EA030957B1 - Дипептидные и трипептидные эпоксикетонные ингибиторы протеазы - Google Patents

Дипептидные и трипептидные эпоксикетонные ингибиторы протеазы

Info

Publication number
EA030957B1
EA030957B1 EA201591752A EA201591752A EA030957B1 EA 030957 B1 EA030957 B1 EA 030957B1 EA 201591752 A EA201591752 A EA 201591752A EA 201591752 A EA201591752 A EA 201591752A EA 030957 B1 EA030957 B1 EA 030957B1
Authority
EA
Eurasian Patent Office
Prior art keywords
dipeptide
protease inhibitors
epoxy ketone
ketone protease
compounds
Prior art date
Application number
EA201591752A
Other languages
English (en)
Other versions
EA201591752A1 (ru
Inventor
Дастин Макминн
Генри Джонсон
Дэвид К. Мебиус
Original Assignee
Оникс Терапьютикс, 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 Оникс Терапьютикс, Инк. filed Critical Оникс Терапьютикс, Инк.
Publication of EA201591752A1 publication Critical patent/EA201591752A1/ru
Publication of EA030957B1 publication Critical patent/EA030957B1/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
    • C07K5/08—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • 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
    • 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
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P17/08—Antiseborrheics
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • A61P31/06—Antibacterial agents for tuberculosis
    • 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
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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
    • 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
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
    • 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
    • C07K5/0606—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
    • C07K5/06017—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
    • C07K5/06069—Ser-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
    • C07K5/06078—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
    • C07K5/06104—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
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C07K5/06121—Asp- or Asn-amino acid the second amino acid being 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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • 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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
    • 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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06173—Dipeptides with the first amino acid being heterocyclic and Glp-amino acid; Derivatives thereof
    • 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
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical 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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Pulmonology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)

Abstract

Предложены дипептидные и трипептидные эпоксикетонные ингибиторы протеазы, способы их получения, фармацевтические композиции на их основе и способы их применения. В частности, предложены соединения формулы (II)их фармацевтически приемлемые соли и содержащие их композиции. Также предложены конкретные соединения. Соединения и композиции, предложенные в данном описании, могут применяться, например, при лечении пролиферативных заболеваний, включая рак и аутоиммунные заболевания.
EA201591752A 2013-03-14 2014-03-14 Дипептидные и трипептидные эпоксикетонные ингибиторы протеазы EA030957B1 (ru)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201361786086P 2013-03-14 2013-03-14
US201361785608P 2013-03-14 2013-03-14
US201361847780P 2013-07-18 2013-07-18
US201361856847P 2013-07-22 2013-07-22
US201361883843P 2013-09-27 2013-09-27
US201361883798P 2013-09-27 2013-09-27
US201461941798P 2014-02-19 2014-02-19
PCT/US2014/026980 WO2014152127A1 (en) 2013-03-14 2014-03-14 Dipeptide and tripeptide epoxy ketone protease inhibitors

Publications (2)

Publication Number Publication Date
EA201591752A1 EA201591752A1 (ru) 2016-02-29
EA030957B1 true EA030957B1 (ru) 2018-10-31

Family

ID=50680148

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201591752A EA030957B1 (ru) 2013-03-14 2014-03-14 Дипептидные и трипептидные эпоксикетонные ингибиторы протеазы

Country Status (18)

Country Link
US (1) US9657057B2 (ru)
EP (1) EP2970225B1 (ru)
JP (2) JP2016515127A (ru)
KR (1) KR20150131276A (ru)
CN (1) CN105164117B (ru)
AU (2) AU2014240122B2 (ru)
BR (1) BR112015022856A8 (ru)
CA (1) CA2904085C (ru)
DK (1) DK2970225T3 (ru)
EA (1) EA030957B1 (ru)
ES (1) ES2687368T3 (ru)
IL (2) IL241180A0 (ru)
JO (1) JO3326B1 (ru)
MX (1) MX362489B (ru)
SG (1) SG11201507106PA (ru)
TW (1) TWI662047B (ru)
UY (1) UY35455A (ru)
WO (1) WO2014152127A1 (ru)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018005781A1 (en) 2016-06-29 2018-01-04 Kezar Life Sciences Process of preparing a peptide epoxyketone immunoproteasome inhibitor, and precursors thereof
KR102655020B1 (ko) 2016-06-29 2024-04-04 케자르 라이프 사이언스 펩티드 에폭시케톤 면역프로테아좀 억제제의 결정질 염
EP3318276A1 (en) * 2016-11-04 2018-05-09 Janssen Biotech, Inc. Combinations of a telomerase inhibitor and a bcl-2 inhibitor for the treatment of hematological cancers
WO2018213263A1 (en) * 2017-05-15 2018-11-22 The Regents Of The University Of California Immunoproteasome inhibitor
CN107652219B (zh) 2017-08-14 2021-06-08 上海新理念生物医药科技有限公司 四马来酰亚胺型连接子及其应用
CN117338932A (zh) * 2017-08-23 2024-01-05 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
WO2019060651A1 (en) 2017-09-21 2019-03-28 Kezar Life Sciences POLY THERAPY FOR IMMUNOLOGICAL DISEASES
CA3082786A1 (en) * 2017-11-16 2019-05-23 Amgen Inc. Stable compositions of pegylated carfilzomib compounds
WO2019133988A1 (en) 2017-12-30 2019-07-04 Unity Biotechnology, Inc. Peptide-based proteasome inhibitors for treating conditions mediated by senescent cells and for treating cancer
US10689416B2 (en) 2017-12-30 2020-06-23 Unity Biotechnology, Inc. Peptide-based proteasome inhibitors for treating conditions mediated by senescent cells and for treating cancer
CN110092813B (zh) * 2019-06-05 2021-05-11 南京师范大学 一种三肽环氧丙烷衍生物及其制备方法和用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070105786A1 (en) * 2005-11-09 2007-05-10 Proteolix, Inc. Compounds for enzyme inhibition
WO2007149512A2 (en) * 2006-06-19 2007-12-27 Proteolix, Inc. Peptide epoxyketones for pr0teas0me inhibition

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
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
US5858784A (en) 1991-12-17 1999-01-12 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol- and liposome-based delivery
WO1998010779A1 (en) 1996-09-13 1998-03-19 New York University Method for treating parasitic diseases with proteasome inhibitors
US6042820A (en) 1996-12-20 2000-03-28 Connaught Laboratories Limited Biodegradable copolymer containing α-hydroxy acid and α-amino acid units
US6472375B1 (en) 1998-04-16 2002-10-29 John Wayne Cancer Institute DNA vaccine and methods for its use
CN102372764A (zh) 2000-07-21 2012-03-14 先灵公司 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽
US7232818B2 (en) 2004-04-15 2007-06-19 Proteolix, Inc. Compounds for enzyme inhibition
ES2510840T3 (es) * 2004-05-10 2014-10-21 Onyx Therapeutics, Inc. Compuestos para la inhibición enzimática del proteosoma
ATE499109T1 (de) 2004-12-07 2011-03-15 Proteolix Inc Zusammensetzung zur proteasomhemmung
US7589066B2 (en) * 2005-03-11 2009-09-15 The University Of North Carolina At Chapel Hill Potent and specific immunoproteasome inhibitors
EP3090737A1 (en) 2008-10-21 2016-11-09 Onyx Therapeutics, Inc. Combination therapy with peptide epoxyketones
JP6042724B2 (ja) * 2010-03-01 2016-12-14 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． イムノプロテアソーム阻害のための化合物
US8455431B2 (en) * 2011-02-18 2013-06-04 Trustees of Dartmout College Inhibitors of the trypsin-like site of the proteasome and methods of use thereof
AU2012238318B2 (en) 2012-05-08 2014-02-13 Onyx Therapeutics, Inc. Cyclodextrin complexation methods for formulating peptide proteasome inhibitors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070105786A1 (en) * 2005-11-09 2007-05-10 Proteolix, Inc. Compounds for enzyme inhibition
WO2007149512A2 (en) * 2006-06-19 2007-12-27 Proteolix, Inc. Peptide epoxyketones for pr0teas0me inhibition

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
EVAM. HUBER; MICHAEL BASLER; RICARDA SCHWAB; WOLFGANG HEINEMEYER; CHRISTOPHERJ. KIRK; MARCUS GROETTRUP; MICHAEL GROLL;: "Immuno- and Constitutive Proteasome Crystal Structures Reveal Differences in Substrate and Inhibitor Specificity", CELL, CELL PRESS, AMSTERDAM, NL, vol. 148, no. 4, 2 December 2011 (2011-12-02), AMSTERDAM, NL, pages 727 - 738, XP028458988, ISSN: 0092-8674, DOI: 10.1016/j.cell.2011.12.030 *
M. SCREEN, M. BRITTON, S. L. DOWNEY, M. VERDOES, M. J. VOGES, A. E. M. BLOM, P. P. GEURINK, M. D. P. RISSEEUW, B. I. FLOREA, W. A.: "Nature of Pharmacophore Influences Active Site Specificity of Proteasome Inhibitors", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 285, no. 51, 17 December 2010 (2010-12-17), pages 40125 - 40134, XP055099238, ISSN: 00219258, DOI: 10.1074/jbc.M110.160606 *
S. E. VERBRUGGE, Y. G. ASSARAF, B. A. C. DIJKMANS, G. L. SCHEFFER, M. AL, D. DEN UYL, R. OERLEMANS, E. T. CHAN, C. J. KIRK, G. J. : "Inactivating PSMB5 Mutations and P-Glycoprotein (Multidrug Resistance-Associated Protein/ATP-Binding Cassette B1) Mediate Resistance to Proteasome Inhibitors: Ex Vivo Efficacy of (Immuno)Proteasome Inhibitors in Mononuclear Blood Cells from Patients with Rheumatoid Arthritis", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 341, no. 1, 1 April 2012 (2012-04-01), pages 174 - 182, XP055129369, DOI: 10.1124/jpet.111.187542 *
TONY MUCHAMUEL, MICHAEL BASLER, MONETTE A AUJAY, ERIKA SUZUKI, KHALID W KALIM, CHRISTOPH LAUER, CATHERINE SYLVAIN, EILEEN R RING, : "A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis", NATURE MEDICINE, NATURE PUB. CO., vol. 15, no. 7, 1 July 2009 (2009-07-01), pages 781 - 787, XP055094218, ISSN: 10788956, DOI: 10.1038/nm.1978 *
WOOIN LEE, KYUNG BO KIM: "The Immunoproteasome: An Emerging Therapeutic Target", CURRENT TOPICS IN MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS, vol. 11, no. 23, 1 December 2011 (2011-12-01), pages 2923 - 2930, XP055129375, ISSN: 15680266, DOI: 10.2174/156802611798281348 *

Also Published As

Publication number Publication date
AU2019203282B2 (en) 2021-02-18
CA2904085C (en) 2021-07-06
IL241180A0 (en) 2015-11-30
JP6871310B2 (ja) 2021-05-12
DK2970225T3 (en) 2018-09-24
IL258297A (en) 2018-05-31
AU2019203282A1 (en) 2019-05-30
MX2015011770A (es) 2016-06-02
CN105164117B (zh) 2019-02-01
AU2014240122A1 (en) 2015-09-24
NZ711794A (en) 2020-12-18
AU2014240122B2 (en) 2019-02-14
SG11201507106PA (en) 2015-10-29
JP2016515127A (ja) 2016-05-26
KR20150131276A (ko) 2015-11-24
ES2687368T3 (es) 2018-10-24
CN105164117A (zh) 2015-12-16
EP2970225B1 (en) 2018-08-15
IL258297B (en) 2020-06-30
US9657057B2 (en) 2017-05-23
TW201446807A (zh) 2014-12-16
WO2014152127A1 (en) 2014-09-25
BR112015022856A2 (pt) 2017-07-18
MX362489B (es) 2019-01-21
CA2904085A1 (en) 2014-09-25
JO3326B1 (ar) 2019-03-13
BR112015022856A8 (pt) 2019-11-26
US20160031934A1 (en) 2016-02-04
EA201591752A1 (ru) 2016-02-29
EP2970225A1 (en) 2016-01-20
TWI662047B (zh) 2019-06-11
UY35455A (es) 2014-09-30
JP2019206531A (ja) 2019-12-05

Similar Documents

Publication Publication Date Title
PH12015502002B1 (en) Tripeptide epoxy ketone protease inhibitors
EA030957B1 (ru) Дипептидные и трипептидные эпоксикетонные ингибиторы протеазы
PH12017500367A1 (en) Compounds that inhibit mcl-1 protein
MX2015017964A (es) Inhibidores de bromodominio.
MA39986A (fr) Dérivés de purine en tant qu'inhibiteurs de cd73 pour le traitement du cancer
PH12016501790B1 (en) Pharmaceutical compositions of therapeutically active compounds
PH12016502355A1 (en) Pharmaceutical composition
PH12016501788B1 (en) Pharmaceutical compositions of therapeutically active compounds
MD4820C1 (ru) Замещенные дигидроизохинолиноновые соединения
MX2015010829A (es) Compuestos terapeuticos y sus usos.
NZ708016A (en) Lyophilized preparations of melphalan flufenamide
IN2013MU03583A (ru)
MX2016002580A (es) Combinacion de un inhibidor de alk y un inhibidor de cdk para el tratamiento de enfermedades celulares proliferativas.
EA201692481A1 (ru) Комбинация, содержащая глюкокортикоид и edo-s101
MX2017003216A (es) Uso de antagonistas de il-17 para inhibir la progresion del daño estructural en pacientes con artritis psoriasica.
PH12016502243A1 (en) Pharmaceutical compositions for treating infectious diseases
MY193996A (en) Tripeptide compound, preparation method therefor, and application thereof
PH12015500185B1 (en) Azaheterocycles as bir2 and/or bir3 inhibitors
MX2021003908A (es) Polipeptidos de accion prolongada y metodos para su produccion y administracion.
WO2018067638A3 (en) High mobility group b1 protein inhibitors

Legal Events

Date Code Title Description
MM4A Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)

Designated state(s): AM AZ BY KZ KG TJ TM