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)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (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)

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US (3) US9273046B2 (oth)
EP (2) EP2797888B1 (oth)
JP (1) JP5868521B2 (oth)
KR (1) KR101713391B1 (oth)
CN (1) CN103596926B (oth)
AU (1) AU2011384857B2 (oth)
BR (1) BR112014013108B1 (oth)
CA (1) CA2856347C (oth)
CY (1) CY1118226T1 (oth)
DK (1) DK2797888T3 (oth)
EA (1) EA025597B1 (oth)
ES (1) ES2588775T3 (oth)
HR (1) HRP20160641T1 (oth)
HU (1) HUE029656T2 (oth)
IL (1) IL233364A (oth)
IN (1) IN2014DN06166A (oth)
LT (1) LT2797888T (oth)
ME (1) ME02529B (oth)
MX (1) MX352617B (oth)
NZ (1) NZ624068A (oth)
PL (1) PL2797888T3 (oth)
PT (1) PT2797888T (oth)
RS (1) RS55196B1 (oth)
SG (1) SG11201401725SA (oth)
SI (1) SI2797888T1 (oth)
SM (1) SMT201600302B (oth)
WO (1) WO2013097224A1 (oth)
ZA (1) ZA201405555B (oth)

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US9670203B2 (en) * 2013-06-28 2017-06-06 Beigene, Ltd. Fused tricyclic urea compounds as Raf kinase and/or Raf kinase dimer inhibitors
WO2015089809A1 (en) * 2013-12-19 2015-06-25 Merck Sharp & Dohme Corp. Antidiabetic substituted heteroaryl compounds
WO2015176267A1 (en) * 2014-05-22 2015-11-26 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
GB201416186D0 (en) * 2014-09-12 2014-10-29 Redx Pharma Ltd Compounds
NZ735715A (en) * 2015-04-15 2022-09-30 Beigene Ltd Maleate salts of a b-raf kinase inhibitor, crystalline forms, methods of preparation, and uses therefore
JP6175519B2 (ja) * 2016-01-04 2017-08-09 ベイジーン リミテッド Ｒａｆキナーゼ阻害剤としての縮合三環式化合物
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JP2023535790A (ja) 2020-07-28 2023-08-21 ジャズ ファーマシューティカルズ アイルランド リミテッド 縮合二環式ｒａｆ阻害薬及びその使用方法
JP7834721B2 (ja) 2020-08-28 2026-03-24 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
AR123492A1 (es) 2020-09-14 2022-12-07 Arvinas Operations Inc Formas cristalinas y amorfas de un compuesto para la degradación dirigida del receptor de estrógeno
WO2022146022A1 (ko) * 2020-12-29 2022-07-07 주식회사 티씨노바이오사이언스 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 나프티리딘온 유도체 및 이들의 용도
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NZ735715A (en) 2015-04-15 2022-09-30 Beigene Ltd Maleate salts of a b-raf kinase inhibitor, crystalline forms, methods of preparation, and uses therefore

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

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