KR20230016194A - 취약한 x 관련 장애 치료를 위한 새로운 맥시-k 칼륨 채널 개방제 - Google Patents

취약한 x 관련 장애 치료를 위한 새로운 맥시-k 칼륨 채널 개방제 Download PDF

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KR20230016194A
KR20230016194A KR1020227044772A KR20227044772A KR20230016194A KR 20230016194 A KR20230016194 A KR 20230016194A KR 1020227044772 A KR1020227044772 A KR 1020227044772A KR 20227044772 A KR20227044772 A KR 20227044772A KR 20230016194 A KR20230016194 A KR 20230016194A
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alkylene
alkyl
chloro
trifluoromethyl
methyl
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Korean (ko)
Inventor
로먼 플렉
존 프로우드풋
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카이로스 바이오사이언스 리미티드
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Publication of KR20230016194A publication Critical patent/KR20230016194A/ko
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/30Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32Oxygen atoms
    • C07D209/34Oxygen atoms in position 2
    • 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
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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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    • 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
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • 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
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41781,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42Oxazoles
    • A61K31/424Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
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    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
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    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/30Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D401/10Heterocyclic 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
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • 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
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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 carbon chain containing aromatic rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
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    • 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
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10Spiro-condensed systems
    • C07D491/107Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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    • C07D498/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (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)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
KR1020227044772A 2020-05-20 2021-05-20 취약한 x 관련 장애 치료를 위한 새로운 맥시-k 칼륨 채널 개방제 Pending KR20230016194A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP20175820.8A EP3912625A1 (en) 2020-05-20 2020-05-20 Novel maxi-k potassium channel openers for the treatment of fragile x associated disorders
EP20175820.8 2020-05-20
PCT/EP2021/063463 WO2021234084A1 (en) 2020-05-20 2021-05-20 Maxi-k potassium channel openers for the treatment of fragile x associated disorders

Publications (1)

Publication Number Publication Date
KR20230016194A true KR20230016194A (ko) 2023-02-01

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KR1020227044772A Pending KR20230016194A (ko) 2020-05-20 2021-05-20 취약한 x 관련 장애 치료를 위한 새로운 맥시-k 칼륨 채널 개방제

Country Status (16)

Country Link
US (1) US20240351994A1 (https=)
EP (2) EP3912625A1 (https=)
JP (1) JP2023528292A (https=)
KR (1) KR20230016194A (https=)
CN (1) CN115666554A (https=)
AU (1) AU2021274879A1 (https=)
BR (1) BR112022023318A2 (https=)
CA (1) CA3177423A1 (https=)
DK (1) DK4153170T3 (https=)
FI (1) FI4153170T3 (https=)
IL (1) IL297493A (https=)
MX (1) MX2022014461A (https=)
PH (1) PH12022553155A1 (https=)
PL (1) PL4153170T3 (https=)
PT (1) PT4153170T (https=)
WO (1) WO2021234084A1 (https=)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20250170120A1 (en) * 2022-01-31 2025-05-29 The Board Of Regents Of The University Of Texas System Allosteric sting modulators and methods of use
WO2025233532A1 (en) 2024-05-10 2025-11-13 Les Laboratoires Servier Maxi-k potassium channel openers and therapeutic applications thereof

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5565483A (en) 1995-06-07 1996-10-15 Bristol-Myers Squibb Company 3-substituted oxindole derivatives as potassium channel modulators
JP2000191661A (ja) * 1998-12-25 2000-07-11 Mitsubishi-Tokyo Pharmaceuticals Inc 環状アミド化合物
FR2807038B1 (fr) 2000-04-03 2002-08-16 Sanofi Synthelabo Nouveaux derives d'indolin-2-one, leur preparation et les compositions pharmaceutiques les contenant
MXPA03000032A (es) 2000-06-29 2003-08-19 Neurosearch As Uso de derivados de oxindol 3-sustituidos como moduladores de los canales de potasio kcnq.
US6348486B1 (en) 2000-10-17 2002-02-19 American Home Products Corporation Methods for modulating bladder function
EP1363624A2 (en) 2001-02-20 2003-11-26 Bristol-Myers Squibb Company Fluoro oxindole derivatives as modulators of kcnq potassium channels
FR2827604B1 (fr) * 2001-07-17 2003-09-19 Sanofi Synthelabo Nouveaux derives de 1-phenylsulfonyl-1,3-dihydro-2h-indol-2- one, un procede pour leur preparation et les compositions pharmaceutiques en contenant
GEP20074230B (en) 2002-03-20 2007-11-12 Bristol Myers Squibb Co Phosphate prodrugs of fluorooxindoles
JP4989976B2 (ja) * 2004-02-13 2012-08-01 プレジデント アンド フェロウズ オブ ハーバード カレッジ 翻訳開始阻害剤としての3−3−二置換オキシインドール
US20070299102A1 (en) * 2004-04-08 2007-12-27 Topo Target A/S Diphenyl Ox-Indol-2-One Compounds and Their Use in the Treatment of Cancer
US7576082B2 (en) * 2005-06-24 2009-08-18 Hoffman-La Roche Inc. Oxindole derivatives
JP2010525024A (ja) * 2007-04-24 2010-07-22 トポターゲット・アクティーゼルスカブ 置換3−(4−ヒドロキシフェニル)−インドリン−2−オン化合物
FR2920023B1 (fr) * 2007-08-16 2013-02-08 Sanofi Aventis Derives de l'indol-2-one disubstitues en 3, leur preparation et leur application en therapeutique
US8703775B2 (en) * 2007-12-07 2014-04-22 AbbVie Deutschland GmbH & Co. KG Amidomethyl-substituted oxindole derivatives and the use thereof for the treatment of vasopressin-dependent illnesses
JO3032B1 (ar) * 2008-10-17 2016-09-05 Xenon Pharmaceuticals Inc مركبات سبيرو – اوكسندول وإستعمالاتها كعوامل علاجية.
EP2540295A1 (en) 2011-06-27 2013-01-02 Centre national de la recherche scientifique Compositions for the treatment of Fragile X syndrome
JP6370368B2 (ja) 2013-03-27 2018-08-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Brd4阻害剤としてのインドリノン類似体
US20180318285A1 (en) * 2015-03-10 2018-11-08 President And Fellows Of Harvard College Methods for treatment of autism spectrum disorders
EP3601235B1 (en) * 2017-03-30 2026-03-04 XWPharma Ltd. Bicyclic heteroaryl derivatives, preparation and therapeutic uses thereof
WO2020183307A1 (en) * 2019-03-08 2020-09-17 The University Of Buea Dihydro-spiro[indoline-3:1'-isoquinolin]-2-ones and their analogues and derivatives and methods of treating cancer and other diseases

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Publication number Publication date
JP2023528292A (ja) 2023-07-04
EP3912625A1 (en) 2021-11-24
CN115666554A (zh) 2023-01-31
FI4153170T3 (fi) 2026-03-20
BR112022023318A2 (pt) 2022-12-20
MX2022014461A (es) 2023-01-05
CA3177423A1 (en) 2021-11-25
EP4153170A1 (en) 2023-03-29
PL4153170T3 (pl) 2026-04-20
PT4153170T (pt) 2026-03-13
DK4153170T3 (da) 2026-03-23
EP4153170B1 (en) 2026-01-21
IL297493A (en) 2022-12-01
PH12022553155A1 (en) 2024-02-26
US20240351994A1 (en) 2024-10-24
WO2021234084A1 (en) 2021-11-25
AU2021274879A1 (en) 2022-12-08

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