ＡＤＤＬｓ）、ＡＤＤＬ代替物、ＡＤＤＬ結合性分子、およびそれらの使用
GB0223038D0 (en) 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
GB0223039D0 (en) 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
WO2004032836A2 (en) 2002-10-07 2004-04-22 Merck & Co., Inc. Antidiabetic beta-amino heterocylcic dipeptidyl peptidase inhibitors
WO2004033455A2 (en) 2002-10-08 2004-04-22 Novo Nordisk A/S Hemisuccinate salts of heterocyclic dpp-iv inhibitors
AU2003279216A1 (en) 2002-10-09 2004-05-04 Rinat Neuroscience Corp. Methods of treating alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof
GB0223494D0 (en) 2002-10-09 2002-11-13 Neuropharma Sa Dual binding site acetylcholinesterase inhibitors for the treatment of alzheimer's disease
HRP20050343A2 (en) 2002-10-18 2007-03-31 Merck & Co. Inc. Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
CN100339070C (zh) 2002-10-24 2007-09-26 莫茨药物股份两合公司 包含1－氨基环己烷衍生物类和乙酰胆碱酯酶抑制剂类的药物组合物
US20040082543A1 (en) 2002-10-29 2004-04-29 Pharmacia Corporation Compositions of cyclooxygenase-2 selective inhibitors and NMDA receptor antagonists for the treatment or prevention of neuropathic pain
WO2004041795A1 (en) 2002-10-30 2004-05-21 Guilford Pharmaceuticals Inc. Novel inhibitors of dipeptidyl peptidase iv
AU2003285296A1 (en) 2002-10-30 2004-05-25 Nordic Bioscience A/S Coumpounds modulating the activity of gapdh and/or iamt
GB0225474D0 (en) 2002-11-01 2002-12-11 Merck Sharp & Dohme Therapeutic agents
FR2846667B1 (fr) 2002-11-06 2004-12-31 Pasteur Institut Fragments variables d'anticorps de camelides a chaine unique diriges contre le peptide beta-amyloide 1-42 et leurs applications pour le diagnostic et le traitement des maladies neuroagregatives
JP4413863B2 (ja) 2002-11-07 2010-02-10 メルク エンド カムパニー インコーポレーテッド 糖尿病の治療又は予防のためのジペチジルペプチダーゼ阻害剤としてのフェニルアラニン誘導体
DE60329316D1 (de) 2002-11-12 2009-10-29 Merck & Co Inc Phenylcarboxamide als beta-sekretase-hemmer zur behandlung von alzheimer
AU2002952946A0 (en) 2002-11-27 2002-12-12 Fujisawa Pharmaceutical Co., Ltd. Dpp-iv inhibitor
JP2006510630A (ja) 2002-12-04 2006-03-30 メルク　エンド　カムパニー　インコーポレーテッド 糖尿病を治療又は予防するためのジペプチジルペプチダーゼ阻害剤としてのフェニルアラニン誘導体
US7420079B2 (en) 2002-12-09 2008-09-02 Bristol-Myers Squibb Company Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof
WO2004056727A2 (en) 2002-12-19 2004-07-08 Atherogenics, Inc. Process of making chalcone derivatives
EP1583534A4 (en) 2002-12-20 2007-08-29 Merck & Co Inc 3-AMINO-4-PHENYLBUTANIC ACID DERIVATIVES AS DIPEPTIDYL-PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
EP1583750B1 (en) 2003-01-07 2013-02-27 Merck Sharp & Dohme Corp. Macrocyclic beta-secretase inhibitors for treatment of Alzheimer's disease
CA2512546A1 (en) 2003-01-17 2004-08-05 Merck & Co., Inc. 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
DE10303974A1 (de) 2003-01-31 2004-08-05 Abbott Gmbh & Co. Kg Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung
JP2006516573A (ja) 2003-01-31 2006-07-06 メルク　エンド　カムパニー　インコーポレーテッド 糖尿病の治療および予防のためのジペプチジルペプチダーゼ阻害薬としての３−アミノ−４−フェニルブタン酸誘導体
KR20050118669A (ko) 2003-02-01 2005-12-19 뉴랄랩 리미티드 가용성 ａ-베타에 대한 항체를 생성하기 위한 능동 면역화
CN100480248C (zh) 2003-02-04 2009-04-22 弗·哈夫曼-拉罗切有限公司 用作γ-分泌酶抑制剂的丙二酰胺衍生物
ES2344645T3 (es) 2003-02-10 2010-09-02 Applied Molecular Evolution, Inc. Moleculas de union al abeta.
WO2004071454A2 (en) 2003-02-13 2004-08-26 Guilford Pharmaceuticals Inc. Substituted azetidine compounds as inhibitors of dipeptidyl peptidase iv
CA2516259A1 (en) 2003-02-18 2004-09-02 Roskamp Research, Llc Anti-angiogenic and anti-tumoral properties of beta and gamma secretase inhibitors
US8663650B2 (en) 2003-02-21 2014-03-04 Ac Immune Sa Methods and compositions comprising supramolecular constructs
WO2004076434A1 (en) 2003-02-28 2004-09-10 Aic Dipeptidyl peptidase inhibitors
WO2004076433A1 (en) 2003-02-28 2004-09-10 Aic Dipeptidyl peptidase inhibitors
EP1454627A1 (en) 2003-03-06 2004-09-08 MyoContract Ltd. Alpha-Keto carbonyl calpain inhibitors
WO2004084830A2 (en) 2003-03-21 2004-10-07 Buck Institute Method for treating alzheimer’s dementia
US20040191334A1 (en) 2003-03-24 2004-09-30 Pang-Chui Shaw Use of transhinone derivates as cholinesterase inhibitors in treating related diseases
US20040242568A1 (en) 2003-03-25 2004-12-02 Syrrx, Inc. Dipeptidyl peptidase inhibitors
CN1777425A (zh) 2003-03-28 2006-05-24 阿卡蒂亚药品公司 用于疼痛控制的毒蕈碱性m1受体激动剂
CA2520853A1 (en) 2003-03-28 2005-03-31 Centocor, Inc. Anti-amyloid antibodies, compositions, methods and uses
WO2004092189A1 (en) 2003-04-09 2004-10-28 Wyeth Derivatives of 2-(8,9-dioxo-2,6-diazabicyclo(5.2.0)non-1(7)-en-2-yl)alkyl phosphonic acid and their use as n-methyl-d-aspartate (nmda) recetor antagonists
GB0308318D0 (en) 2003-04-10 2003-05-14 Merck Sharp & Dohme Therapeutic agents
GB0308382D0 (en) 2003-04-10 2003-05-21 Univ Cambridge Tech Therapeutic methods and means
WO2004089362A1 (en) 2003-04-11 2004-10-21 Novo Nordisk A/S 2-cyanopyrroles and their analogues as ddp-iv inhibitors
PL1620082T3 (pl) 2003-05-05 2010-10-29 Probiodrug Ag Medyczne zastosowanie inhibitorów cyklazy glutaminylowej i glutaminianowej do leczenia choroby Alzheimera i zespołu Downa
EP1620091B1 (en) 2003-05-05 2010-03-31 Probiodrug AG Inhibitors of glutaminyl cyclase
EP1622870A2 (en) 2003-05-05 2006-02-08 Prosidion Ltd. Glutaminyl based dp iv-inhibitors
ES2246177B1 (es) 2003-05-08 2007-03-01 Universidad De Zaragoza. Uso de anticuerpos para el tratamiento de enfermedades amiloideas.
AU2003902260A0 (en) 2003-05-09 2003-05-29 Fujisawa Pharmaceutical Co., Ltd. Dpp-iv inhibitor
TW200510405A (en) 2003-05-13 2005-03-16 Schering Corp Bridged n-arylsulfonylpiperidines as gamma-secretase inhibitors
WO2004103276A2 (en) 2003-05-14 2004-12-02 Merck & Co., Inc. 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
JP2007511467A (ja) 2003-05-14 2007-05-10 タケダ サン ディエゴ インコーポレイテッド ジペプチジルペプチダーゼインヒビター
KR20060013404A (ko) 2003-05-16 2006-02-09 머크 샤프 앤드 돔 리미티드 γ-세크레타제 억제용 사이클릭 설폰아미드
UA80055C2 (en) 2003-05-27 2007-08-10 Forest Laboratories Combination of nmda-receptor antagonist and selective inhibitor of serotonin reuptake for a depression and other pscihiatric disorders treatment
TWI306458B (en) 2003-05-30 2009-02-21 Elan Pharma Int Ltd Humanized antibodies that recognize beta amyloid peptide
AU2003902828A0 (en) 2003-06-05 2003-06-26 Fujisawa Pharmaceutical Co., Ltd. Dpp-iv inhibitor
WO2004110436A1 (en) 2003-06-06 2004-12-23 Merck & Co., Inc. Fused indoles as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
AU2003902946A0 (en) 2003-06-12 2003-06-26 Fujisawa Pharmaceutical Co., Ltd. Dpp-iv inhibitor
US7456204B2 (en) 2003-06-17 2008-11-25 Merck & Co., Inc. Cyclohexylglycine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
MXPA05013904A (es) 2003-06-20 2006-02-24 Hoffmann La Roche Derivados de pirido[2,1-a] isoquinolinas como inhibidores de dipeptidil-peptidasa iv(dpp-iv).
ATE437876T1 (de) 2003-06-20 2009-08-15 Hoffmann La Roche Hexahydropyridoisochinoline als dpp-iv- inhibitoren
JP2007516207A (ja) 2003-06-30 2007-06-21 メルク　エンド　カムパニー　インコーポレーテッド アルツハイマー病の治療のためのＮ−アルキルフェニルカルボキサミドβ−セクレターゼ阻害剤
CN101415724B (zh) 2003-06-30 2015-12-02 特拉维夫大学未来科技开发有限公司 肽、抗肽抗体以及用它们来诊断和治疗淀粉样蛋白相关疾病的方法
JP2007522088A (ja) 2003-07-01 2007-08-09 メルク　エンド　カムパニー　インコーポレーテッド アルツハイマー病の治療用フェニルカルボン酸ベータセクレターゼ阻害剤
WO2005007614A1 (en) 2003-07-03 2005-01-27 The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services 6011 Monoamine oxidase inhibitors
AU2004257367A1 (en) 2003-07-16 2005-01-27 Resverlogix, Inc. Compounds and methods for downregulating the effects of TGF-beta
WO2005008250A1 (en) 2003-07-21 2005-01-27 Angiogenetics Sweden Ab Compounds and methods for promoting angiogenesis by using a gamma-secretase inhibitor or inhibiting the gamma-secretase pathway
EP1660058A2 (en) 2003-07-28 2006-05-31 Merz Pharma GmbH & Co. KGaA The use of 1-amino-alkylcyclohexane compounds in the treatment of pain hypersensitivity
CN1882551A (zh) 2003-07-31 2006-12-20 麦克公司 用作用于治疗或预防糖尿病的二肽基肽酶－iv酶抑制剂的六氢二氮杂吖庚因酮
US20050124016A1 (en) 2003-08-01 2005-06-09 Enh Research Institute Antibodies specific for toxic amyloid beta protein oligomers
GB0318447D0 (en) 2003-08-05 2003-09-10 Merck Sharp & Dohme Therapeutic agents
MXPA06001601A (es) 2003-08-13 2006-08-25 Takeda Pharmaceutical Derivados de 4-pirimidona y su uso como inhibidores de dipeptidilpeptidasa.
JP2007502278A (ja) 2003-08-14 2007-02-08 メルク　エンド　カムパニー　インコーポレーテッド アルツハイマー病の治療のための大員環β−セクレターゼ阻害剤
WO2005018424A2 (en) 2003-08-18 2005-03-03 Research Foundation For Mental Hygiene, Inc. Antibodies specific for fibrillar amyloid and a procedure to detect fibrillar amyloid deposits
WO2005023762A1 (en) 2003-09-04 2005-03-17 Abbott Laboratories Pyrrolidine-2-carbonitrile derivatives and their use as inhibitors of dipeptidyl peptidase-iv (dpp-iv)
WO2005023858A1 (en) 2003-09-05 2005-03-17 Cellzome Ag Protein complexes associated with app-processing
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
US20050065144A1 (en) 2003-09-08 2005-03-24 Syrrx, Inc. Dipeptidyl peptidase inhibitors
CA2538220A1 (en) 2003-09-09 2005-03-24 Takeda Pharmaceutical Company Limited Use of antibody
WO2005025554A2 (en) 2003-09-09 2005-03-24 Japan Tobacco Inc. Dipeptidyl peptidase iv inhibitor
GB0322140D0 (en) 2003-09-22 2003-10-22 Pfizer Ltd Combinations
WO2005030731A1 (en) 2003-09-24 2005-04-07 Merck Sharp & Dohme Limited Gamma-secretase inhibitors
WO2005032471A2 (en) 2003-10-03 2005-04-14 Merck & Co., Inc. Benzylether and benzylamino beta-secretase inhibitors for the treatment of alzheimer's disease
SI1673347T1 (sl) 2003-10-06 2015-10-30 F. Hoffmann - La Roche Ag Substituirani derivati dibenzo-azepina in benzo-diazepina, ki so uporabni kot inhibitorji gama-sekretaze
CA2534634A1 (en) 2003-10-06 2005-04-14 Torrent Pharmaceuticals Ltd. Azolidinecarbonitriles and their use as dpp-iv inhibitors
US20070021414A1 (en) 2003-10-08 2007-01-25 Pfizer, Inc. 1-'2-(4-Hydroxyphenyl)-2-hydroxyethyl!-piperidin-4-ol compounds as nmda receptor antagonists
AU2004283461B2 (en) 2003-10-15 2010-02-11 Probiodrug Ag Use of effectors of glutaminyl and glutamate cyclases
GB0324236D0 (en) 2003-10-16 2003-11-19 Astrazeneca Ab Chemical compounds
WO2005039580A1 (en) 2003-10-16 2005-05-06 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an acetylcholinesterase inhibitor
TW200519105A (en) 2003-10-20 2005-06-16 Lg Life Science Ltd Novel inhibitors of DPP-IV, methods of preparing the same, and pharmaceutical compositions containing the same as an active agent
AU2004316119B2 (en) 2003-10-22 2008-04-24 Merz Pharma Gmbh & Co. Kgaa The use of 1-aminocyclohexane derivatives to modify deposition of fibrillogenic AB peptides in amyloidopathies
WO2006058720A2 (en) 2003-11-03 2006-06-08 Probiodrug Ag Novel compounds for the treatment of neurological disorders
CA2541212A1 (en) 2003-11-04 2005-05-19 Wallace T. Ashton Fused phenylalanine derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
WO2005044830A1 (en) 2003-11-11 2005-05-19 F. Hoffmann-La Roche Ag Phosphinic acids derivatives, beta-secretase inhibitors for the treatment of alzheimer’s disease
AU2004288831B2 (en) 2003-11-12 2010-08-26 Phenomix Corporation Heterocyclic boronic acid compounds
CA2546142A1 (en) 2003-11-24 2005-06-09 Merck & Co., Inc. Benzylether and benzylamino beta-secretase inhibitors for the treatment of alzheimer's disease
DE10355304A1 (de) 2003-11-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
UY28650A1 (es) 2003-12-05 2005-02-28 Forest Laboratories Memantina para la prevencion o disminucion de la conducta suicida y para el tratamiento de la depresion mayor asociada con esta conducta
EP1541143A1 (en) 2003-12-09 2005-06-15 Graffinity Pharmaceuticals Aktiengesellschaft Dpp-iv inhibitors
EP1541148A1 (en) 2003-12-09 2005-06-15 Graffinity Pharmaceuticals Aktiengesellschaft Dpp-iv inhibitors
WO2005058849A1 (en) 2003-12-15 2005-06-30 Glenmark Pharmaceuticals Ltd. New dipeptidyl peptidase in inhibitors; process for their preparation and compositions containing them
JP2007517781A (ja) 2003-12-19 2007-07-05 メルク　エンド　カムパニー　インコーポレーテッド アルツハイマー病治療用のフェニルアミドおよびピリジルアミド系β−セクレターゼ阻害薬
EP1708707A1 (en) 2004-01-22 2006-10-11 Neurosearch A/S Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an n-methyl-d-aspartate (nmda) receptors antagonist
EP1715843A1 (en) 2004-01-29 2006-11-02 Neuromolecular Inc. Combination of a nmda receptor antagonist and a mao-inhibitor or a gadph-inhibitor for the treatment of central nervous system-related conditions
WO2005075426A1 (en) 2004-02-03 2005-08-18 Glenmark Pharmaceuticals Ltd. Novel dipeptidyl peptidase iv inhibitors; processes for their preparation and compositions thereof
WO2005075436A2 (en) 2004-02-05 2005-08-18 Probiodrug Ag Novel inhibitors of glutaminyl cyclase
WO2005079756A2 (en) 2004-02-13 2005-09-01 Neuromolecular, Inc. Combination of a nmda receptor antagonist and an anti-depressive drug mao-inhibitor or a gadph-inhibitor for the treatment of psychiatric conditions
US20050182044A1 (en) 2004-02-17 2005-08-18 Bruinsma Gosse B. Combinatorial therapy with an acetylcholinesterase inhibitor and (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3,-b]indol-5-yl phenylcarbamate
AU2005219508B2 (en) 2004-02-18 2012-02-16 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthine, the production thereof and the use in the form of a DPP inhibitor
US7807157B2 (en) 2004-02-20 2010-10-05 Intellect Neurosciences Inc. Monoclonal antibodies and use thereof
AU2005216970B2 (en) 2004-02-23 2011-07-07 Trustees Of Tufts College Inhibitors of dipeptidylpeptidase IV for regulating glucose metabolism
EP1593671A1 (en) 2004-03-05 2005-11-09 Graffinity Pharmaceuticals AG DPP-IV inhibitors
KR100844593B1 (ko) 2004-03-09 2008-07-07 내셔날 헬스 리서치 인스티튜트 피롤리딘 화합물
CN102079743B (zh) 2004-03-15 2020-08-25 武田药品工业株式会社 二肽基肽酶抑制剂
JP2007529556A (ja) 2004-03-19 2007-10-25 アクソニクス インコーポレイテッド 認知障害の処置に有用なアセチルコリンエステラーゼ阻害剤およびｎ−メチル−ｄ−アスパラギン酸拮抗剤
JP4211648B2 (ja) 2004-03-22 2009-01-21 日本電気株式会社 ソフトウェアインストール方法およびシステム
WO2005095339A1 (en) 2004-03-31 2005-10-13 Pfizer Products Inc. Dicyanopyrrolidines as dipeptidyl peptidase iv inhibitors
WO2005097103A2 (en) 2004-04-01 2005-10-20 Axys Pharmaceuticals, Inc. Diabetes and metabolic syndrome therapy utilizing cathepsin b inhibitors
US20060004004A1 (en) 2004-04-05 2006-01-05 Schering Corporation Novel gamma secretase inhibitors
US7847100B2 (en) 2004-04-20 2010-12-07 Merck, Sharp & Dohme, Inc. 1,3,5-substituted phenyl derivative compounds useful as beta-secretase inhibitors for the treatment of Alzheimer's disease
AU2005236063A1 (en) 2004-04-20 2005-11-03 Merck & Co., Inc. 2, 4, 6-substituted pyridyl derivative compounds useful as beta-secretase inhibitors for the treatment of Alzheimer's disease
WO2005102390A2 (en) 2004-04-22 2005-11-03 Pfizer Japan, Inc. Combinations comprising alpha-2-delta ligands and nmda receptor antagonists
WO2005105133A2 (en) 2004-04-23 2005-11-10 Massachusetts Eye And Ear Infirmary Methods and compositions for preserving the viability of photoreceptor cells
CA2564432A1 (en) 2004-04-27 2005-11-10 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Human anti-amyloid .beta. peptide antibody and fragment of said antibody
WO2005108382A1 (en) 2004-05-04 2005-11-17 Merck & Co., Inc. 1,2,4-oxadiazole derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
EA011086B9 (ru) 2004-05-12 2012-08-30 Пфайзер Продактс Инк. Производные пролина и их применение в качестве ингибиторов дипептидилпептидазы iv
JP2007537257A (ja) 2004-05-13 2007-12-20 メルク　エンド　カムパニー　インコーポレーテッド アルツハイマー病の治療用ベータセクレターゼ阻害剤として有用なフェニルカルボキサミド化合物
WO2005116029A1 (en) 2004-05-18 2005-12-08 Merck & Co., Inc. Cyclohexylalanine derivatives as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
EP1598341A1 (en) 2004-05-21 2005-11-23 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft DPP-IV inhibitors
US7687638B2 (en) 2004-06-04 2010-03-30 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2005120571A2 (en) 2004-06-07 2005-12-22 Ramot At Tel Aviv University Ltd. Method of passive immunization against disease or disorder characterized by amyloid aggregation with diminished risk of neuroinflammation
EP1604980A1 (en) 2004-06-08 2005-12-14 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft DPP-IV inhibitors
EP1604662A1 (en) 2004-06-08 2005-12-14 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft 1-[(3R)-Amino-4-(2-fluoro-phenyl)-butyl]-pyrrolidine-(2R)-carboxylic acid benzyl amine derivatives and related compounds as dipeptidyl peptidase IV (DPP-IV) inhibitors for the treatment of type 2 diabetes mellitus
EP1604989A1 (en) 2004-06-08 2005-12-14 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft DPP-IV inhibitors
EP1758854B1 (en) 2004-06-15 2014-07-16 Merck Sharp & Dohme Corp. Pyrrolidin-3-yl compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease
GB0413389D0 (en) 2004-06-16 2004-07-21 Astrazeneca Ab Chemical compounds
SE0401601D0 (sv) 2004-06-21 2004-06-21 Bioarctic Neuroscience Ab Protofibril specific antibodies and uses thereof
US7482336B2 (en) 2004-06-21 2009-01-27 Merck & Co., Inc. Aminocyclohexanes as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
ATE461926T1 (de) 2004-06-30 2010-04-15 Schering Corp Substituierte n-arylsulfonylheterocyclische amine als gamma-sekretase-hemmer
US7371825B2 (en) 2004-06-30 2008-05-13 Centocor, Inc. Anti-MCP-1 antibodies, compositions, methods and uses
EP1769002A1 (en) 2004-07-02 2007-04-04 Northwestern University Monolocal antibodies that target pathological assemblies of amyloid beta; (abeta)
WO2006017292A1 (en) 2004-07-12 2006-02-16 Phenomix Corporation Constrained cyano compounds
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2006008661A2 (en) 2004-07-19 2006-01-26 Neurochem (International) Limited Diagnostic methods of multiple organ amyloidosis
US7955812B2 (en) 2004-07-19 2011-06-07 The General Hospital Corporation Methods of diagnosing alzheimer's disease by detecting antibodies to cross-linked β-amyloid oligomers
JP2008507538A (ja) 2004-07-22 2008-03-13 シェーリング　コーポレイション 置換アミドβセクレターゼインヒビター
CA2575340A1 (en) 2004-07-28 2006-02-09 Schering Corporation Macrocyclic beta-secretase inhibitors
HUP0401523A3 (en) 2004-07-29 2007-05-02 Richter Gedeon Vegyeszet Indole-2-carboxamide derivatives, pharmaceutical compositions containing them and process for producing them
AU2005290250A1 (en) 2004-07-30 2006-04-06 Rinat Neuroscience Corp. Antibodies directed against amyloid-beta peptide and methods using same
EP1623983A1 (en) 2004-08-05 2006-02-08 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft Heterocyclic compounds useful as DPP-IV inhibitors
CA2576405A1 (en) 2004-08-11 2006-02-16 Mitsubishi Chemical Corporation Antibody and utilization of the same
DE602005022320D1 (de) 2004-08-23 2010-08-26 Merck Sharp & Dohme Kondensierte triazolderivate als dipeptidylpeptidase-iv-hemmer zur behandlung bzw. prävention von diabetes
AU2005276631A1 (en) 2004-08-25 2006-03-02 Santhera Pharmaceuticals (Schweiz) Ag Alpha-keto carbonyl calpain inhibitors
AU2005276635A1 (en) 2004-08-25 2006-03-02 Santhera Pharmaceuticals (Schweiz) Ag Alpha-keto carbonyl calpain inhibitors
US7388007B2 (en) 2004-08-26 2008-06-17 Bristol-Myers Squibb Company Gamma-lactams as beta-secretase inhibitors
US7335491B2 (en) 2004-08-27 2008-02-26 Wyeth Research Ireland Limited Production of anti-abeta
EP1791818A1 (en) 2004-09-14 2007-06-06 The Genetics Company, Inc. Hydrazone derivatives and their use as beta secretase inhibitors
US7659289B2 (en) 2004-09-17 2010-02-09 Comentis, Inc. Hydroxyethylene-based β-secretase inhibitors and use thereof
JP2008513495A (ja) 2004-09-17 2008-05-01 コメンティス，インコーポレーテッド ベータ−セクレターゼ活性を阻害する二環式化合物およびその使用方法
WO2006058064A2 (en) 2004-11-29 2006-06-01 Merck & Co., Inc. Fused aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes
US20060246075A1 (en) 2004-09-29 2006-11-02 Marc Mercken Anti-amyloid antibodies, compositions, methods and uses
US7884104B2 (en) 2004-10-01 2011-02-08 Merck Sharp & Dohme Corp. Aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
WO2006042103A2 (en) 2004-10-05 2006-04-20 Axys Pharmaceuticals, Inc. Reversible inhibitors of cathepsin b
CA2580266A1 (en) 2004-10-08 2006-04-20 Novartis Ag Combination of organic compounds
EP1807087A2 (en) 2004-10-12 2007-07-18 Ernir Snorrason Inhibitors of acetylcholinesterase for treating skin diseases
WO2006044497A2 (en) 2004-10-13 2006-04-27 Merck & Co., Inc. Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzhermer’s disease
US20090004302A1 (en) 2004-10-15 2009-01-01 Biopharmacopae Design International Inc. Methods and Therapeutic Compositions Comprising Plant Extracts for the Treatment of Cancer
EP1807066A1 (en) 2004-10-25 2007-07-18 Novartis AG Combination of dpp-iv inhibitor, ppar antidiabetic and metformin
KR20070094890A (ko) 2004-10-25 2007-09-27 머크 앤드 캄파니 인코포레이티드 안티 ａｄｄｌ 항체 및 그 용도
BRPI0516674A (pt) 2004-10-28 2008-09-16 Sanko Junyaku Kk método de análise de mal de alzheimer e reagente de diagnóstico
EP1807396B1 (en) 2004-10-29 2013-06-26 Merck Sharp & Dohme Corp. 2-aminopyridine compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease
US7678783B2 (en) 2004-11-17 2010-03-16 Merck Sharp & Dohme Corp. Macrocyclic tertiary amine beta-secretase inhibitors for the treatment of alzheimer's disease
JP4235162B2 (ja) 2004-11-18 2009-03-11 日本電信電話株式会社 画像符号化装置，画像符号化方法，画像符号化プログラムおよびコンピュータ読み取り可能な記録媒体
US7951949B2 (en) 2004-11-23 2011-05-31 Merck, Sharp & Dohme, Corp. Macrocyclic aminopyridyl beta-secretase inhibitors for the treatment of Alzheimer's disease
AU2005309760A1 (en) 2004-11-23 2006-06-01 Merck & Co., Inc. 2,3,4,6-substituted pyridyl derivative compounds useful as beta-secretase inhibitors for the treatment of Alzheimer's disease
AU2005309601A1 (en) 2004-11-23 2006-06-01 Neuromolecular Pharmaceuticals, Inc. Composition comprising a sustained release coating or matrix and an NMDA receptor antagonist, method for administration such NMDA antagonist to a subject
EP2623099A1 (en) 2004-11-24 2013-08-07 Neuromolecular Pharmaceuticals, Inc Composition and method for treating neurological disease
CN101107247B (zh) 2004-11-30 2011-10-19 霍夫曼-拉罗奇有限公司 作为用于治疗糖尿病的dpp-iv抑制剂的取代的苯并喹嗪衍生物
EP1827478A4 (en) 2004-12-03 2009-08-05 Mucosal Therapeutics Llc METHODS OF TREATING JOINED OR SICK JOINTS
US20060257396A1 (en) 2004-12-15 2006-11-16 Jacobsen Jack S Abeta antibodies for use in improving cognition
ES2396555T3 (es) 2004-12-15 2013-02-22 Janssen Alzheimer Immunotherapy Anticuerpos que reconocen péptido beta amiloide
WO2006066233A1 (en) 2004-12-15 2006-06-22 Neuralab Limited An immunoprecipitation-based assay for predicting in vivo efficacy of beta-amyloid antibodies
EP1838348B1 (en) 2004-12-15 2013-06-26 Janssen Alzheimer Immunotherapy Humanized amyloid beta antibodies for use in improving cognition
BRPI0519585A2 (pt) 2004-12-20 2009-02-25 Hoffmann La Roche compostos de fàrmula i; processo para a fabricaÇço de compostos de fàrmula i; composiÇÕes farmacÊuticas; mÉtodo para o tratamento e/ou profilaxia de doenÇas que estço associadas com a dpp-iv e usos destes compostos
US7411093B2 (en) 2004-12-20 2008-08-12 Hoffman-La Roche Inc. Aminocycloalkanes as DPP-IV inhibitors
JP2008524331A (ja) 2004-12-21 2008-07-10 武田薬品工業株式会社 ジペプチジルペプチダーゼ阻害剤
EP2425846A1 (en) 2004-12-23 2012-03-07 Voyager Pharmaceutical Corporation Acetylcholinesterase Inhibitors and leuprolide acetate for the treatment of Alzheimer's disease
EP1831172B1 (en) 2004-12-28 2009-02-18 Council of Scientific and Industrial Research Substituted carbamic acid quinolin-6-yl esters useful as acetylcholinesterase inhibitors
CA2593545A1 (en) 2005-01-06 2006-07-13 Merck & Co., Inc. Drug combination therapy and pharmaceutical compositions for treating inflammatory disorders
US7820674B2 (en) 2005-01-19 2010-10-26 Merck, Sharp & Dohme Corp. Aminomethyl beta-secretase inhibitors for the treatment of alzheimer's disease
WO2006081171A1 (en) 2005-01-24 2006-08-03 Amgen Inc. Humanized anti-amyloid antibody
TW200640529A (en) 2005-02-28 2006-12-01 Thomas Christian Lines Composition for treating mental health disorders
EP1858501A1 (en) 2005-03-07 2007-11-28 Michael Hermanussen Nmda receptor antagonists in the medical intervention of metabolic disorders
ES2259270B1 (es) 2005-03-09 2007-11-01 Consejo Superior De Investigaciones Cientificas Metodo de diagnostico in vitro de la enfermedad de alzheimer mediante un anticuerpo monoclonal.
JP4883005B2 (ja) 2005-03-09 2012-02-22 コニカミノルタエムジー株式会社 希土類賦活アルカリ土類金属フッ化ハロゲン化物輝尽性蛍光体及びそれを用いた放射線画像変換パネル
WO2006099352A1 (en) 2005-03-10 2006-09-21 Bristol-Myers Squibb Company Novel isophthalates as beta-secretase inhibitors
FR2883285B1 (fr) 2005-03-17 2007-05-18 Sanofi Aventis Sa Sel besylate de la 7-(2-(4-(3-trifluoromethyl-phenyl) -1,2,3,6-tetrahudro-pyrid-1-yl)ethyl) isoquinoleine, sa preparation et son utilisation en therapeutique
ES2318918B1 (es) 2005-04-01 2010-02-16 Biotherapix Molecular Medicines, S.L.U. Anticuerpos humanos con capacidad de union al peptido beta-amiloide y sus aplicaciones.
BRPI0609915A2 (pt) 2005-04-27 2010-05-25 Novartis Ag métodos para tratar aterosclerose
PE20061323A1 (es) 2005-04-29 2007-02-09 Rinat Neuroscience Corp Anticuerpos dirigidos contra el peptido amiloide beta y metodos que utilizan los mismos
TW200716174A (en) 2005-05-19 2007-05-01 Centocor Inc Anti-MCP-1 antibodies, compositions, methods and uses
US7741448B2 (en) 2005-06-21 2010-06-22 Medical & Biological Laboratories Co., Ltd. Antibody having inhibitory effect on amyloid fibril formation
CA2633399C (en) 2005-12-12 2016-01-26 Ac Immune S.A. Therapeutic vaccine
NZ568012A (en) 2005-12-12 2012-07-27 Ac Immune Sa A beta 1-42 specific monoclonal antibodies with therapeutic properties
GB0704100D0 (en) 2006-03-17 2007-04-11 Vodafone Plc Improvements in an ehspa architecture
RU2498999C2 (ru) 2006-07-14 2013-11-20 Ац Иммуне Са Гуманизированное антитело к амилоиду бета
US8278345B2 (en) * 2006-11-09 2012-10-02 Probiodrug Ag Inhibitors of glutaminyl cyclase
JP5599614B2 (ja) 2006-11-09 2014-10-01 プロビオドルグ エージー グルタミニルシクラーゼの新規阻害剤
ES2468546T3 (es) * 2006-11-09 2014-06-16 Probiodrug Ag Nuevos inhibidores de glutaminil ciclasa
ATE554085T1 (de) 2006-11-30 2012-05-15 Probiodrug Ag Neue inhibitoren von glutaminylcyclase
MX2011002106A (es) * 2008-09-04 2011-04-07 Probiodrug Ag Inhibidores novedosos.
PL2475428T3 (pl) * 2009-09-11 2015-12-31 Probiodrug Ag Pochodne heterocykliczne jako inhibitory cyklazy glutaminowej
MX2012010470A (es) 2010-03-10 2012-10-09 Probiodrug Ag Inhibidores heterociclicos d ciclasa de glutaminilo (qc, ec .3 2. 5).

Also Published As

Publication number Publication date
US8530670B2 (en) 2013-09-10
EP2686313B1 (en) 2016-02-03
DK2686313T3 (en) 2016-05-02
US20120237475A1 (en) 2012-09-20
EP2686313A1 (en) 2014-01-22
JP2014508184A (ja) 2014-04-03
WO2012123563A1 (en) 2012-09-20
ES2570167T3 (es) 2016-05-17

Similar Documents

Publication Publication Date Title
JP5688745B2 (ja) グルタミニルシクラーゼ（ｑｃ、ｅｃ２．３．２．５）の複素環阻害剤
JP5612860B2 (ja) グルタミニルシクラーゼ阻害剤としてのイミダゾ［１，５−ａ］ピリジン誘導体
JP5675340B2 (ja) 新規阻害剤
JP5523107B2 (ja) グルタミニルシクラーゼの新規阻害剤
JP5934645B2 (ja) グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
JP5707327B2 (ja) 新規の阻害剤
JP5798157B2 (ja) 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
JP6026284B2 (ja) グルタミニルシクラーゼの阻害剤
JP5667440B2 (ja) グルタミニルシクラーゼ阻害剤としてのチオ尿素誘導体
JP5675343B2 (ja) グルタミニルシクラーゼ阻害剤としての尿素誘導体
JP5675342B2 (ja) グルタミニルシクラーゼ阻害剤としてのシアノグアニジン誘導体
JP6454651B2 (ja) 新規阻害剤
JP5675344B2 (ja) グルタミニルシクラーゼ阻害剤としてのニトロビニルジアミン誘導体
DK2686313T3 (en) Benzimidazole derivatives as inhibitors of glutaminyl cyclase
JP2010509285A (ja) グルタミニルシクラーゼの新規阻害剤
JP5945532B2 (ja) 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

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150313

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20150313

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20151112

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20151215

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20160311

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160615

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20160712

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20161011

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20161108

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20161124

R150 Certificate of patent or registration of utility model

Ref document number: 6050264

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

S533 Written request for registration of change of name

Free format text: JAPANESE INTERMEDIATE CODE: R313533

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250