ME02462B - Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto- epoksida - Google Patents

Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto- epoksida

Info

Publication number
ME02462B
ME02462B MEP-2016-128A MEP12816A ME02462B ME 02462 B ME02462 B ME 02462B ME P12816 A MEP12816 A ME P12816A ME 02462 B ME02462 B ME 02462B
Authority
ME
Montenegro
Prior art keywords
crystalline
crystalline compound
salt
epoxides
synthesis
Prior art date
Application number
MEP-2016-128A
Other languages
English (en)
French (fr)
Inventor
Pasit Phiasivongsa
Louis C Sehl
William Dean Fuller
Guy J Laidig
Original Assignee
Onyx Therapeutics Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39941499&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02462(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Onyx Therapeutics Inc filed Critical Onyx Therapeutics Inc
Publication of ME02462B publication Critical patent/ME02462B/me

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a 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
    • C07K5/10—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
    • 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
    • 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
    • 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
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • 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
    • A61P33/00—Antiparasitic 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
    • 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
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C3/00—Fire prevention, containment or extinguishing specially adapted for particular objects or places
    • A62C3/002—Fire prevention, containment or extinguishing specially adapted for particular objects or places for warehouses, storage areas or other installations for storing goods
    • A62C3/004—Fire prevention, containment or extinguishing specially adapted for particular objects or places for warehouses, storage areas or other installations for storing goods for freezing warehouses and storages
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C35/00—Permanently-installed equipment
    • A62C35/58—Pipe-line systems
    • A62C35/68—Details, e.g. of pipes or valve systems
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C37/00—Control of fire-fighting equipment
    • A62C37/08—Control of fire-fighting equipment comprising an outlet device containing a sensor, or itself being the sensor, i.e. self-contained sprinklers
    • A62C37/10—Releasing means, e.g. electrically released
    • A62C37/11—Releasing means, e.g. electrically released heat-sensitive
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
    • C07C53/16—Halogenated acetic acids
    • C07C53/18—Halogenated acetic acids containing fluorine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/02—Synthesis of the oxirane ring
    • C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
    • 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
    • C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/30—Extraction; Separation; Purification by precipitation
    • C07K1/306—Extraction; Separation; Purification by precipitation by crystallization
    • 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
    • C07K5/10—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
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C35/00—Permanently-installed equipment
    • A62C35/58—Pipe-line systems
    • A62C35/60—Pipe-line systems wet, i.e. containing extinguishing material even when not in use
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C35/00—Permanently-installed equipment
    • A62C35/58—Pipe-line systems
    • A62C35/62—Pipe-line systems dry, i.e. empty of extinguishing material when not in use
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62C—FIRE-FIGHTING
    • A62C37/00—Control of fire-fighting equipment
    • A62C37/08—Control of fire-fighting equipment comprising an outlet device containing a sensor, or itself being the sensor, i.e. self-contained sprinklers
    • A62C37/10—Releasing means, e.g. electrically released
    • A62C37/11—Releasing means, e.g. electrically released heat-sensitive
    • A62C37/14—Releasing means, e.g. electrically released heat-sensitive with frangible vessels

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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Emergency Management (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Business, Economics & Management (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Analytical Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Psychiatry (AREA)
  • Operations Research (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)

Claims (12)

1. Kristalno jedinjenje koje ima strukturu Formule (II)
2. Kristalno jedinjenje prema patentnom zahtevu 1, koje ima tačku topljenja od 211 do 213°C.
3. Kristalno jedinjenje prema bilo kom od patentnih zahteva 1 ili 2 koje ima XRPD značajan obrazac kao što je prikazano na Slici 2:
4. Kristalno jedinjenje prema bilo kom od patentnih zahteva 1 ili 2 koje ima 2θ vrednosti 6,10; 8,10; 9,32; 10,10; 11,00; 12,14; 122,50; 13,64; 13,94; 17,14; 17,52; 18,44; 20,38; 21,00; 22,26; 23,30; 24,66; 25,98; 26,02; 27,84; 28,00; 28,16; 29,98; 30,46; 32,98; 33,22; 34,52; 39,46.
5. Kristalna so jedinjenja koje ima strukturu Formule (II) gde je so citratna so.
6. Kristalna so prema patentnom zahtevu 5, koje ima tačku topljenja od 184 do 188°C.
7. Kristalna so prema bilo kom od patentnih zahteva 5 ili 6, koje ima XRPD značajan obrazac kao što je prikazano na Slici 12:
8. Kristalna so prema bilo kom od patentnih zahteva od 5 do 7, koja ima 2θ vrednosti 4,40; 7,22; 9,12; 12,36; 13,35; 14,34; 15,54; 16,14; 16,54; 17,00; 18,24; 18,58; 19,70; 19,90; 20,30; 20,42; 21,84; 22,02; 23,34; 23,84; 24,04; 24,08; 24,48; 24,76; 25,48; 26,18; 28,14; 28,20; 28,64; 29,64; 31,04; 31,84; 33,00; 33,20; 34,06; 34,30; 34,50; 35,18; 37,48; 37,90; 39,48.
9. Kristalno jedinjenje prema bilo kom od patentnih zahteva od 1 do 4 za primenu u medicini.
10. Kristalno jedinjenje za korišćenje prema patentnom zahtevu 9 za primenu u tretiranju bolesti ili stanja odabranih iz kancera, autoimunih bolesti, stanja povezanih sa graftom ili transplantacijom, neurodegenerativnih bolesti, stanja povezanih sa fibrozom, stanja povezanih sa ishemijama, infekcija (virusna, parazitska ili prokariotska) i bolesti povezane sa gubitkom kostiju.
11. Kristalno jedinjenje za korišćenje prema patentnom zahtevu 10, gde je bolest ili stanje kancer i gde je kancer multipli mijelom.
12. Farmaceutski sastav koji obuhvata kristalno jedinjenje bilo kog od patentnih zahteva 1 do 4 i farmaceutski prihvatljiv nosač.
MEP-2016-128A 2007-10-04 2008-10-03 Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto- epoksida ME02462B (me)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US99761307P 2007-10-04 2007-10-04
US898707P 2007-12-20 2007-12-20
EP08834964.2A EP2207791B2 (en) 2007-10-04 2008-10-03 Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
PCT/US2008/011443 WO2009045497A1 (en) 2007-10-04 2008-10-03 Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides

Publications (1)

Publication Number Publication Date
ME02462B true ME02462B (me) 2017-02-20

Family

ID=39941499

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-2016-128A ME02462B (me) 2007-10-04 2008-10-03 Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto- epoksida

Country Status (35)

Country Link
US (3) US8367617B2 (me)
EP (3) EP2612856B8 (me)
JP (2) JP5734656B2 (me)
KR (5) KR20170125413A (me)
CN (1) CN101883779B (me)
AR (1) AR068681A1 (me)
AU (1) AU2008307510A1 (me)
CA (1) CA2701778C (me)
CL (2) CL2008002966A1 (me)
CO (1) CO6270366A2 (me)
CR (1) CR11364A (me)
CY (1) CY1117710T1 (me)
DK (1) DK2207791T4 (me)
DO (1) DOP2010000095A (me)
EA (2) EA018973B1 (me)
EC (1) ECSP10010103A (me)
ES (2) ES2578905T5 (me)
HR (1) HRP20160808T4 (me)
HU (1) HUE029665T2 (me)
IL (5) IL204890A0 (me)
MA (1) MA31831B1 (me)
ME (1) ME02462B (me)
MX (1) MX2010003732A (me)
MY (2) MY173938A (me)
NZ (2) NZ584814A (me)
PH (1) PH12013501377A1 (me)
PL (1) PL2207791T5 (me)
PT (1) PT2207791T (me)
RS (1) RS54847B2 (me)
SA (1) SA08290624B1 (me)
SG (2) SG185994A1 (me)
SI (1) SI2207791T2 (me)
TW (1) TWI501773B (me)
WO (1) WO2009045497A1 (me)
ZA (1) ZA201002770B (me)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8198270B2 (en) * 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
JP5616569B2 (ja) 2004-04-15 2014-10-29 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． 酵素阻害のための化合物
EP1758921A2 (en) 2004-05-10 2007-03-07 Proteolix, Inc. Compounds for proteasome enzyme inhibition
ES2628620T3 (es) 2005-11-09 2017-08-03 Onyx Therapeutics, Inc. Compuesto para inhibición de enzimas
PT2041158E (pt) 2006-06-19 2013-07-17 Onyx Therapeutics Inc Péptido epoxicetonas para inibição de proteassoma
MY173938A (en) 2007-10-04 2020-02-27 Onyx Therapeutics Inc Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
US7635773B2 (en) 2008-04-28 2009-12-22 Cydex Pharmaceuticals, Inc. Sulfoalkyl ether cyclodextrin compositions
AU2009308516B2 (en) 2008-10-21 2016-08-25 Onyx Therapeutics, Inc. Combination therapy with peptide epoxyketones
AR075899A1 (es) * 2009-03-20 2011-05-04 Onyx Therapeutics Inc Tripeptidos epoxicetonas cristalinos inhibidores de proteasa
US8853147B2 (en) 2009-11-13 2014-10-07 Onyx Therapeutics, Inc. Use of peptide epoxyketones for metastasis suppression
US9359398B2 (en) 2010-03-01 2016-06-07 Onyx Therapeutics, Inc. Compounds for immunoproteasome inhibition
NZ602872A (en) * 2010-04-07 2014-05-30 Onyx Therapeutics Inc Crystalline peptide epoxyketone immunoproteasome inhibitor
JO3283B1 (ar) 2011-04-26 2018-09-16 Sanofi Sa تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI)
EP2814849B8 (en) 2012-02-15 2020-03-04 CyDex Pharmaceuticals, Inc. Manufacturing process for cyclodextrin derivatives
AU2013226073B2 (en) 2012-02-28 2016-05-05 Cydex Pharmaceuticals, Inc. Alkylated cyclodextrin compositions and processes for preparing and using the same
LT2662094T (lt) * 2012-05-08 2024-07-10 Onyx Therapeutics, Inc. Ciklodekstrino kompleksodaros metodai, skirti peptidų proteasomos komponavimui
JP2015516416A (ja) * 2012-05-08 2015-06-11 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． ペプチドプロテアソーム阻害剤を調合するためのシクロデキストリン錯体形成法
IN2014DN10758A (me) 2012-06-29 2015-09-04 Nissan Chemical Ind Ltd
UY34897A (es) 2012-07-09 2014-01-31 Onyx Therapeutics Inc Profarmacos de inhibidores peptidicos de expoxi cetona proteasa
CN109180780B (zh) * 2012-07-26 2022-03-18 圣特莱国际公司 多肽环氧酮化合物
WO2014018807A1 (en) * 2012-07-26 2014-01-30 Centrax International, Inc. Peptide epoxyketone compounds
US9636376B2 (en) * 2012-09-11 2017-05-02 Innopharma, Inc. Stable compositions of peptide epoxy ketones
EA032006B1 (ru) 2012-10-22 2019-03-29 Сидекс Фармасьютикалс, Инк. Композиции алкилированного циклодекстрина и способы их получения и применения
TW201422255A (zh) * 2012-10-24 2014-06-16 Onyx Therapeutics Inc 用於蛋白酶體抑制劑之調整釋放製劑
US8906853B2 (en) 2012-11-28 2014-12-09 Enanta Pharmaceuticals, Inc. [N-Me-4-hydroxyleucine]-9-cyclosporin analogues for treatment and prevention of hepatitis C infection
US9795638B1 (en) * 2013-03-16 2017-10-24 BioDlogics, LLC Cardiothoracic construct and methods of use
CA2918530C (en) 2013-07-19 2023-10-03 Onyx Therapeutics, Inc. Peptide epoxyketone proteasome inhibitors in combination with pim kinase inhibitors for treatment of cancers
CN103360348B (zh) * 2013-07-25 2015-06-24 苏州鹏旭医药科技有限公司 一种Carfilzomib中间体及其制备方法和制备Carfilzomib的方法
CA2922210A1 (en) * 2013-09-06 2015-03-12 Sandoz Ag Stereoselective synthesis of diols and triols by mannich reaction and their use in the synthesis of carfilzomib
US20160215016A1 (en) * 2013-09-06 2016-07-28 Sandoz Ag Synthesis of peptide epoxy ketones
WO2015121769A1 (en) 2014-02-13 2015-08-20 Ranbaxy Laboratories Limited Process for the preparation of methyl n-[(benzyloxy)-carbonyl]-l-leucyl-l-phenylalaninate
AU2015289124B2 (en) 2014-07-18 2021-03-11 Sanofi Method for predicting the outcome of a treatment with aflibercept of a patient suspected to suffer from a cancer
CN104230857A (zh) * 2014-08-19 2014-12-24 上海皓元生物医药科技有限公司 卡非佐米(Carfilzomib)的中间体化合物的制备方法及其中间体化合物
US10851184B2 (en) 2014-08-22 2020-12-01 Cydex Pharmaceuticals, Inc. Fractionated alkylated cyclodextrin compositions and processes for preparing and using the same
WO2016046843A1 (en) * 2014-09-24 2016-03-31 Biophore India Pharmaceuticals Pvt. Ltd. Process for the preparation of (s)-4-methyl-n-((s)-1-(((s)-4-methyl-1-((r)-2-methyloxiran-2-yl)-1-oxo pentan-2-yl) amino)-1-oxo-3-phenylpropan-2-yl)-2-((s)-2-(2-morpholinoacetamido)-4-phenylbutanamido) pentanamide
WO2016069479A1 (en) * 2014-10-27 2016-05-06 Apicore Us Llc Methods of making carfilzomib and intermediates thereof
US10253066B2 (en) 2014-12-02 2019-04-09 Fresenius Kabi Oncology Limited Process for purification of Carfilzomib
US10301353B2 (en) 2014-12-31 2019-05-28 Dr. Reddy's Laboratories Limited Co-crystal of carfilzomib with maleic acid and process for the preparation of pure carfilzomib
CN105985408B (zh) * 2015-02-12 2020-06-26 正大天晴药业集团股份有限公司 一种卡非佐米的纯化方法
CN104844540A (zh) * 2015-05-18 2015-08-19 上海凯欣生物医药科技有限公司 一种(2s)-2-氨基-4-甲基-1-[(2r)-2-甲基环氧乙烷基]-1-戊酮三氟乙酸盐的新晶型及其制备方法
WO2016185450A1 (en) * 2015-05-21 2016-11-24 Laurus Labs Private Limited An improved processes for the preparation of carfilzomib or pharmaceutically acceptable salts thereof
CN104961799B (zh) * 2015-06-19 2021-05-11 重庆医药工业研究院有限责任公司 一种卡非佐米晶型a及其制备方法
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
CN105294501B (zh) * 2015-08-21 2017-09-29 上海应用技术学院 一种卡非佐米中间体化合物的制备方法
WO2017098532A1 (en) 2015-12-11 2017-06-15 Mylan Laboratories Limited Crystalline and amorphous forms of carfilzomib
TWI759301B (zh) 2016-05-24 2022-04-01 美商安美基公司 聚乙二醇化卡非佐米化合物
EA201990154A1 (ru) 2016-06-29 2019-06-28 Кезар Лайф Сайнсиз Ингибитор иммунопротеасомы на основе кристаллических солей пептидных эпоксикетонов
IL302234A (en) 2016-06-29 2023-06-01 Kezar Life Sciences Process of preparing a peptide epoxyketone immunoproteasome inhibitor, and precursors thereof
WO2018024645A1 (en) 2016-08-02 2018-02-08 Synthon B.V. Process for making carfilzomib
EP3494108B1 (en) 2016-08-05 2020-10-28 Amgen Inc. Synthesis of (s)-2-amino-4-methyl-1-((r)-2-methyloxirane-2-yl)-pentan-1-one and pharmaceutically acceptable salts thereof
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
US11241502B2 (en) 2017-11-16 2022-02-08 Amgen Inc. Stable compositions of pegylated carfilzomib compounds
CN113200943B (zh) * 2021-04-23 2024-07-26 湖南华腾制药有限公司 一种卡非佐米中间体的制备方法
CN114195741A (zh) * 2021-12-28 2022-03-18 南京格亚医药科技有限公司 一种卡非佐米关键中间体异构体的制备方法
CN116023347A (zh) * 2022-10-09 2023-04-28 无锡紫杉药业股份有限公司 一种卡非佐米侧链的异构体制备方法
WO2025035020A2 (en) 2023-08-09 2025-02-13 Amgen Inc. Methods of using carfilzomib
CN120040313B (zh) * 2025-04-24 2025-07-15 山东金城柯瑞化学有限公司 泊沙康唑起始原料sm3的制备方法

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
US4990448A (en) 1989-08-04 1991-02-05 Bristol-Myers Company Bu-4061T
US5071957A (en) * 1989-08-04 1991-12-10 Bristol-Myers Company Antibiotic BU-4061T
KR0166088B1 (ko) * 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
US5376645A (en) * 1990-01-23 1994-12-27 University Of Kansas Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
AU661270B2 (en) 1990-03-05 1995-07-20 Cephalon, Inc. 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
AU4499697A (en) 1996-09-13 1998-04-02 New York University Method for treating parasitic diseases with proteasome inhibitors
SI0932617T1 (en) 1996-10-18 2002-06-30 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease
SK286105B6 (sk) * 1996-10-18 2008-03-05 Vertex Pharmaceuticals Incorporated Inhibítory serínových proteáz, najmä NS3 proteázyvírusu hepatitídy C, farmaceutická kompozícia a použitie
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
ATE253941T1 (de) * 1997-06-13 2003-11-15 Cydex Inc Zusammensetzung mit erhöhter lagerstabilität enthaltend cyclodextrin und wirkstoffe oder wirkstoff-vorstufen, die in wasserunlösliche komponenten zersetzt werden
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
US6838436B1 (en) * 1998-07-10 2005-01-04 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
US6204257B1 (en) * 1998-08-07 2001-03-20 Universtiy Of Kansas Water soluble prodrugs of hindered alcohols
CA2347275C (en) * 1998-10-20 2010-03-09 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
EP1221962A2 (en) 1999-10-20 2002-07-17 Osteoscreen, Inc. Inhibitors of proteasomal activity for stimulating bone and hair growth
EP1326632B1 (de) * 2000-10-12 2006-09-06 Viromics Gmbh Proteasome inhibitoren zur behandlung von hepatitis-virus infektionen
AU2002243646B2 (en) 2001-01-25 2006-06-22 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Formulation of boronic acid compounds
PL367287A1 (en) * 2001-05-21 2005-02-21 Alcon, Inc. Use of proteasome inhibitors to treat dry eye disorders
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
CA2481306A1 (en) * 2002-04-09 2003-10-23 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
AU2003249682A1 (en) * 2002-06-03 2003-12-19 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
AU2003256847A1 (en) 2002-07-26 2004-02-16 Advanced Research And Technology Institute At Indiana University Method of treating cancer
US6749743B1 (en) * 2002-10-04 2004-06-15 Zabel Industries International, Ltd. Fuel diverter for a recirculating wastewater treatment system
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
TW200418791A (en) * 2003-01-23 2004-10-01 Bristol Myers Squibb Co Pharmaceutical compositions for inhibiting proteasome
DE602004017847D1 (de) 2003-04-08 2009-01-02 Novartis Ag Feste pharmazeutische darreichungsformen mit einem s1p rezeptoragonisten und einem zuckeralkohol
CA2528120A1 (en) * 2003-06-10 2005-01-20 The J. David Gladstone Institutes Methods for treating lentivirus infections
US7012063B2 (en) * 2003-06-13 2006-03-14 Children's Medical Center Corporation Reducing axon degeneration with proteasome inhibitors
EP3238708A1 (en) 2003-12-31 2017-11-01 CyDex Pharmaceuticals, Inc. Inhalant formulation containing cyclodextrin and corticosteroid
GB0400804D0 (en) 2004-01-14 2004-02-18 Innoscience Technology Bv Pharmaceutical compositions
US7232818B2 (en) * 2004-04-15 2007-06-19 Proteolix, Inc. Compounds for enzyme inhibition
US8198270B2 (en) * 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
JP5616569B2 (ja) 2004-04-15 2014-10-29 オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． 酵素阻害のための化合物
CN101006098B (zh) * 2004-04-15 2014-10-29 欧尼斯治疗公司 用于抑制蛋白酶体酶的化合物
AU2005243140A1 (en) 2004-05-10 2005-11-24 Proteolix, Inc. Synthesis of amino acid keto-epoxides
EP1758921A2 (en) * 2004-05-10 2007-03-07 Proteolix, Inc. Compounds for proteasome enzyme inhibition
CN101044157B (zh) * 2004-08-06 2011-07-13 普罗特奥里克斯公司 用于抑制蛋白酶体的化合物
EP1805208A2 (en) * 2004-10-20 2007-07-11 Proteolix, Inc. Labeled compounds for proteasome inhibition
JP4990155B2 (ja) * 2004-12-07 2012-08-01 プロテオリックス， インコーポレイテッド プロテアソームを阻害するための組成物
US7468383B2 (en) 2005-02-11 2008-12-23 Cephalon, Inc. Proteasome inhibitors and methods of using the same
WO2006099261A2 (en) 2005-03-11 2006-09-21 The University Of North Carolina At Chapel Hill Potent and specific immunoproteasome inhibitors
US7998938B2 (en) 2005-04-15 2011-08-16 Geron Corporation Cancer treatment by combined inhibition of proteasome and telomerase activities
GT200600350A (es) 2005-08-09 2007-03-28 Formulaciones líquidas
ES2628620T3 (es) * 2005-11-09 2017-08-03 Onyx Therapeutics, Inc. Compuesto para inhibición de enzimas
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
PT2041158E (pt) 2006-06-19 2013-07-17 Onyx Therapeutics Inc Péptido epoxicetonas para inibição de proteassoma
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
CA2676387A1 (en) 2007-01-23 2008-07-31 Gloucester Pharmaceuticals, Inc. Combination therapy
WO2008140782A2 (en) 2007-05-10 2008-11-20 Proteolix, Inc. Compounds for enzyme inhibition
JP5261488B2 (ja) 2007-08-06 2013-08-14 ミレニアム ファーマシューティカルズ， インコーポレイテッド プロテアソーム阻害剤
US7442830B1 (en) 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
MY173938A (en) 2007-10-04 2020-02-27 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
CN107266480A (zh) 2008-06-17 2017-10-20 米伦纽姆医药公司 硼酸酯化合物及其医药组合物
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.
AU2009308516B2 (en) 2008-10-21 2016-08-25 Onyx Therapeutics, Inc. Combination therapy with peptide epoxyketones
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
US8853147B2 (en) 2009-11-13 2014-10-07 Onyx Therapeutics, Inc. Use of peptide epoxyketones for metastasis suppression
US9359398B2 (en) 2010-03-01 2016-06-07 Onyx Therapeutics, Inc. Compounds for immunoproteasome inhibition
MA34169B1 (fr) 2010-03-31 2013-04-03 Millennium Pharm Inc Dérivés d'acide 1-amino-2-cyclopropyléthylboronique
NZ602872A (en) 2010-04-07 2014-05-30 Onyx Therapeutics Inc Crystalline peptide epoxyketone immunoproteasome inhibitor

Also Published As

Publication number Publication date
ES2578905T5 (es) 2020-03-18
KR20160086980A (ko) 2016-07-20
CL2012003441A1 (es) 2013-12-13
JP5734656B2 (ja) 2015-06-17
WO2009045497A1 (en) 2009-04-09
PL2207791T3 (pl) 2016-10-31
MA31831B1 (fr) 2010-11-01
SG185994A1 (en) 2012-12-28
HK1149573A1 (en) 2011-10-07
EP2612865A2 (en) 2013-07-10
CL2008002966A1 (es) 2010-06-25
EA201070429A1 (ru) 2010-10-29
CR11364A (es) 2010-07-09
EA201201476A1 (ru) 2013-07-30
MX2010003732A (es) 2010-08-09
EP2207791B1 (en) 2016-04-13
IL238248A (en) 2016-12-29
DK2207791T3 (en) 2016-07-25
DK2207791T4 (da) 2019-10-07
JP2010540637A (ja) 2010-12-24
NZ598436A (en) 2014-03-28
CN101883779B (zh) 2014-08-06
NZ584814A (en) 2012-03-30
AR068681A1 (es) 2009-11-25
RS54847B2 (sr) 2019-09-30
KR20100088664A (ko) 2010-08-10
EP2612856A2 (en) 2013-07-10
IL204890A0 (en) 2010-11-30
ES2684340T3 (es) 2018-10-02
KR20150131405A (ko) 2015-11-24
CA2701778A1 (en) 2009-04-09
IL238247A (en) 2016-05-31
HRP20160808T4 (hr) 2020-05-29
EP2612856B8 (en) 2018-10-17
US20130150289A1 (en) 2013-06-13
EP2612865A3 (en) 2014-03-19
CY1117710T1 (el) 2017-05-17
PT2207791T (pt) 2016-07-12
US20090105156A1 (en) 2009-04-23
EP2612856A3 (en) 2014-03-26
CO6270366A2 (es) 2011-04-20
SG10201902704TA (en) 2019-04-29
SI2207791T2 (sl) 2019-09-30
TW200924789A (en) 2009-06-16
RS54847B1 (sr) 2016-10-31
EA018973B1 (ru) 2013-12-30
IL223698A0 (en) 2013-02-03
MY166950A (en) 2018-07-25
PH12013501377A1 (en) 2014-08-27
EP2207791A1 (en) 2010-07-21
CN101883779A (zh) 2010-11-10
MY173938A (en) 2020-02-27
EP2207791B2 (en) 2019-08-07
JP2015163619A (ja) 2015-09-10
ZA201002770B (en) 2022-03-30
SA08290624B1 (ar) 2013-08-18
US20130150290A1 (en) 2013-06-13
SI2207791T1 (sl) 2016-07-29
EP2612856B1 (en) 2018-07-18
DOP2010000095A (es) 2010-06-30
AU2008307510A1 (en) 2009-04-09
IL238246A (en) 2016-05-31
HUE029665T2 (en) 2017-03-28
KR20170040374A (ko) 2017-04-12
TWI501773B (zh) 2015-10-01
ES2578905T3 (es) 2016-08-02
ECSP10010103A (es) 2010-06-29
CA2701778C (en) 2018-09-11
US8921583B2 (en) 2014-12-30
PL2207791T5 (pl) 2020-07-27
EA024437B1 (ru) 2016-09-30
US8367617B2 (en) 2013-02-05
HRP20160808T1 (hr) 2016-08-26
KR20170125413A (ko) 2017-11-14
US8921324B2 (en) 2014-12-30

Similar Documents

Publication Publication Date Title
ME02462B (me) Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto- epoksida
FI107733B (fi) Menetelmä sekä välituote trombiini-inhibiittorivaikutuksen omaavien dipeptidijohdannaisten valmistamiseksi
CA2613112C (en) Hcv inhibitors
NZ603232A (en) Nucleoside phosphoramidates
CA2724785C (en) Selective caspase inhibitors and uses thereof
WO2011012746A2 (es) Compuestos inhibidores de apaf-1
ME02536B (me) Antiviralna jedinjenja
WO2010033444A8 (en) Crystalline forms of a 2-thiazolyl- 4-quinolinyl-oxy derivative, a potent hcv inhibitor
CA2473070A1 (en) Proline compounds as ns3-serine protease inhibitors for use in treatment of hepatites c virus infection
NZ596922A (en) Thiophene analogues for the treatment or prevention of Flavivirus infections
WO2010000372A3 (en) New drug for inhibiting aggregation of proteins involved in diseases linked to protein aggregation and/or neurodegenerative diseases
ECSP034850A (es) Sal citrato de 5, 8, 14-triazatetraciclo [10.3.1.02,11.04,9] hexadeca-2 (11),3,5,7,9-pentaeno y composiciones farmaceuticas de la misma
CL2008002330A1 (es) Compuestos derivados de alcoholes de 1-fenil-2-piridinilalquilo, inhibidores de la fosfodiesterasa 4 (pde4); proceso de preparacion de dichos compuestos; composiciones farmaceuticas que los contienen; y su uso para preparar medicamentos utiles en la prevencion o tratamiento de asma, bronquitis cronica y epoc.
JP2014510746A5 (me)
SK899A3 (en) Thrombin inhibitors
JP2014520077A5 (me)
CN106699690A (zh) 一种具有酰基哌嗪基侧链的截短侧耳素衍生物及其制备方法和用途
US20160362400A1 (en) Avanafil preparation method
CN101759601B (zh) 利用过渡金属配合物制备手性α-非天然氨基酸的方法
CN101544688B (zh) 环五肽细胞凋亡酶抑制剂及其制备方法
WO2010133000A1 (en) Selective caspase inhibitors and uses thereof
Grimm et al. Solid phase synthesis of selective caspase-3 peptide inhibitors
CN110437157A (zh) 一种芳基嘧啶类截短侧耳素衍生物及其制备方法和用途
CN105175406B (zh) Hcv抑制剂的中间体以及由其制备hcv抑制剂的方法
CN104311452B (zh) 腈基萘环的丁二酸酰胺衍生物、其制备方法及用途