RU2012103671A - Пептидные эпоксикетоны для ингибирования протеасомы - Google Patents

Пептидные эпоксикетоны для ингибирования протеасомы Download PDF

Info

Publication number
RU2012103671A
RU2012103671A RU2012103671/04A RU2012103671A RU2012103671A RU 2012103671 A RU2012103671 A RU 2012103671A RU 2012103671/04 A RU2012103671/04 A RU 2012103671/04A RU 2012103671 A RU2012103671 A RU 2012103671A RU 2012103671 A RU2012103671 A RU 2012103671A
Authority
RU
Russia
Prior art keywords
alkyl
compound according
zaz
6alkyl
hydrogen
Prior art date
Application number
RU2012103671/04A
Other languages
English (en)
Inventor
Кевин Д. Шенк
Франческо Парлати
Хань-Цзе ЧЖОУ
Катрин СИЛЬВЕН
Марк С. СМИТ
Марк К. Беннетт
Гай Дж. Лэйдиг
Original Assignee
Протеоликс, Инк.
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 Протеоликс, Инк. filed Critical Протеоликс, Инк.
Publication of RU2012103671A publication Critical patent/RU2012103671A/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • 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
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P25/28—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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06043—Leu-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06086—Dipeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06086—Dipeptides with the first amino acid being basic
    • C07K5/06095—Arg-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0819—Tripeptides with the first amino acid being acidic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Communicable Diseases (AREA)
  • Cardiology (AREA)
  • Virology (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)

Abstract

1. Соединение, имеющее структуру формулы (I), или его фармацевтически приемлемая соль,где каждый Ar независимо представляет собой ароматическую группу, необязательно замещенную 1-4 заместителями;каждый A независимо выбран из C=O, C=S и SO; илиА необязательно представляет собой ковалентную связь, когда является смежным по отношению к присутствующему Z;В отсутствует или представляет собой N(R)R;L отсутствует;М отсутствует или представляет собой Салкил;Q отсутствует;Х выбран из О, S, NH и N-Салкила;Y отсутствует или выбран из С=О и SO;каждый Z независимо выбран из О, S, NH и N-Салкила; илиZ необязательно представляет собой ковалентную связь, когда является смежным по отношению к присутствующему А;Rвыбран из Н, -Салкил-В, Сгидроксиалкила, Салкоксиалкила, арила и Сарилалкила;Rи R, каждый независимо, выбран из арила, Сарилалкила, гетероарила и Сгетероарилалкила;Rпредставляет собой N(R)L-Q-R;Rпредставляет собой H;Rвыбран из водорода, Салкила, Салкенила, Салкинила, Ar-Y-, карбоциклила, гетероциклила, N-концевой защитной группы, арила, Сарилалкила, RZAZ-Cалкила-, RZ-Cалкила-, (RO)(RO)P(=O)O-Cалкил-ZAZ-Салкила-, RZAZ-Cалкил-ZAZ-Cалкила-, гетероциклилМZAZ-Cалкила-, (RO)(RO)P(=O)O-Cалкила-, (R)N-Cалкила-, (R)N-Cалкила-, гетероциклилМ-, карбоциклилМ-, RSOCалкила- и RSONH, илиRи R, вместе представляют собой Салкил-Y-Салкил, Салкил-ZAZ-Салкил, ZAZ-Cалкил-ZAZ-Салкил, ZAZ-Салкил-ZAZ или Салкил-А, тем самым образуя кольцо;Rи Rнезависимо выбраны из водорода, Салкила и Сарилалкила;Rвыбран из водорода, ОН и Салкила; иRпредставляет собой N-концевую защитную группу;Rи Rнезависимо выбраны из водорода, катиона металла, Салкила, Салкенила, Салкинила, арила и Сарилалкила;каждый Rнезависимо выбран из водорода и Салкила; иRнезависим�

Claims (30)

1. Соединение, имеющее структуру формулы (I), или его фармацевтически приемлемая соль,
Figure 00000001
где каждый Ar независимо представляет собой ароматическую группу, необязательно замещенную 1-4 заместителями;
каждый A независимо выбран из C=O, C=S и SO2; или
А необязательно представляет собой ковалентную связь, когда является смежным по отношению к присутствующему Z;
В отсутствует или представляет собой N(R9)R10;
L отсутствует;
М отсутствует или представляет собой С1-12алкил;
Q отсутствует;
Х выбран из О, S, NH и N-С1-6алкила;
Y отсутствует или выбран из С=О и SO2;
каждый Z независимо выбран из О, S, NH и N-С1-6алкила; или
Z необязательно представляет собой ковалентную связь, когда является смежным по отношению к присутствующему А;
R1 выбран из Н, -С1-6алкил-В, С1-6гидроксиалкила, С1-6алкоксиалкила, арила и С1-6арилалкила;
R2 и R3, каждый независимо, выбран из арила, С1-6арилалкила, гетероарила и С1-6гетероарилалкила;
R4 представляет собой N(R5)L-Q-R6;
R5 представляет собой H;
R6 выбран из водорода, С1-6алкила, С2-6алкенила, С2-6алкинила, Ar-Y-, карбоциклила, гетероциклила, N-концевой защитной группы, арила, С1-6арилалкила, R11ZAZ-C1-8алкила-, R14Z-C1-8алкила-, (R11O)(R12O)P(=O)O-C1-8алкил-ZAZ-С1-8алкила-, R11ZAZ-C1-8алкил-ZAZ-C1-8алкила-, гетероциклилМZAZ-C1-8алкила-, (R11O)(R12O)P(=O)O-C1-8алкила-, (R13)2N-C1-12алкила-, (R13)3N+-C1-12алкила-, гетероциклилМ-, карбоциклилМ-, R14SO2C1-8алкила- и R14SO2NH, или
R5 и R6, вместе представляют собой С1-6алкил-Y-С1-6алкил, С1-6алкил-ZAZ-С1-6алкил, ZAZ-C1-6алкил-ZAZ-С1-6алкил, ZAZ-С1-6алкил-ZAZ или С1-6алкил-А, тем самым образуя кольцо;
R7 и R8 независимо выбраны из водорода, С1-6алкила и С1-6арилалкила;
R9 выбран из водорода, ОН и С1-6алкила; и
R10 представляет собой N-концевую защитную группу;
R11 и R12 независимо выбраны из водорода, катиона металла, С1-6алкила, С2-6алкенила, С2-6алкинила, арила и С1-6арилалкила;
каждый R13 независимо выбран из водорода и С1-6алкила; и
R14 независимо выбран из водорода, С1-6алкила, С2-6алкенила, С2-6алкинила, карбоциклила, гетероциклила, арила и С1-6арилалкила;
R15 выбран из водорода, С1-6алкила, С1-6гидроксиалкила, С1-6алкокси, -С(О)ОС1-6алкила, -С(О)NHC1-6алкила и С1-6арилалкила;
при условии, что в любом случае присутствия последовательности ZAZ, по меньшей мере один член последовательности должен быть другим, чем ковалентная связь.
2. Соединение по п.1, где R6 представляет собой N-концевую защитную группу.
3. Соединение по п.2, где R6 выбран из трет-бутоксикарбонила, бензилоксикарбонила, бензоила, флуорен-9-илметоксикарбонила, трифенилметила и трихлорэтоксикарбонила.
4. Соединение по п.1, где углерод, имеющий заместитель R1, имеет стереохимическую конфигурацию D.
5. Соединение по п.1, где А представляет собой С=О.
6. Соединение по п.1, где М представляет собой С1-8алкил.
7. Соединение по п.1, где В отсутствует.
8. Соединение по п.1, где Х представляет собой О.
9. Соединение по п.1, где Z представляет собой О.
10. Соединение по п.1, где R7 и R8 представляют собой Н.
11. Соединение по п.1, где R9 представляет собой C1-6алкил.
12. Соединение по п.1, где R11 и R12 независимо выбраны из водорода, катиона металла и C1-6алкила.
13. Соединение по п.1, где R1 выбран из C1-6алкил-B и C1-6аралкила.
14. Соединение по п.13, где R1 замещен одним или несколькими заместителями, выбранными из гидрокси, галогена, амида, аминогруппы, карбоновой кислоты или ее соли, сложного эфира, тиола или простого тиоэфира.
15. Соединение по п.13, где R1 выбран из метила, этила, изопропила, карбоксиметила и бензила.
16. Соединение по п.1, где R2 выбран из C1-6аралкила и C1-6гетероаралкила.
17. Соединение по п.16, где R2 выбран из C1-6алкилфенила, C1-6алкилиндолила, C1-6алкилтиенила, C1-6алкилтиазолила и C1-6алкилизотиазолила.
18. Соединение по п.17, где R2 замещен одним или несколькими заместителями, выбранными из гидрокси, галогена, амида, аминогруппы, карбоновой кислоты или ее соли, сложного эфира, тиола и простого тиоэфира.
19. Соединение по п.17, где R2 замещен одним или несколькими заместителями, выбранными из алкила, тригалогеналкила, алкокси, гидрокси и циано.
20. Соединение по п.17, где R2 выбран из C1-6алкилфенила и C1-6алкилиндолила.
21. Соединение по п.1, где R3 выбран из C1-6аралкила C1-6 гетероаралкила.
22. Соединение по п.21, где R3 амещен одним или несколькими заместителями, выбранными из гидрокси, галогена, амида, аминогруппы, карбоновой кослоты или ее соли, сложного эфира, тиола или простого тиоэфира.
23. Соединение по п.21, где R3 замещен одним или несколькими заместителями, выбранными из алкила, тригалогеналкила, алкокси, гидрокси и циано.
24. Соединение по п.21, где R3 выбран из C1-6алкилфенила и C1-6 алкилиндолила.
25. Соединение по п.1, где R6 выбран из C1-6алкила, C2-6алкенила, C2-6алкинила, C1-6аралкила и C1-6гетероаралкила.
26. Соединение по п.1, где R6 выбран из бутила, аллила, пропаргила, фенилметила, 2-пиридила, 3-пиридила и 4-пиридила.
27. Соединение по п.1, где R7 и R8 независимо выбраны из водорода и C1-6алкила.
28. Соединение по п.1, где углерод, имеющий заместитель R2, имеет стереохимическую конфигурацию D.
29. Соединение по п.1, где углерод, имеющий заместитель R3, имеет стереохимическую конфигурацию D.
30. Фармацевтическая композиция, содержащая соединение по п.1 или его фармацевтически приемлемую соль и фармацевтически приемлемый носитель.
RU2012103671/04A 2006-06-19 2012-02-02 Пептидные эпоксикетоны для ингибирования протеасомы RU2012103671A (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81521806P 2006-06-19 2006-06-19
US60/815,218 2006-06-19

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
RU2009101319/04A Division RU2450016C2 (ru) 2006-06-19 2007-06-19 Пептидные эпоксикетоны для ингибирования протеасомы

Publications (1)

Publication Number Publication Date
RU2012103671A true RU2012103671A (ru) 2013-08-10

Family

ID=38690245

Family Applications (2)

Application Number Title Priority Date Filing Date
RU2009101319/04A RU2450016C2 (ru) 2006-06-19 2007-06-19 Пептидные эпоксикетоны для ингибирования протеасомы
RU2012103671/04A RU2012103671A (ru) 2006-06-19 2012-02-02 Пептидные эпоксикетоны для ингибирования протеасомы

Family Applications Before (1)

Application Number Title Priority Date Filing Date
RU2009101319/04A RU2450016C2 (ru) 2006-06-19 2007-06-19 Пептидные эпоксикетоны для ингибирования протеасомы

Country Status (24)

Country Link
US (11) US7691852B2 (ru)
EP (2) EP2484688B1 (ru)
JP (2) JP5226679B2 (ru)
KR (1) KR101441703B1 (ru)
CN (1) CN101506224B (ru)
AU (1) AU2007261345B2 (ru)
BR (1) BRPI0713309A2 (ru)
CA (1) CA2657213C (ru)
CO (1) CO6241190A2 (ru)
CY (1) CY1114518T1 (ru)
DK (1) DK2041158T3 (ru)
ES (1) ES2415632T3 (ru)
IL (2) IL196064A (ru)
MX (1) MX2008016512A (ru)
MY (2) MY183014A (ru)
NZ (4) NZ597545A (ru)
PH (1) PH12012501747A1 (ru)
PL (1) PL2041158T3 (ru)
PT (1) PT2041158E (ru)
RU (2) RU2450016C2 (ru)
SI (1) SI2041158T1 (ru)
UA (1) UA101303C2 (ru)
WO (1) WO2007149512A2 (ru)
ZA (2) ZA200810765B (ru)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE494298T1 (de) 2004-04-15 2011-01-15 Proteolix Inc Verbindungen zur proteasomenzymhemmung
US8198270B2 (en) 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
SI2030981T1 (sl) 2004-05-10 2014-11-28 Onyx Therapeutics, Inc. Spojine za inhibiranje proteasomskega encima
EP2623113B1 (en) 2005-11-09 2017-05-31 Onyx Therapeutics, Inc. Compound for enzyme inhibition
NZ597545A (en) 2006-06-19 2013-07-26 Proteolix Inc Peptide epoxyketones for proteasome inhibition
CA2701778C (en) 2007-10-04 2018-09-11 Onyx Therapeutics, Inc. Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
JP5675629B2 (ja) * 2008-10-21 2015-02-25 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． ペプチドエポキシケトンを用いた併用療法
AR075899A1 (es) 2009-03-20 2011-05-04 Onyx Therapeutics Inc Tripeptidos epoxicetonas cristalinos inhibidores de proteasa
WO2011060179A1 (en) * 2009-11-13 2011-05-19 Onyx Therapeutics, Inc Use of peptide epoxyketones for metastasis suppression
AU2011223795B2 (en) 2010-03-01 2015-11-05 Onyx Therapeutics, Inc. Compounds for immunoproteasome inhibition
CA2795559A1 (en) * 2010-04-07 2011-11-03 Onyx Therapeutics, Inc. Crystalline peptide epoxyketone immunoproteasome inhibitor
US8609610B2 (en) * 2011-02-18 2013-12-17 Trustees Of Dartmouth College Inhibitors of the trypsin-like site of the proteasome and methods of use thereof
AU2012222812A1 (en) * 2011-02-28 2013-05-02 Mcmaster University Treatment of cancer with dopamine receptor antagonists
WO2013009923A1 (en) * 2011-07-13 2013-01-17 Creighton University Methods of promoting neuron growth
JP6176259B2 (ja) 2012-06-29 2017-08-09 日産化学工業株式会社 立体選択的なエポキシケトン化合物の製造方法
WO2014011695A2 (en) 2012-07-09 2014-01-16 Onyx Therapeutics, Inc. Prodrugs of peptide epoxy ketone protease inhibitors
CA2881999A1 (en) * 2012-08-14 2014-02-20 Abdelmalik Slassi Fluorinated epoxyketone-based compounds and uses thereof as proteasome inhibitors
KR20150068464A (ko) * 2012-10-12 2015-06-19 에프. 호프만-라 로슈 아게 매크로사이클릭 케토아미드 면역프로테아좀 억제제
AR095426A1 (es) * 2013-03-14 2015-10-14 Onyx Therapeutics Inc Inhibidores tripeptídicos de la epoxicetona proteasa
SG11201507106PA (en) * 2013-03-14 2015-10-29 Onyx Therapeutics Inc Dipeptide and tripeptide epoxy ketone protease inhibitors
CN104174021A (zh) * 2013-05-22 2014-12-03 复旦大学附属华山医院 蛋白酶体抑制剂在制备治疗慢性低度炎症性疾病药物中的用途
WO2015032621A1 (en) * 2013-09-06 2015-03-12 Sandoz Ag Synthesis of peptide epoxy ketones
ES2748434T3 (es) 2014-01-10 2020-03-16 Univ Cornell Dipéptidos como inhibidores de inmunoproteasomas humanos
JP6551825B2 (ja) * 2014-02-10 2019-07-31 公立大学法人首都大学東京 クロマチン構造制御剤
DE102014010220A1 (de) 2014-07-10 2016-01-14 Immunologik Gmbh Mittel zur Behandlung retroviraler Infektionen
WO2016022955A1 (en) 2014-08-07 2016-02-11 Mayo Foundation For Medical Education And Research Compounds and methods for treating cancer
US11202817B2 (en) 2014-08-18 2021-12-21 Cornell University Dipeptidomimetics as inhibitors of human immunoproteasomes
CN105017181B (zh) * 2015-07-02 2017-10-10 南京师范大学 卡非佐米关键中间体及其衍生物的制备方法
WO2017032487A1 (en) 2015-08-27 2017-03-02 Technische Universität München Proteasome inhibitor comprising a signal-emitting moiety
EP4006012A1 (en) 2015-10-15 2022-06-01 Cornell University Proteasome inhibitors and uses thereof
WO2018005781A1 (en) 2016-06-29 2018-01-04 Kezar Life Sciences Process of preparing a peptide epoxyketone immunoproteasome inhibitor, and precursors thereof
CA3029032C (en) 2016-06-29 2024-10-29 Kezar Life Sciences CRYSTAL SALTS OF AN IMMUNOPROTEASOME PEPTIDE INHIBITOR EPOXYCETONE
EP3330260A1 (en) 2016-12-01 2018-06-06 Enantia, S.L. Process for the preparation of an intermediate for the synthesis of i.a. carfilzomib
WO2018160717A1 (en) 2017-02-28 2018-09-07 Mayo Foundation For Medical Education And Research Compounds and methods for treating cancer
WO2018213263A1 (en) * 2017-05-15 2018-11-22 The Regents Of The University Of California Immunoproteasome inhibitor
CN111601597B (zh) 2017-08-23 2023-10-13 科智生命科学公司 自身免疫性病症的治疗中的免疫蛋白酶体抑制剂和免疫抑制剂
WO2019075252A1 (en) 2017-10-11 2019-04-18 Cornell University PEPTIDOMIMETIC INHIBITORS OF PROTEASOME
US11243207B2 (en) 2018-03-29 2022-02-08 Mayo Foundation For Medical Education And Research Assessing and treating cancer
JP7344486B2 (ja) 2018-03-30 2023-09-14 国立大学法人京都大学 心筋細胞成熟促進剤
WO2021108705A2 (en) * 2019-11-25 2021-06-03 Cornell University Nuclear factor kappa b pathway inhibition to arrest calcific aortic stenosis
JP2023545031A (ja) * 2020-10-05 2023-10-26 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング 血液疾患および固形腫瘍の処置のためのｌｍｐ７選択的阻害剤

Family Cites Families (90)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4733665C2 (en) 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US5135919A (en) 1988-01-19 1992-08-04 Children's Medical Center Corporation Method and a pharmaceutical composition for the inhibition of angiogenesis
US5441944A (en) 1989-04-23 1995-08-15 The Trustees Of The University Of Pennsylvania Substituted cyclodextrin sulfates and their uses as growth modulating agents
US5071957A (en) 1989-08-04 1991-12-10 Bristol-Myers Company Antibiotic BU-4061T
US4990448A (en) 1989-08-04 1991-02-05 Bristol-Myers Company Bu-4061T
US5376645A (en) 1990-01-23 1994-12-27 University Of Kansas Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
KR0166088B1 (ko) 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
HUT62312A (en) 1990-03-05 1993-04-28 Cephalon Inc Process for producing chymotrypsin-like proteases and their inhibitors
US5340736A (en) 1991-05-13 1994-08-23 The President & Fellows Of Harvard College ATP-dependent protease and use of inhibitors for same in the treatment of cachexia and muscle wasting
GB9300048D0 (en) * 1993-01-04 1993-03-03 Wellcome Found Endothelin converting enzyme inhibitors
TW380137B (en) 1994-03-04 2000-01-21 Merck & Co Inc Process for making an epoxide
US5693617A (en) 1994-03-15 1997-12-02 Proscript, Inc. Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein
US6660268B1 (en) 1994-03-18 2003-12-09 The President And Fellows Of Harvard College Proteasome regulation of NF-KB activity
US6506876B1 (en) 1994-10-11 2003-01-14 G.D. Searle & Co. LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use
US6083903A (en) 1994-10-28 2000-07-04 Leukosite, Inc. Boronic ester and acid compounds, synthesis and uses
DE19505263A1 (de) 1995-02-16 1996-08-22 Consortium Elektrochem Ind Verfahren zur Reinigung von wasserlöslichen Cyclodextrinderivaten
US6335358B1 (en) 1995-04-12 2002-01-01 President And Fellows Of Harvard College Lactacystin analogs
US6150415A (en) 1996-08-13 2000-11-21 The Regents Of The University Of California Epoxide hydrolase complexes and methods therewith
WO1998010779A1 (en) 1996-09-13 1998-03-19 New York University Method for treating parasitic diseases with proteasome inhibitors
NZ335276A (en) 1996-10-18 2000-09-29 Vertex Pharma Inhibitors of serine proteases, particularly hepatitis C virus (HCV) NS3 (Non Structural Protein 3) protease
EP1136498A1 (en) 1996-10-18 2001-09-26 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hepatitis c virus NS3 protease
US5874418A (en) 1997-05-05 1999-02-23 Cydex, Inc. Sulfoalkyl ether cyclodextrin based solid pharmaceutical formulations and their use
US6046177A (en) 1997-05-05 2000-04-04 Cydex, Inc. Sulfoalkyl ether cyclodextrin based controlled release solid pharmaceutical formulations
ES2210769T3 (es) 1997-06-13 2004-07-01 Cydex Inc. Compuesto con vida de almacenamiento prolongada que comprende ciclodextrina y medicamentos y promedicamentos que se descomponen en componentes insolubles en agua.
US6133308A (en) 1997-08-15 2000-10-17 Millennium Pharmaceuticals, Inc. Synthesis of clasto-lactacystin beta-lactone and analogs thereof
US6075150A (en) 1998-01-26 2000-06-13 Cv Therapeutics, Inc. α-ketoamide inhibitors of 20S proteasome
US6099851A (en) 1998-06-02 2000-08-08 Weisman; Kenneth M. Therapeutic uses of leuprolide acetate
US6902721B1 (en) 1998-07-10 2005-06-07 Osteoscreen, Inc. Inhibitors of proteasomal activity for stimulating bone growth
US6462019B1 (en) 1998-07-10 2002-10-08 Osteoscreen, Inc. Inhibitors of proteasomal activity and production for stimulating bone growth
US6838436B1 (en) 1998-07-10 2005-01-04 Osteoscreen Inc. Inhibitors of proteasomal activity for stimulating bone growth
US6204257B1 (en) 1998-08-07 2001-03-20 Universtiy Of Kansas Water soluble prodrugs of hindered alcohols
AU762373B2 (en) 1998-10-20 2003-06-26 Millennium Pharmaceuticals, Inc. Method for monitoring proteasome inhibitor drug action
US6492333B1 (en) 1999-04-09 2002-12-10 Osteoscreen, Inc. Treatment of myeloma bone disease with proteasomal and NF-κB activity inhibitors
US6831099B1 (en) 1999-05-12 2004-12-14 Yale University Enzyme inhibition
JP2003528039A (ja) 1999-10-20 2003-09-24 オステオスクリーン，インコーポレイテッド 骨および毛成長を刺激するためのプロテアソーム活性のインヒビター
ES2272558T3 (es) 2000-10-12 2007-05-01 Viromics Gmbh Inhibidores del proteasoma para el tratamiento de infecciones causadas por virus de la hepatitis.
CA2435146C (en) 2001-01-25 2011-03-29 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Formulation of boronic acid compounds
ES2278049T3 (es) 2001-05-21 2007-08-01 Alcon, Inc. Uso de inhibidores de proteasoma para tratar trastornos de ojo seco.
WO2003033506A1 (en) 2001-10-12 2003-04-24 Kyorin Pharmaceutical Co., Ltd. Aminoborane acid derivative and proteasome inhibitory drug containing the same
EP1463719A2 (en) 2002-01-08 2004-10-06 Eisai Co., Ltd Eponemycin and epoxomicin analogs and uses thereof
US20040116329A1 (en) 2002-01-29 2004-06-17 Epstein Stephen E. Inhibition of proteasomes to prevent restenosis
AU2003220685A1 (en) 2002-04-09 2003-10-27 Greenville Hospital System Metastasis modulating activity of highly sulfated oligosaccharides
US7968569B2 (en) 2002-05-17 2011-06-28 Celgene Corporation Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
WO2003101481A1 (en) 2002-06-03 2003-12-11 Als Therapy Development Foundation Treatment of neurodegenerative diseases using proteasome modulators
US20030224469A1 (en) 2002-06-03 2003-12-04 Buchholz Tonia J. Methods and kits for assays utilizing fluorescence polarization
US20040167139A1 (en) 2002-07-26 2004-08-26 Potter David A. Methods of treating cancer
US7189740B2 (en) 2002-10-15 2007-03-13 Celgene Corporation Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes
MXPA05005923A (es) 2002-12-06 2005-09-21 Millennium Pharm Inc Metodos para la identificacion, valoracion y tratamiento de pacientes con terapia para la inhibicion de la proteasoma.
TW200418791A (en) 2003-01-23 2004-10-01 Bristol Myers Squibb Co Pharmaceutical compositions for inhibiting proteasome
CA2707750A1 (en) 2003-04-08 2004-10-21 Novartis Ag Solid pharmaceutical compositions comprising a s1p receptor agonist and a sugar alcohol
JP4653103B2 (ja) 2003-06-10 2011-03-16 ザ ジェイ．ディヴィッド グラッドストン インスティテューツ レンチウイルス感染症を治療するための方法
US7012063B2 (en) 2003-06-13 2006-03-14 Children's Medical Center Corporation Reducing axon degeneration with proteasome inhibitors
WO2005065435A2 (en) 2003-12-31 2005-07-21 Cydex, Inc. Et Al. Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
GB0400804D0 (en) 2004-01-14 2004-02-18 Innoscience Technology Bv Pharmaceutical compositions
ATE494298T1 (de) 2004-04-15 2011-01-15 Proteolix Inc Verbindungen zur proteasomenzymhemmung
US8198270B2 (en) 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
US7232818B2 (en) 2004-04-15 2007-06-19 Proteolix, Inc. Compounds for enzyme inhibition
SI2030981T1 (sl) 2004-05-10 2014-11-28 Onyx Therapeutics, Inc. Spojine za inhibiranje proteasomskega encima
AU2005243140A1 (en) 2004-05-10 2005-11-24 Proteolix, Inc. Synthesis of amino acid keto-epoxides
EP2100899A3 (en) 2004-10-20 2009-09-30 Proteolix, Inc. Compounds for proteasome enzyme inhibition
EP2261236B1 (en) 2004-12-07 2015-07-15 Onyx Therapeutics, Inc. Composition for proteasome inhibition
US7468383B2 (en) 2005-02-11 2008-12-23 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7589066B2 (en) * 2005-03-11 2009-09-15 The University Of North Carolina At Chapel Hill Potent and specific immunoproteasome inhibitors
EP1876893B1 (en) 2005-04-15 2012-04-11 Geron Corporation Cancer treatment by combined inhibition of proteasome and telomerase activities
GT200600350A (es) 2005-08-09 2007-03-28 Formulaciones líquidas
EP2623113B1 (en) 2005-11-09 2017-05-31 Onyx Therapeutics, Inc. Compound for enzyme inhibition
AR057227A1 (es) 2005-12-09 2007-11-21 Centocor Inc Metodo para usar antagonistas de il6 con inhibidores del proteasoma
US20070207950A1 (en) 2005-12-21 2007-09-06 Duke University Methods and compositions for regulating HDAC6 activity
WO2007122686A1 (ja) 2006-04-14 2007-11-01 Eisai R & D Management Co., Ltd. ベンズイミダゾール化合物
DE102006026464A1 (de) 2006-06-01 2007-12-06 Virologik Gmbh Innovationszentrum Medizintechnik Und Pharma Pharmazeutische Zusammensetzung zur Behandlung von Virusinfektionen und / oder Tumorerkrankungen durch Inhibition der Proteinfaltung und des Proteinabbaus
NZ597545A (en) 2006-06-19 2013-07-26 Proteolix Inc Peptide epoxyketones for proteasome inhibition
WO2008033807A2 (en) 2006-09-13 2008-03-20 The Arizona Board Of Regents On Behalf Of The University Of Arizona Synergistic combinations of antineoplastic thiol-binding mitochondrial oxidants and antineoplastic proteasome inhibitors for the treatment of cancer
MX2009007777A (es) 2007-01-23 2009-12-16 Gloucester Pharmaceuticals Inc Terapia de combinacion que comprende romidepsina y bortezomib.
JP4325683B2 (ja) 2007-02-14 2009-09-02 セイコーエプソン株式会社 画像表示装置、及び画像表示装置の制御方法
WO2008140782A2 (en) 2007-05-10 2008-11-20 Proteolix, Inc. Compounds for enzyme inhibition
KR20140042933A (ko) 2007-08-06 2014-04-07 밀레니엄 파머슈티컬스 인코퍼레이티드 프로테아좀 억제제
US7442830B1 (en) 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
CA2701778C (en) 2007-10-04 2018-09-11 Onyx Therapeutics, Inc. Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
US7838673B2 (en) 2007-10-16 2010-11-23 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
EP2212334B1 (en) 2007-10-16 2012-08-15 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
WO2009067453A1 (en) 2007-11-19 2009-05-28 Syndax Pharmaceuticals, Inc. Combinations of hdac inhibitors and proteasome inhibitors
SI2318419T2 (sl) 2008-06-17 2025-10-30 Takeda Pharmaceutical Company Limited Spojine boronat estra in njihovi farmacevtski sestavki
AR075090A1 (es) 2008-09-29 2011-03-09 Millennium Pharm Inc Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden.
JP5675629B2 (ja) 2008-10-21 2015-02-25 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． ペプチドエポキシケトンを用いた併用療法
AR075899A1 (es) 2009-03-20 2011-05-04 Onyx Therapeutics Inc Tripeptidos epoxicetonas cristalinos inhibidores de proteasa
CN101928329B (zh) 2009-06-19 2013-07-17 北京大学 三肽硼酸(酯)类化合物、其制备方法和应用
WO2011060179A1 (en) 2009-11-13 2011-05-19 Onyx Therapeutics, Inc Use of peptide epoxyketones for metastasis suppression
AU2011223795B2 (en) 2010-03-01 2015-11-05 Onyx Therapeutics, Inc. Compounds for immunoproteasome inhibition
AU2011235227B2 (en) 2010-03-31 2016-09-08 Millennium Pharmaceuticals, Inc. Derivatives of 1-amino-2-cyclopropylethylboronic acid
CA2795559A1 (en) 2010-04-07 2011-11-03 Onyx Therapeutics, Inc. Crystalline peptide epoxyketone immunoproteasome inhibitor

Also Published As

Publication number Publication date
ES2415632T3 (es) 2013-07-26
KR101441703B1 (ko) 2014-09-17
US20130053303A1 (en) 2013-02-28
UA101303C2 (ru) 2013-03-25
JP5226679B2 (ja) 2013-07-03
CY1114518T1 (el) 2016-10-05
US8080576B2 (en) 2011-12-20
EP2041158B1 (en) 2013-04-17
US8765745B2 (en) 2014-07-01
WO2007149512A2 (en) 2007-12-27
US20100144649A1 (en) 2010-06-10
US20140100169A1 (en) 2014-04-10
CN101506224B (zh) 2016-03-30
US20070293465A1 (en) 2007-12-20
US8080545B2 (en) 2011-12-20
IL196064A0 (en) 2009-09-01
NZ603303A (en) 2014-05-30
BRPI0713309A2 (pt) 2012-04-17
US20130041008A1 (en) 2013-02-14
US8357683B2 (en) 2013-01-22
CN101506224A (zh) 2009-08-12
NZ613252A (en) 2015-01-30
US20120088762A1 (en) 2012-04-12
US8431571B2 (en) 2013-04-30
NZ597545A (en) 2013-07-26
US7691852B2 (en) 2010-04-06
PT2041158E (pt) 2013-07-17
PH12012501747A1 (en) 2015-10-12
MX2008016512A (es) 2009-02-26
US9657058B2 (en) 2017-05-23
US20130035297A1 (en) 2013-02-07
US20150353601A1 (en) 2015-12-10
SI2041158T1 (sl) 2013-09-30
NZ573759A (en) 2012-03-30
IL218033A (en) 2015-07-30
RU2009101319A (ru) 2010-07-27
JP5740383B2 (ja) 2015-06-24
CA2657213C (en) 2017-01-03
US20140080753A1 (en) 2014-03-20
ZA201001834B (en) 2011-11-30
US20130338057A1 (en) 2013-12-19
RU2450016C2 (ru) 2012-05-10
MY147832A (en) 2013-01-31
ZA200810765B (en) 2010-05-26
PL2041158T3 (pl) 2013-08-30
CO6241190A2 (es) 2011-01-20
US8735441B2 (en) 2014-05-27
IL218033A0 (en) 2012-03-29
EP2041158A2 (en) 2009-04-01
DK2041158T3 (da) 2013-06-24
HK1128702A1 (en) 2009-11-06
US20100144648A1 (en) 2010-06-10
JP2013067623A (ja) 2013-04-18
EP2484688A1 (en) 2012-08-08
AU2007261345B2 (en) 2012-02-23
CA2657213A1 (en) 2007-12-27
IL196064A (en) 2015-10-29
JP2009541327A (ja) 2009-11-26
KR20090023477A (ko) 2009-03-04
US8609654B1 (en) 2013-12-17
AU2007261345A1 (en) 2007-12-27
MY183014A (en) 2021-02-05
EP2484688B1 (en) 2016-06-08
WO2007149512A3 (en) 2008-02-21

Similar Documents

Publication Publication Date Title
RU2009101319A (ru) Пептидные эпоксикетоны для ингибирования протеасомы
EP4483882A3 (en) New methylquinazolinone derivatives
TW200642683A (en) Heterocyclic compound
EP4491622A3 (en) Cardiac sarcomere inhibitors
EP4385996A3 (en) Novel spirobicyclic analogues
JP2009541327A5 (ru)
TW200738682A (en) Isoquinoline derivatives
MX2009003739A (es) Derivados de hidrobenzamida como inhibidores de hsp90.
RU2006143664A (ru) Соединения для ингибирования ферментов
JP2013521295A5 (ru)
MXPA04005880A (es) Cis-imidazolinas como inhibidores de la mdm2.
RU2013114189A (ru) Пролекарственная форма замещенного полициклического производного карбамоилпиридона
MY148636A (en) Benzimidazole derivatives
MY150289A (en) Derivatives of indole-2-carboxamides and of azaindole-2-carboxamides substituted with a silanyl group, preparation thereof and therapeutic use thereof
RU2009106934A (ru) Производное аминофосфата и модулятор рецептора s1p, содержащий его в качестве активного ингредиента
TW200736258A (en) Pyrimidine derivatives for the treatment of abnormal cell growth
RU2014148530A (ru) Производные дипептида лизин-глутаминовая кислота
WO2011147881A3 (de) Cyclische dipeptide als futtermitteladditive
JO2413B1 (en) Benzoxazine derivatives and their use
EP4316504A3 (en) Compounds
CR20210181A (es) Inhibidores de o-glicoproteína-2-acetamido-2-desoxi-3-d-glucopiranosidasa
PH12020552186A1 (en) Cyanotriazole compounds and uses thereof
MX2009003283A (es) Nuevos derivados imidazolonas, su preparacion como medicamentos, composiciones farmaceuticas y uso como inhibidores de proteinas quinasas, principalmente cdc7.
MXPA05013465A (es) Cis-imidazolinas como inhibidores de mdm2.
WO2006088720A3 (en) 9-substituted tetracyclines

Legal Events

Date Code Title Description
HZ9A Changing address for correspondence with an applicant
FA92 Acknowledgement of application withdrawn (lack of supplementary materials submitted)

Effective date: 20160512