CA2856347C - Fused tricyclic compounds as raf kinase inhibitors - Google Patents

Fused tricyclic compounds as raf kinase inhibitors Download PDF

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Publication number
CA2856347C
CA2856347C CA2856347A CA2856347A CA2856347C CA 2856347 C CA2856347 C CA 2856347C CA 2856347 A CA2856347 A CA 2856347A CA 2856347 A CA2856347 A CA 2856347A CA 2856347 C CA2856347 C CA 2856347C
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Prior art keywords
heterocyclyl
compound
heteroaryl
alkyl
cycloalkyl
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CA2856347A
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English (en)
French (fr)
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CA2856347A1 (en
Inventor
Changyou Zhou
Shaohui Wang
Guoliang Zhang
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BeOne Medicines Ltd
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Beigene Ltd
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    • 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
    • A61K31/5365—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 ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/28—Oxygen atom
    • C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C07D519/02—Ergot alkaloids of the cyclic peptide type

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
CA2856347A 2011-12-31 2011-12-31 Fused tricyclic compounds as raf kinase inhibitors Active CA2856347C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2011/085146 WO2013097224A1 (en) 2011-12-31 2011-12-31 Fused tricyclic compounds as raf kinase inhibitors

Publications (2)

Publication Number Publication Date
CA2856347A1 CA2856347A1 (en) 2013-07-04
CA2856347C true CA2856347C (en) 2017-05-30

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Family Applications (1)

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CA2856347A Active CA2856347C (en) 2011-12-31 2011-12-31 Fused tricyclic compounds as raf kinase inhibitors

Country Status (28)

Country Link
US (3) US9273046B2 (enEXAMPLES)
EP (2) EP3124472B1 (enEXAMPLES)
JP (1) JP5868521B2 (enEXAMPLES)
KR (1) KR101713391B1 (enEXAMPLES)
CN (1) CN103596926B (enEXAMPLES)
AU (1) AU2011384857B2 (enEXAMPLES)
BR (1) BR112014013108B1 (enEXAMPLES)
CA (1) CA2856347C (enEXAMPLES)
CY (1) CY1118226T1 (enEXAMPLES)
DK (1) DK2797888T3 (enEXAMPLES)
EA (1) EA025597B1 (enEXAMPLES)
ES (1) ES2588775T3 (enEXAMPLES)
HR (1) HRP20160641T1 (enEXAMPLES)
HU (1) HUE029656T2 (enEXAMPLES)
IL (1) IL233364A (enEXAMPLES)
IN (1) IN2014DN06166A (enEXAMPLES)
LT (1) LT2797888T (enEXAMPLES)
ME (1) ME02529B (enEXAMPLES)
MX (1) MX352617B (enEXAMPLES)
NZ (1) NZ624068A (enEXAMPLES)
PL (1) PL2797888T3 (enEXAMPLES)
PT (1) PT2797888T (enEXAMPLES)
RS (1) RS55196B1 (enEXAMPLES)
SG (1) SG11201401725SA (enEXAMPLES)
SI (1) SI2797888T1 (enEXAMPLES)
SM (1) SMT201600302B (enEXAMPLES)
WO (1) WO2013097224A1 (enEXAMPLES)
ZA (1) ZA201405555B (enEXAMPLES)

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NZ716392A (en) 2013-06-28 2017-03-31 Beigene Ltd Fused tricyclic urea compounds as raf kinase and/or raf kinase dimer inhibitors
US9670231B2 (en) 2013-06-28 2017-06-06 Beigene, Ltd. Fused tricyclic amide compounds as multiple kinase inhibitors
WO2015089809A1 (en) * 2013-12-19 2015-06-25 Merck Sharp & Dohme Corp. Antidiabetic substituted heteroaryl compounds
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JP6993056B2 (ja) * 2016-07-05 2022-02-15 ベイジーン リミテッド 癌治療のためのｐｄ－１アンタゴニスト及びｒａｆ阻害剤の組合せ
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KR20230058399A (ko) 2020-07-28 2023-05-03 재즈 파마슈티칼즈 아일랜드 리미티드 융합된 바이사이클릭 raf 억제제 및 이의 사용 방법
JP2023539663A (ja) 2020-08-28 2023-09-15 アルビナス・オペレーションズ・インコーポレイテッド 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法
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AU2021412688B2 (en) * 2020-12-29 2025-06-12 Txinno Bioscience Inc. Novel naphthyridinone derivative having inhibitory activity against ectonucleotide pyrophosphatase-phosphodiesterase and use thereof
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NZ624068A (en) 2011-12-31 2016-09-30 Beigene Ltd Fused tricyclic compounds as raf kinase inhibitors
CN113307805A (zh) 2015-04-15 2021-08-27 百济神州有限公司 B-raf激酶抑制剂的马来酸盐、其结晶形式、制备方法和用途

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IN2014DN06166A (enEXAMPLES) 2015-08-21
WO2013097224A1 (en) 2013-07-04
LT2797888T (lt) 2016-10-10
EP2797888A4 (en) 2015-09-02
ME02529B (me) 2017-02-20
US9273046B2 (en) 2016-03-01
US20190000857A1 (en) 2019-01-03
ZA201405555B (en) 2015-10-28
AU2011384857B2 (en) 2016-03-03
US20160206621A1 (en) 2016-07-21
CN103596926B (zh) 2015-11-25
HRP20160641T1 (hr) 2016-09-23
US20150045355A1 (en) 2015-02-12
NZ624068A (en) 2016-09-30
AU2011384857A1 (en) 2014-05-29
IL233364A0 (en) 2014-08-31
HUE029656T2 (en) 2017-03-28
JP5868521B2 (ja) 2016-02-24
US10576087B2 (en) 2020-03-03
BR112014013108A2 (pt) 2017-06-13
CA2856347A1 (en) 2013-07-04
JP2015506353A (ja) 2015-03-02
ES2588775T3 (es) 2016-11-04
BR112014013108B1 (pt) 2020-11-24
PT2797888T (pt) 2016-09-09
EP3124472B1 (en) 2018-07-25
PL2797888T3 (pl) 2016-12-30
RS55196B1 (sr) 2017-01-31
SG11201401725SA (en) 2014-09-26
MX352617B (es) 2017-12-01
EA201491305A1 (ru) 2015-04-30
EP3124472A1 (en) 2017-02-01
HK1192232A1 (zh) 2014-08-15
MX2014007829A (es) 2014-08-01
EP2797888B1 (en) 2016-06-08
EA025597B1 (ru) 2017-01-30
DK2797888T3 (en) 2016-09-19
EP2797888A1 (en) 2014-11-05
US9895376B2 (en) 2018-02-20
HK1221222A1 (zh) 2017-05-26
CY1118226T1 (el) 2017-06-28
IL233364A (en) 2017-06-29
SMT201600302B (it) 2016-11-10
SI2797888T1 (sl) 2017-01-31
CN103596926A (zh) 2014-02-19
KR101713391B1 (ko) 2017-03-07
KR20140108541A (ko) 2014-09-11

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