AU2013366513B2 - Novel benzimidazole derivatives as kinase inhibitors - Google Patents

Novel benzimidazole derivatives as kinase inhibitors Download PDF

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AU2013366513B2
AU2013366513B2 AU2013366513A AU2013366513A AU2013366513B2 AU 2013366513 B2 AU2013366513 B2 AU 2013366513B2 AU 2013366513 A AU2013366513 A AU 2013366513A AU 2013366513 A AU2013366513 A AU 2013366513A AU 2013366513 B2 AU2013366513 B2 AU 2013366513B2
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heterocycle
independently selected
optionally substituted
substituents independently
group
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AU2013366513A1 (en
Inventor
Krzysztof Brzozka
Wieslaw Marek Cholody
Wojciech Czardybon
Michal GALEZOWSKI
Pawel GUZIK
Raymond Horvath
Mariusz Milik
Marta PROKOP
Tomasz RZYMSKI
Aleksandra Sabiniarz
Katarzyna WIKLIK
Ewelina WINCZA
Renata Windak
Magdalena ZAWADZKA
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Ryvu Therapeutics SA
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Ryvu Therapeutics SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
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    • A61P19/00—Drugs for skeletal disorders
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    • A—HUMAN NECESSITIES
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
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    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/14—Radicals substituted by nitrogen atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
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    • C07D401/04—Heterocyclic 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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    • C07D401/12—Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07D401/14—Heterocyclic 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 three or more hetero rings
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
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    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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    • 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
    • C07D487/08—Bridged systems

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  • Chemical & Material Sciences (AREA)
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  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
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AU2013366513A 2012-12-21 2013-12-20 Novel benzimidazole derivatives as kinase inhibitors Active AU2013366513B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1223265.8A GB201223265D0 (en) 2012-12-21 2012-12-21 Novel benzimidazole derivatives as kinase inhibitors
GB1223265.8 2012-12-21
PCT/EP2013/077754 WO2014096388A2 (en) 2012-12-21 2013-12-20 Novel benzimidazole derivatives as kinase inhibitors

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AU2013366513A1 AU2013366513A1 (en) 2015-06-11
AU2013366513B2 true AU2013366513B2 (en) 2016-09-01

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US (2) US9388192B2 (enExample)
EP (1) EP2935244B1 (enExample)
JP (1) JP6169185B2 (enExample)
KR (1) KR101779272B1 (enExample)
CN (1) CN104936951B (enExample)
AU (1) AU2013366513B2 (enExample)
BR (1) BR112015014701B8 (enExample)
CA (1) CA2896156C (enExample)
CY (1) CY1120692T1 (enExample)
DK (1) DK2935244T3 (enExample)
ES (1) ES2688395T3 (enExample)
GB (1) GB201223265D0 (enExample)
HR (1) HRP20181429T8 (enExample)
HU (1) HUE039376T2 (enExample)
IL (1) IL239193A0 (enExample)
LT (1) LT2935244T (enExample)
MX (1) MX369589B (enExample)
PL (1) PL2935244T3 (enExample)
PT (1) PT2935244T (enExample)
RS (1) RS57658B1 (enExample)
SI (1) SI2935244T1 (enExample)
SM (1) SMT201800473T1 (enExample)
WO (1) WO2014096388A2 (enExample)

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GB201223265D0 (en) 2012-12-21 2013-02-06 Selvita Sa Novel benzimidazole derivatives as kinase inhibitors
TN2016000270A1 (en) 2014-01-14 2017-10-06 Millennium Pharm Inc Heteroaryls and uses thereof.
WO2015108881A1 (en) 2014-01-14 2015-07-23 Millennium Pharmaceuticals, Inc. Heteroaryls and uses thereof
TW202140422A (zh) 2014-10-06 2021-11-01 美商維泰克斯製藥公司 囊腫纖維化症跨膜傳導調節蛋白之調節劑
AU2016315881B2 (en) 2015-09-03 2019-09-19 The Arizona Board Of Regents On Behalf Of The University Of Arizona Small molecule inhibitors of DYRK1A and uses thereof
ES2946970T3 (es) 2016-03-31 2023-07-28 Vertex Pharma Regulador de conductancia transmembrana de moduladores de fibrosis quística
GEP20217329B (en) 2016-09-30 2021-12-10 Vertex Pharma Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
EA202192783A1 (ru) 2016-12-09 2022-02-24 Вертекс Фармасьютикалз Инкорпорейтед Модулятор регулятора трансмембранной проводимости при муковисцидозе, фармацевтические композиции, способы лечения и способ получения указанного модулятора
US9855255B1 (en) 2017-05-26 2018-01-02 King Saud University Substituted naphthyridinyl hydrazines as anti-liver cancer agents
MA54105A (fr) 2017-06-08 2021-09-15 Vertex Pharma Méthodes de traitement de la fibrose kystique
IL272032B2 (en) 2017-07-17 2026-04-01 Vertex Pharma Combination therapy for the treatment of cystic fibrosis including N-(1,3-DIMETHYLPYRAZOL-4-YL)SULFONYL-6-[3-(3,3,3-TRIFLUORO-2,2- DIMETHYL-PROPOXY)PYRAZOL-1-YL]-2-[(4S)-2,2,4- TRIMETHYLPYRROLIDIN-1-YL]PYRIDINE-3-CARBOXAMIDE and
MA49752A (fr) 2017-08-02 2021-04-21 Vertex Pharma Procédés de préparation de composés de pyrrolidine
CN111417394B (zh) 2017-10-19 2023-11-07 帝人制药株式会社 苯并咪唑衍生物及其用途
CA3078893A1 (en) 2017-10-19 2019-04-25 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of cftr modulators
KR102716244B1 (ko) 2017-12-08 2024-10-14 버텍스 파마슈티칼스 인코포레이티드 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법
TWI810243B (zh) 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
US12528810B2 (en) 2018-03-01 2026-01-20 Arizona Board Of Regents On Behalf Of The University Of Arizona Small molecule inhibitors of DYRK/CLK and uses thereof
WO2019200246A1 (en) 2018-04-13 2019-10-17 Alexander Russell Abela Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
WO2021096314A1 (ko) * 2019-11-15 2021-05-20 가천대학교 산학협력단 신규한 벤즈이미다졸 유도체 및 이의 용도
CN113491691B (zh) * 2020-04-02 2023-04-14 深圳贝瑞生物医药科技有限公司 一种用于制备抗肿瘤药物或14-3-3η蛋白抑制剂的化合物
KR102854745B1 (ko) * 2020-04-23 2025-09-04 진크래프트 주식회사 R-point 조절 단백질 복합체를 유효성분으로 포함하는 폐암 치료용 약학적 조성물, 상기 복합체의 형성 여부를 이용한 폐암 치료제 스크리닝 방법 및 폐암 진단 방법
WO2023241627A1 (en) * 2022-06-15 2023-12-21 Insilico Medicine Ip Limited Cdk8/19 dual inhibitors and methods of use thereof
CN119836291A (zh) 2022-07-29 2025-04-15 雷沃医疗有限公司 包含bcl-2抑制剂的癌症组合疗法
JP2025523941A (ja) 2022-07-29 2025-07-25 アールワイヴィーユー セラピューティクス エス．エー． Ｆｌｔ３阻害剤を含む癌併用療法
CN120826396A (zh) * 2023-03-06 2025-10-21 英矽智能科技(上海)有限公司 Cdk8/19双重抑制剂及其使用方法
CN120004808B (zh) * 2023-11-15 2025-11-25 宜昌人福药业有限责任公司 一种2-溴-5,6-二氯-1h-苯并咪唑的制备方法
WO2026132392A1 (en) 2024-12-20 2026-06-25 Berlin-Chemie Ag Cancer therapy of subjects carrying mutations in a splicing factor gene

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