MA37929B1 - Composés bis(fluoroalkyl) -1,4-benzodiazépinones en tant qu'inhibiteurs de notch - Google Patents

Composés bis(fluoroalkyl) -1,4-benzodiazépinones en tant qu'inhibiteurs de notch

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Publication number
MA37929B1
MA37929B1 MA37929A MA37929A MA37929B1 MA 37929 B1 MA37929 B1 MA 37929B1 MA 37929 A MA37929 A MA 37929A MA 37929 A MA37929 A MA 37929A MA 37929 B1 MA37929 B1 MA 37929B1
Authority
MA
Morocco
Prior art keywords
compounds
fluoroalkyl
bis
notch inhibitors
benzodiazepinone compounds
Prior art date
Application number
MA37929A
Other languages
English (en)
Other versions
MA37929A1 (fr
Inventor
Ashvinikumar V Gavai
George V Delucca
Daniel O'malley
Patrice Gill
Claude A Quesnelle
Brian E Fink
Yufen Zhao
Francis Y Lee
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of MA37929A1 publication Critical patent/MA37929A1/fr
Publication of MA37929B1 publication Critical patent/MA37929B1/fr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/555Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/66Phosphorus compounds
    • A61K31/675Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D243/00Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/141,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/161,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/181,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
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    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/141,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/161,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/181,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24Oxygen atoms
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    • C07D243/10Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/141,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/161,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/181,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24Oxygen atoms
    • C07D243/26Preparation from compounds already containing the benzodiazepine skeleton
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    • 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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    • C07F7/02Silicon compounds
    • C07F7/08Compounds having one or more C—Si linkages
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    • C07F9/02Phosphorus compounds
    • C07F9/06Phosphorus compounds without P—C bonds
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    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/38Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
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    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
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    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4866Organic macromolecular compounds

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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  • Gastroenterology & Hepatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Abstract

L'invention concerne des composés de formule (i) et/ou des sels de ceux-ci : formule (i) dans laquelle r1 représente ch2ch2cf3; r2 représente ch2ch2cf3ou ch2ch2ch2cf3; r3 représente h, ch3, ou rx; r4 représente h ou ry; le cycle a représente phényle ou pyridinyle ; et rx, ry, ra, rb, y et z sont tels que définis dans la description. L'invention concerne également des méthodes d'utilisation desdits composés pour inhiber le récepteur notch, et des compositions pharmaceutiques comprenant ces composés. Ces composés sont utiles dans le traitement, la prévention ou le ralentissement de la progression de maladies ou de troubles dans divers domaines thérapeutiques, comme le cancer ; ou en tant que promédicaments desdits composés.
MA37929A 2012-09-21 2013-09-20 Composés bis(fluoroalkyl) -1,4-benzodiazépinones en tant qu'inhibiteurs de notch MA37929B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261703912P 2012-09-21 2012-09-21
PCT/US2013/060790 WO2014047372A1 (fr) 2012-09-21 2013-09-20 Composés bis(fluoroalkyl) -1,4-benzodiazépinones en tant qu'inhibiteurs de notch

Publications (2)

Publication Number Publication Date
MA37929A1 MA37929A1 (fr) 2018-06-29
MA37929B1 true MA37929B1 (fr) 2018-09-28

Family

ID=49263506

Family Applications (1)

Application Number Title Priority Date Filing Date
MA37929A MA37929B1 (fr) 2012-09-21 2013-09-20 Composés bis(fluoroalkyl) -1,4-benzodiazépinones en tant qu'inhibiteurs de notch

Country Status (34)

Country Link
US (2) US8999918B2 (fr)
EP (1) EP2897945B1 (fr)
JP (1) JP6165255B2 (fr)
KR (1) KR102155588B1 (fr)
CN (1) CN104703976B (fr)
AR (1) AR093767A1 (fr)
AU (1) AU2013317923B2 (fr)
BR (1) BR112015005817B1 (fr)
CA (1) CA2885574C (fr)
CL (1) CL2015000711A1 (fr)
CO (1) CO7310522A2 (fr)
CY (1) CY1118739T1 (fr)
DK (1) DK2897945T3 (fr)
EA (1) EA027281B1 (fr)
ES (1) ES2617591T3 (fr)
HR (1) HRP20170352T8 (fr)
HU (1) HUE032038T2 (fr)
IL (1) IL237782A (fr)
LT (1) LT2897945T (fr)
MA (1) MA37929B1 (fr)
MX (1) MX367474B (fr)
MY (1) MY185233A (fr)
NZ (1) NZ707171A (fr)
PE (1) PE20150622A1 (fr)
PH (1) PH12015500414A1 (fr)
PL (1) PL2897945T3 (fr)
PT (1) PT2897945T (fr)
RS (1) RS55779B1 (fr)
SG (1) SG11201501573UA (fr)
SI (1) SI2897945T1 (fr)
TN (1) TN2015000102A1 (fr)
TW (1) TWI614238B (fr)
UY (1) UY35041A (fr)
WO (1) WO2014047372A1 (fr)

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JP2015531792A (ja) 2012-09-21 2015-11-05 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 1,4−ベンゾジアゼピノン化合物のプロドラッグ
WO2014047397A1 (fr) 2012-09-21 2014-03-27 Bristol-Myers Squibb Company Composés de fluoralkyl- et de fluorocycloalkyl-1,4-benzodiazépinone utilisables en tant qu'inhibiteurs du récepteur notch
WO2014047370A1 (fr) 2012-09-21 2014-03-27 Bristol-Myers Squibb Company Composés fluoroalkyl benzodiazépinones
UA110688C2 (uk) 2012-09-21 2016-01-25 Пфайзер Інк. Біциклічні піридинони
JP2015534554A (ja) 2012-09-21 2015-12-03 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company アルキル,フルオロアルキル−1,4−ベンゾジアゼピノン化合物
EP2897960B1 (fr) 2012-09-21 2016-08-03 Bristol-Myers Squibb Company Composés hétérocycliques tricycliques utilisables en tant qu'inhibiteurs du récepteur notch
US9187434B2 (en) 2012-09-21 2015-11-17 Bristol-Myers Squibb Company Substituted 1,5-benzodiazepinones compounds
US9133139B2 (en) 2012-09-21 2015-09-15 Bristol-Myers Squibb Company Fluoroalkyl-1,4-benzodiazepinone compounds
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EA033423B1 (ru) 2015-02-03 2019-10-31 Pfizer Циклопропанбензофуранилпиридопиразиндионы
EP3790553A4 (fr) * 2018-05-06 2022-04-20 Ayala Pharmaceuticals Inc. Compositions comprenant des inhibiteurs de cd20 et des composés de bisfluoroalkyl-1,4-benzodiazépinone et leurs procédés d'utilisation
SG11202011041YA (en) * 2018-05-06 2020-12-30 Ayala Pharmaceuticals Inc Combination compositions comprising bisfluoroalkyl-1,4- benzodiazepinone compounds and methods of use thereof
JP2021523190A (ja) * 2018-05-15 2021-09-02 アヤラ ファーマシューティカルズ インコーポレイテッド 腺様嚢胞癌を治療するためのビスフルオロアルキル−1,4−ベンゾジアゼピノン化合物を含む組成物
CA3100202A1 (fr) * 2018-05-15 2019-11-21 Bristol-Myers Squibb Company Compositions comprenant des composes de bisfluoroalkyl-1,4-benzodiazepinone et methodes d'utilisation associees
WO2019226329A1 (fr) * 2018-05-24 2019-11-28 Ayala Pharmaceuticals Inc. Compositions comprenant des composés bisfluoroalkyl-1,4-benzodiazépinone et des agents immunothérapeutiques et leurs méthodes d'utilisation
US20220192984A1 (en) 2018-10-02 2022-06-23 Frequency Therapeutics, Inc. Pharmaceutical compositions comprising otic therapeutic agents and related methods
SG11202111191YA (en) 2019-04-08 2021-11-29 Frequency Therapeutics Inc Combination of chir99021 and valproic acid for treating hearing loss
US20230108536A1 (en) * 2020-02-16 2023-04-06 Ayala Pharmaceuticals Inc. Methods of preparing chiral benzodiazepinone derivatives
WO2022051442A1 (fr) 2020-09-03 2022-03-10 Bristol-Myers Squibb Company Polymorphes de composés de bis(fluoroalkyl)-1,4-benzodiazépinone et leurs utilisations
CN112142629B (zh) * 2020-10-10 2021-09-14 西北工业大学 3-氨基磺酰基丙氨酸的制备方法
EP4008324A1 (fr) 2020-12-07 2022-06-08 Cellestia Biotech AG Combinaisons comprenant un inhibiteur d'une protéine anti-apoptotique, telle que bcl-2, bcl-xl, bclw ou mcl-1, et un inhibiteur de voie de signalisation notch pour le traitement du cancer
WO2022122667A1 (fr) 2020-12-07 2022-06-16 Cellestia Biotech Ag Combinaisons pharmaceutiques pour le traitement du cancer
CN117794536A (zh) 2021-06-02 2024-03-29 塞莱斯蒂亚生物技术股份公司 在治疗自身免疫性和炎症性疾病的方法中使用的化合物
WO2023079132A1 (fr) 2021-11-08 2023-05-11 Cellestia Biotech Ag Combinaisons pharmaceutiques pour le traitement du cancer
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