BRPI0924084B1 - Derivados de pirazina e composição farmacêutica que os compreende - Google Patents

Derivados de pirazina e composição farmacêutica que os compreende Download PDF

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Publication number
BRPI0924084B1
BRPI0924084B1 BRPI0924084-5A BRPI0924084A BRPI0924084B1 BR PI0924084 B1 BRPI0924084 B1 BR PI0924084B1 BR PI0924084 A BRPI0924084 A BR PI0924084A BR PI0924084 B1 BRPI0924084 B1 BR PI0924084B1
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BR
Brazil
Prior art keywords
compound
amino
phenyl
mmol
aliphatic
Prior art date
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BRPI0924084-5A
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English (en)
Portuguese (pt)
Inventor
Jean-Damien Charrier
Steven Durrant
David Kay
Ronald Knegtel
Somhairle MacCormick
Michael Mortimore
Michael O'Donnell
Joanne Pinder
Alistair Rutherford
Anisa Nizarali Virani
Stephen Young
Philip Michael Reaper
Original Assignee
Vertex Pharmaceuticals Incorporated
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Publication date
Application filed by Vertex Pharmaceuticals Incorporated filed Critical Vertex Pharmaceuticals Incorporated
Publication of BRPI0924084A2 publication Critical patent/BRPI0924084A2/pt
Publication of BRPI0924084B1 publication Critical patent/BRPI0924084B1/pt

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20Nitrogen atoms
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    • 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
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
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    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
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    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D401/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
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    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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    • 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
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    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S507/00Earth boring, well treating, and oil field chemistry
    • Y10S507/939Corrosion inhibitor

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
BRPI0924084-5A 2008-12-19 2009-12-18 Derivados de pirazina e composição farmacêutica que os compreende BRPI0924084B1 (pt)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US13942908P 2008-12-19 2008-12-19
US13942008P 2008-12-19 2008-12-19
US13942608P 2008-12-19 2008-12-19
US13942408P 2008-12-19 2008-12-19
US61/139,426 2008-12-19
US61/139,429 2008-12-19
US61/139,424 2008-12-19
US61/139,420 2008-12-19
US18179409P 2009-05-28 2009-05-28
US61/181,794 2009-05-28
US21910009P 2009-06-22 2009-06-22
US61/219,100 2009-06-22
PCT/US2009/068827 WO2010071837A1 (en) 2008-12-19 2009-12-18 Pyrazine derivatives useful as inhibitors of atr kinase

Publications (2)

Publication Number Publication Date
BRPI0924084A2 BRPI0924084A2 (pt) 2020-11-10
BRPI0924084B1 true BRPI0924084B1 (pt) 2021-12-21

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ID=41683104

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BRPI0924084-5A BRPI0924084B1 (pt) 2008-12-19 2009-12-18 Derivados de pirazina e composição farmacêutica que os compreende

Country Status (29)

Country Link
US (7) US8841308B2 (OSRAM)
EP (3) EP3354650B1 (OSRAM)
JP (5) JP5753093B2 (OSRAM)
KR (3) KR101755216B1 (OSRAM)
CN (4) CN106496209B (OSRAM)
AR (1) AR074822A1 (OSRAM)
AU (3) AU2009327357C1 (OSRAM)
BR (1) BRPI0924084B1 (OSRAM)
CA (2) CA2747252C (OSRAM)
CY (1) CY1120002T1 (OSRAM)
DK (2) DK2376485T3 (OSRAM)
ES (2) ES2663222T3 (OSRAM)
HR (2) HRP20180385T1 (OSRAM)
HU (1) HUE036068T2 (OSRAM)
IL (3) IL213613A (OSRAM)
LT (2) LT2376485T (OSRAM)
MX (1) MX2011006503A (OSRAM)
NO (1) NO2376485T3 (OSRAM)
NZ (1) NZ593969A (OSRAM)
PL (2) PL2376485T3 (OSRAM)
PT (2) PT3354650T (OSRAM)
RS (1) RS56995B1 (OSRAM)
RU (2) RU2604066C2 (OSRAM)
SG (2) SG10201607592PA (OSRAM)
SI (2) SI3354650T1 (OSRAM)
SM (1) SMT201800181T1 (OSRAM)
TW (3) TWI643854B (OSRAM)
WO (1) WO2010071837A1 (OSRAM)
ZA (1) ZA201104498B (OSRAM)

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KR101712576B1 (ko) 2008-11-10 2017-03-06 버텍스 파마슈티칼스 인코포레이티드 Atr 키나제의 억제제로서 유용한 화합물
PL2376485T3 (pl) 2008-12-19 2018-05-30 Vertex Pharmaceuticals Incorporated Pochodne pirazyny użyteczne jako inhibitory kinazy ATR
US8415381B2 (en) 2009-07-30 2013-04-09 Novartis Ag Heteroaryl compounds and their uses
JP2011057661A (ja) * 2009-08-14 2011-03-24 Bayer Cropscience Ag 殺虫性カルボキサミド類
WO2011143419A1 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Pyrazines useful as inhibitors of atr kinase
MX2012013082A (es) 2010-05-12 2013-05-09 Vertex Pharma Derivados de 2-aminopiridina utiles como iinhibidores de cinasa atr.
EP2569287B1 (en) * 2010-05-12 2014-07-09 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
WO2011143423A2 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CA2798763A1 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
MX2013000103A (es) 2010-06-23 2013-06-13 Vertex Pharma Derivados de pirrolo-pirazina utiles como inhibidores de cinasa art.
US8962623B2 (en) 2011-03-04 2015-02-24 Locus Pharmaceuticals, Inc. Aminopyrazine compounds
CN103476768B (zh) * 2011-03-16 2015-07-08 弗·哈夫曼-拉罗切有限公司 6,5-杂环炔丙醇化合物及其用途
KR20140027974A (ko) 2011-04-05 2014-03-07 버텍스 파마슈티칼스 인코포레이티드 Tra 키나제의 억제제로서 유용한 아미노피라진 화합물
AU2012259333B2 (en) * 2011-05-23 2017-06-08 Merck Patent Gmbh Pyridine-and pyrazine derivatives
EP2723747A1 (en) 2011-06-22 2014-04-30 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
JP2014517079A (ja) 2011-06-22 2014-07-17 バーテックス ファーマシューティカルズ インコーポレイテッド Atrキナーゼ阻害剤として有用な化合物
JP2014520161A (ja) 2011-06-22 2014-08-21 バーテックス ファーマシューティカルズ インコーポレイテッド Atrキナーゼ阻害剤として有用な化合物
EP2755652B1 (en) 2011-09-16 2021-06-02 Novartis AG N-substituted heterocyclyl carboxamides
ES2558457T3 (es) * 2011-09-16 2016-02-04 Novartis Ag Compuestos heterocíclicos para el tratamiento de fibrosis quística
WO2013049719A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
HUE046429T2 (hu) * 2011-09-30 2020-03-30 Vertex Pharma ATR kináz inhibítoraként használható vegyületek elõállítására szolgáló eljárás
JP2014528419A (ja) * 2011-09-30 2014-10-27 バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated Atrキナーゼ阻害剤として有用な化合物
US8853217B2 (en) * 2011-09-30 2014-10-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
MX392542B (es) * 2011-09-30 2025-03-24 Vertex Pharma Tratamiento del cancer de pancreas y del cancer de pulmon de celulas no pequeñas con inhibidores de atr.
WO2013071085A1 (en) * 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
EP2776422A1 (en) 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013071088A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
EP2776420A1 (en) * 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
WO2013071094A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CN108478577A (zh) 2012-04-05 2018-09-04 沃泰克斯药物股份有限公司 可用作atr激酶抑制剂的化合物及其组合疗法
IN2014KN02601A (OSRAM) 2012-04-24 2015-05-08 Vertex Pharma
US8999632B2 (en) 2012-10-04 2015-04-07 Vertex Pharmaceuticals Incorporated Method for measuring ATR inhibition mediated increases in DNA damage
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