AR108919A1 - Proceso de preparación del inhibidor de inmunoproteasoma de péptido epoxicetona, y sus precursores - Google Patents

Proceso de preparación del inhibidor de inmunoproteasoma de péptido epoxicetona, y sus precursores

Info

Publication number
AR108919A1
AR108919A1 ARP170101808A ARP170101808A AR108919A1 AR 108919 A1 AR108919 A1 AR 108919A1 AR P170101808 A ARP170101808 A AR P170101808A AR P170101808 A ARP170101808 A AR P170101808A AR 108919 A1 AR108919 A1 AR 108919A1
Authority
AR
Argentina
Prior art keywords
compound
formula
methyloxiran
propanamido
oxopropan
Prior art date
Application number
ARP170101808A
Other languages
English (en)
Original Assignee
Kezar Life Sciences
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 Kezar Life Sciences filed Critical Kezar Life Sciences
Publication of AR108919A1 publication Critical patent/AR108919A1/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C229/36Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D301/00Preparation of oxiranes
    • C07D301/02Synthesis of the oxirane ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D303/00Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02Compounds containing oxirane rings
    • C07D303/12Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D303/00Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02Compounds containing oxirane rings
    • C07D303/12Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/32Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D303/00Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02Compounds containing oxirane rings
    • C07D303/38Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D303/46Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by amide or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Epoxy Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

En la presente se describen métodos para preparar [(2S,3R)-N-[(2S)-3-(ciclopent-1-en-1-il)-1-[(2R)-2-metiloxiran-2-il]-1-oxopropan-2-il]-3-hidroxi-3-(4-metoxifenil)-2-[(2S)-2-[2-(morfolin-4-il)acetamido]propanamido]propanamida (compuesto “G”) de fórmula (1) y sus precursores (compuesto “E” y compuesto “F”) de fórmula (2) y (3) respectivamente. Reivindicación 1: Un método de preparación de (2S,3R)-N-[(2S)-3-(ciclopent-1-en-1-il)-1-[(2R)-2-metiloxiran-2-il]-1-oxopropan-2-il]-3-hidroxi-3-(4-metoxifenil)-2-[(2S)-2-[2-(morfolin-4-il)acetamido]propanamido]propanamida (compuesto “G”) de fórmula (1) que comprende: (a) mezclar una base de amina terciaria y una suspensión de: (i) ácido (2S,3R)-3-hidroxi-3-(4-metoxifenil)-2-((S)-2-(2-morfolino-acetamido)propanamido)propanoico (compuesto “E”) de fórmula (2), y (ii) sal (S)-3-(ciclopent-1-en-1-il)-1-((R)-2-metiloxiran-2-il)-1-oxopropan-2-aminio (compuesto “F”) de fórmula (3), donde X⁻ es un contraión; en un solvente aprótico para formar una mezcla y (b) mezclar un agente de acoplamiento y la mezcla de la etapa (a) para formar el compuesto G de fórmula (1); donde la temperatura de cada etapa de mezclado se mantiene a -20ºC a 25ºC. Reivindicación 69: Una forma cristalina de ácido (2S,3R)-3-hidroxi-3-(4-metoxifenil)-2-((S)-2-(2-morfolinoacetamido)propanamido)propanoico (compuesto “E”) de fórmula (2) caracterizada por un patrón de difracción de rayos X de polvo que comprende picos en 6,2, 8,5, 9,7, 12,7, 13,7, 16,0, 16,9, 17,2, 18,4, 18,9, 19,2, 19,7, 22,5, 24,7, 25,4, 28,7, y 29,7 ± 0,2º 2q usando radiación Cu Ka. Reivindicación 70: Una forma cristalina de sal (S)-3-(ciclopent-1-en-1-il)-1-((R)-2-metiloxiran-2-il)-1-oxopropan-2-aminio (compuesto “F”) de fórmula (3) donde X⁻ es tosilato, caracterizada por un patrón de difracción de rayos X de polvo que comprende picos en 6,8, 7,1, 7,4, 20,3, 23,0, 23,6, 24,5, 29,3, y 31,2 ± 0,2º 2q usando radiación Cu Ka.
ARP170101808A 2016-06-29 2017-06-29 Proceso de preparación del inhibidor de inmunoproteasoma de péptido epoxicetona, y sus precursores AR108919A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201662356178P 2016-06-29 2016-06-29

Publications (1)

Publication Number Publication Date
AR108919A1 true AR108919A1 (es) 2018-10-10

Family

ID=59351085

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP170101808A AR108919A1 (es) 2016-06-29 2017-06-29 Proceso de preparación del inhibidor de inmunoproteasoma de péptido epoxicetona, y sus precursores

Country Status (17)

Country Link
US (3) US10781192B2 (es)
EP (2) EP3478669B1 (es)
JP (2) JP7065044B2 (es)
KR (2) KR102524751B1 (es)
CN (2) CN109641860B (es)
AR (1) AR108919A1 (es)
AU (1) AU2017290147B2 (es)
BR (1) BR112018077250A2 (es)
CA (1) CA3029418A1 (es)
CL (1) CL2018003873A1 (es)
CO (1) CO2019000866A2 (es)
EA (1) EA201990157A1 (es)
IL (2) IL302234A (es)
MX (1) MX2018016386A (es)
SG (1) SG11201811506UA (es)
TW (1) TWI751177B (es)
WO (1) WO2018005781A1 (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102524751B1 (ko) * 2016-06-29 2023-04-21 케자르 라이프 사이언스 펩티드 에폭시케톤 면역프로테아제 저해제 및 그 전구체의 제조 방법

Family Cites Families (26)

* 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
WO1998010779A1 (en) 1996-09-13 1998-03-19 New York University Method for treating parasitic diseases with proteasome inhibitors
CA2504933C (en) 2002-11-06 2012-10-16 Dana-Farber Cancer Institute, Inc. Methods and compositions for treating cancer using proteasome inhibitors
AU2006311584B2 (en) 2005-11-09 2012-03-08 Onyx Therapeutics, Inc. Compounds for enzyme inhibition
AU2007261345B2 (en) 2006-06-19 2012-02-23 Onyx Therapeutics, Inc. Peptide epoxyketones for proteasome inhibition
US7442830B1 (en) 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
KR20170125413A (ko) 2007-10-04 2017-11-14 오닉스 세라퓨틱스, 인크. 결정형 펩티드 에폭시 케톤 프로테아제 저해제 및 아미노산 케토-에폭시드의 합성
CN101525370A (zh) * 2008-03-06 2009-09-09 海南建邦制药科技有限公司 一种新型高效多肽合成缩合剂
CA2741312C (en) 2008-10-21 2020-10-27 Onyx Therapeutics, Inc. Combination therapy with peptide epoxyketones
TWI504598B (zh) 2009-03-20 2015-10-21 Onyx Therapeutics Inc 結晶性三肽環氧酮蛋白酶抑制劑
JP5919196B2 (ja) 2009-11-13 2016-05-18 オニキス セラピューティクス, インク.Onyx Therapeutics, Inc. 転移抑制のためのペプチドエポキシケトンの使用
MX2012011604A (es) 2010-04-07 2013-02-27 Onyx Therapeutics Inc Inhibidor de inmunoproteasoma de péptido epoxicetona cristalino.
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
WO2012151165A1 (en) 2011-05-02 2012-11-08 Gilead Sciences, Inc. Amorphous solid salts
KR20190137963A (ko) 2012-05-08 2019-12-11 오닉스 세라퓨틱스, 인크. 펩티드 프로테아좀 억제제 제제화를 위한 사이클로덱스트린 복합체화 방법
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
BR112015008160A2 (pt) 2012-10-11 2017-07-04 Hoffmann La Roche inibidores de imunoproteassoma de cetoamida
US20150266920A1 (en) 2012-10-12 2015-09-24 Hoff-Mann-La Roche Inc. Macrocyclic ketoamide immunoproteasome inhibitors
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
SG11201507106PA (en) * 2013-03-14 2015-10-29 Onyx Therapeutics Inc Dipeptide and tripeptide epoxy ketone protease inhibitors
AR095426A1 (es) * 2013-03-14 2015-10-14 Onyx Therapeutics Inc Inhibidores tripeptídicos de la epoxicetona proteasa
KR102365509B1 (ko) * 2013-03-14 2022-02-21 오닉스 세라퓨틱스, 인크. 트리펩타이드 에폭시 케톤 프로테이스 억제제
CN104710507B (zh) 2013-12-11 2018-08-14 深圳翰宇药业股份有限公司 一种卡非佐米的制备方法
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
KR102524751B1 (ko) * 2016-06-29 2023-04-21 케자르 라이프 사이언스 펩티드 에폭시케톤 면역프로테아제 저해제 및 그 전구체의 제조 방법

Also Published As

Publication number Publication date
WO2018005781A1 (en) 2018-01-04
CN109641860A (zh) 2019-04-16
SG11201811506UA (en) 2019-01-30
EP4296257A2 (en) 2023-12-27
JP7065044B2 (ja) 2022-05-11
CA3029418A1 (en) 2018-01-04
US20190194155A1 (en) 2019-06-27
EP4296257A3 (en) 2024-03-20
US10781192B2 (en) 2020-09-22
CN109641860B (zh) 2024-05-28
IL263771A (en) 2019-01-31
US20200407334A1 (en) 2020-12-31
AU2017290147B2 (en) 2021-09-09
JP7392031B2 (ja) 2023-12-05
KR102571568B1 (ko) 2023-08-25
CO2019000866A2 (es) 2019-04-12
US11498907B2 (en) 2022-11-15
JP2022105081A (ja) 2022-07-12
BR112018077250A2 (pt) 2019-04-02
JP2019527677A (ja) 2019-10-03
TWI751177B (zh) 2022-01-01
KR102524751B1 (ko) 2023-04-21
IL302234A (en) 2023-06-01
US11976053B2 (en) 2024-05-07
EP3478669B1 (en) 2023-08-30
US20230135100A1 (en) 2023-05-04
KR20190025945A (ko) 2019-03-12
EA201990157A1 (ru) 2019-05-31
IL263771B1 (en) 2023-05-01
TW201800397A (zh) 2018-01-01
MX2018016386A (es) 2019-09-09
CN118684637A (zh) 2024-09-24
CL2018003873A1 (es) 2019-06-21
IL263771B2 (en) 2023-09-01
EP3478669A1 (en) 2019-05-08
AU2017290147A1 (en) 2019-01-17
KR20230056798A (ko) 2023-04-27

Similar Documents

Publication Publication Date Title
EA202090658A1 (ru) Ингибиторы кэп-зависимой эндонуклеазы
TN2018000319A1 (en) Macrocyclic mcl1 inhibitors for treating cancer
EA201690959A1 (ru) Способ синтеза ингибитора индоламин-2,3-диоксигеназы
JP2017511305A5 (es)
EA201490453A1 (ru) Замещенные аналоги (e)-n-(1-фенилэтилиден)бензогидразида в качестве ингибиторов деметилазы гистонов
JP2015510886A5 (es)
CO6270323A2 (es) Formas solidas de acido (s)-2-amino-3-(4-(2-amino-6-((r)-2,2,2-trifluoro- 1-(3'-metoxibifenil-4-il)etoxi)pirimidin-4-il)fenil)propanoico y metodos para su uso
BR112015014222A2 (pt) composto, composição farmacêutica, uso de um composto, método para o tratamento de anemia e composição farmacêutica
AR055647A1 (es) Derivados de n-sulfonilpirrol como inhibidores de hdac, sus sales cristalinas, metodos para su preparacion y polimorfos de los mismos, composiciones farmaceuticas que los contienen y su uso en combinacion con agentes anticancer para el tratamiento de la neoplasia.
CU24330B1 (es) Derivados del ácido 4-((1,1) bifenil-4-il)-3-(3-fosfonopropanamido) butanoico, activos como inhibidores de nep (endopeptidasa neutral)
MX2019008626A (es) Derivados de 1,1,1-trifluoro-3-hidroxipropan-2-ilcarbamato como inhibidores de monoacilglicerol lipasa (magl).
EA201691538A1 (ru) Способ получения солей вортиоксетина
AR074128A1 (es) Derivados de 4-[2-(2-fluorofenoximetil)fenil] piperidina, composiciones farmaceuticas que los contienen, metodo de preparacion, compuestos intermediarios de dicho proceso y uso de los mismos para el tratamiento de dolores neuropaticos, mal de alzheimer y otras enfermedades relacionadas con el snc.
AR119614A1 (es) Formas en estado sólido de (s)-2-(((s)-6,8-diflúor-1,2,3,4-tetrahidronaftalen-2-il)amino)-n-(1-(2-metil-1-(neopentilamino)propan-2-il)-1h-imidazol-4-il)pentanamida y usos de la misma
HRP20210503T1 (hr) Kristalni oblici soli tapentadola i postupci za njihovu pripremu
AR108919A1 (es) Proceso de preparación del inhibidor de inmunoproteasoma de péptido epoxicetona, y sus precursores
CL2018002344A1 (es) Proceso para preparar compuestos de 7h-pirrolo[2,3-d]pirimidina
JP2019501948A5 (es)
MX2018006904A (es) Derivados de fumagilol y polimorfos de los mismos.
AR074593A1 (es) Benzotiazol amidas para la deteccion del peptido beta amiloide
MX2017011392A (es) P-toluensulfonato para inhibidor de mek cinasa, y su forma de cristal y su metodo de preparacion.
RU2015113961A (ru) Азаиндолины
BR112013031201A2 (pt) derivados de sulfonamida heterocíclicos, composição farmacêutica os compreendendo, uso, processo para a fabricação de (r)-n-(4,5-difluoro-6-((2-fluoro-4-iodofenil)amino)benzofuran-7-il)-1-(2,3-di-idroxipropil)ciclopropano-5 1-sulfonamida e kit
RU2018122012A (ru) БИС-пиридазиновые соединения и их применение в лечении рака
BRPI0806411B8 (pt) processo para a preparação de um composto e compostos