[go: up one dir, main page]

PE20150622A1 - Compuestos de bis(fluoroalquil)-1,4-benzodiazepinona como inhibidores de notch - Google Patents

Compuestos de bis(fluoroalquil)-1,4-benzodiazepinona como inhibidores de notch

Info

Publication number
PE20150622A1
PE20150622A1 PE2015000392A PE2015000392A PE20150622A1 PE 20150622 A1 PE20150622 A1 PE 20150622A1 PE 2015000392 A PE2015000392 A PE 2015000392A PE 2015000392 A PE2015000392 A PE 2015000392A PE 20150622 A1 PE20150622 A1 PE 20150622A1
Authority
PE
Peru
Prior art keywords
cyclopropyl
compounds
fluoroalkyl
bis
notch inhibitors
Prior art date
Application number
PE2015000392A
Other languages
English (en)
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49263506&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PE20150622(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of PE20150622A1 publication Critical patent/PE20150622A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic 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
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/02—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
    • 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
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic 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
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds 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
    • A61K31/573—Compounds 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
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic 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
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic 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
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms
    • C07D243/26—Preparation from compounds already containing the benzodiazepine skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/62—Medicinal 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
    • A61K47/64—Drug-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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Dermatology (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)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

LA INVENCION SE REFIERE A COMPUESTOS DE FORMULA (I) Y SALES DEL MISMO, EN DONDE R1 ES -(CH2)2CF3; R2 ES -(CH2)2CF3 O -(CH2)3CF3; R3 ES H, -CH3, -CH2OC(O)CH(CH3)NH2, ENTRE OTROS; R4 ES H, -SCH2CH(NH2)C(O)OH, -SCH2CH(NH2)C(O)OCH3 O -SCH2CH(NH2)C(O)OC(CH3)3; EL ANILLO A ES FENILO O PIRIDINILO; CADA Ra ES INDEPENDIENTEMENTE Cl, ALQUILO C1-3, -CH2OH, -CF3, CICLOPROPILO, -OCH3 U -O(CICLOPROPILO); CADA Rb ES INDEPENDIENTEMENTE F, Cl, -CH3, -CH2OH, -CF3, CICLOPROPILO U -OCH3; y ES 0, 1 o 2; z ES 0, 1 o 2; SIEMPRE QUE SI EL ANILLO A ES FENILO Y z ES 0, ENTONCES y ES 1 o 2 Y AL MENOS UN Ra ES ALQUILO C1-3, -CH2OH, -CF3, CICLOPROPILO U -O(CICLOPROPILO); ENTRE OTROS. LOS COMPUESTOS DE FORMULA (I) SON INHIBIDORES DE NOTCH, POR LO CUAL SON UTILES PARA EL TRATAMIENTO DE AFECCIONES TALES COMO EL CANCER Y OTRAS ENFERMEDADES PROLIFERATIVAS. TAMBIEN SE REFIERE A COMPOSICIONES QUE COMPRENDEN COMPUESTOS DE FORMULA (I).
PE2015000392A 2012-09-21 2013-09-20 Compuestos de bis(fluoroalquil)-1,4-benzodiazepinona como inhibidores de notch PE20150622A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201261703912P 2012-09-21 2012-09-21

Publications (1)

Publication Number Publication Date
PE20150622A1 true PE20150622A1 (es) 2015-05-11

Family

ID=49263506

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2015000392A PE20150622A1 (es) 2012-09-21 2013-09-20 Compuestos de bis(fluoroalquil)-1,4-benzodiazepinona como inhibidores de notch

Country Status (35)

Country Link
US (2) US8999918B2 (es)
EP (1) EP2897945B1 (es)
JP (1) JP6165255B2 (es)
KR (1) KR102155588B1 (es)
CN (1) CN104703976B (es)
AR (1) AR093767A1 (es)
AU (1) AU2013317923B2 (es)
BR (1) BR112015005817B1 (es)
CA (1) CA2885574C (es)
CL (1) CL2015000711A1 (es)
CO (1) CO7310522A2 (es)
CY (1) CY1118739T1 (es)
DK (1) DK2897945T3 (es)
EA (1) EA027281B1 (es)
ES (1) ES2617591T3 (es)
HR (1) HRP20170352T8 (es)
HU (1) HUE032038T2 (es)
IL (1) IL237782A (es)
LT (1) LT2897945T (es)
MA (1) MA37929B1 (es)
MX (1) MX367474B (es)
MY (1) MY185233A (es)
NZ (1) NZ707171A (es)
PE (1) PE20150622A1 (es)
PH (1) PH12015500414B1 (es)
PL (1) PL2897945T3 (es)
PT (1) PT2897945T (es)
RS (1) RS55779B1 (es)
SG (1) SG11201501573UA (es)
SI (1) SI2897945T1 (es)
SM (1) SMT201700153T1 (es)
TN (1) TN2015000102A1 (es)
TW (1) TWI614238B (es)
UY (1) UY35041A (es)
WO (1) WO2014047372A1 (es)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2897944B1 (en) 2012-09-21 2016-10-26 Bristol-Myers Squibb Company Substituted 1,5-benzodiazepinone compounds
JP2015529252A (ja) 2012-09-21 2015-10-05 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ フルオロアルキル−１，４−ベンゾジアゼピノン化合物
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
EP2897941B1 (en) 2012-09-21 2016-09-07 Bristol-Myers Squibb Company Prodrugs of 1,4-benzodiazepinone compounds
EP2897946B1 (en) * 2012-09-21 2016-11-16 Bristol-Myers Squibb Company N-substituted bis(fluoroalkkyl)-1,4-benzodiazepinone compounds as notch inhibitors
UA110688C2 (uk) 2012-09-21 2016-01-25 Пфайзер Інк. Біциклічні піридинони
EP2897960B1 (en) 2012-09-21 2016-08-03 Bristol-Myers Squibb Company Tricyclic heterocyclic compounds as notch inhibitors
WO2014047370A1 (en) 2012-09-21 2014-03-27 Bristol-Myers Squibb Company Fluoroalkyl dibenzodiazepinone compounds
EP2897942B1 (en) 2012-09-21 2016-08-31 Bristol-Myers Squibb Company Fluoroalkyl and fluorocycloalkyl 1,4-benzodiazepinone compounds as notch inhibitors
CN105101968A (zh) 2013-04-04 2015-11-25 百时美施贵宝公司 治疗增殖性疾病的组合疗法
BR112017015693A2 (pt) 2015-02-03 2018-03-20 Pfizer ciclopropabenzofuranil piridopirazinadionas
US20220339162A1 (en) * 2018-05-06 2022-10-27 Ayala Pharmaceuticals Inc. Bisfluoroalkyl-1,4-benzodiazepinone compounds for treating desmoid tumors
WO2019215585A1 (en) * 2018-05-06 2019-11-14 Ayala Pharmaceuticals Inc. Compositions comprising cd20 inhibitors and bisfluoroalkyl-1,4-benzodiazepinone compounds and methods of use thereof
WO2019217250A1 (en) 2018-05-06 2019-11-14 Ayala Pharmaceuticals Inc. Combination compositions comprising bisfluoroalkyl-1,4- benzodiazepinone compounds and methods of use thereof
BR112020023204A2 (pt) * 2018-05-15 2021-02-23 Bristol-Myers Squibb Company composições que compreendem compostos de bisfluoroalquil-1,4-benzodiazepinona e métodos de uso dos mesmos
SG11202011327UA (en) * 2018-05-15 2020-12-30 Ayala Pharmaceuticals Inc Compositions comprising bisfluoroalkyl-l,4-benzodiazepinone compounds for treating adenoid cystic carcinoma
BR112020023975A2 (pt) * 2018-05-24 2021-02-23 Ayala Pharmaceuticals Inc. composições que compreendem os compostos de bisfluoroalquil-1,4-benzodiazepinona e imunoterapêuticos e métodos de uso das mesmas
BR112021006092A2 (pt) 2018-10-02 2021-07-20 Frequency Therapeutics, Inc. composições farmacêuticas que compreendem agentes terapêuticos óticos e métodos relacionados
KR20220007050A (ko) 2019-04-08 2022-01-18 프리퀀시 테라퓨틱스, 인크. 난청을 치료하기 위한 chir99021과 발프로산의 조합
EP4107148A4 (en) 2020-02-16 2024-05-15 Ayala Pharmaceuticals Inc. PROCESS FOR PREPARING CHIRAL BENZODIAZEPINONE DERIVATIVES
IL301060A (en) 2020-09-03 2023-05-01 Bristol Myers Squibb Co Polymorphs of bis(fluoroalkyl)-1,4-benzodiazepine compounds and their uses
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
WO2022122667A1 (en) 2020-12-07 2022-06-16 Cellestia Biotech Ag Pharmaceutical combinations for treating cancer
EP4008324A1 (en) 2020-12-07 2022-06-08 Cellestia Biotech AG Combinations comprising an inhibitor of an anti-apoptotic protein, such as bcl-2, bcl-xl, bclw or mcl-1, and a notch signaling pathway inhibitor for treating cancer
EP4346816A2 (en) 2021-06-02 2024-04-10 Cellestia Biotech AG Compounds for use in a method for treating an autoimmune and inflammatory disease
US20250000870A1 (en) 2021-11-08 2025-01-02 Cellestia Biotech Ag Pharmaceutical Combinations for Treating Cancer
EP4223292A1 (en) 2022-02-07 2023-08-09 Cellestia Biotech AG Pharmaceutical combinations for treating cancer
WO2024036097A1 (en) 2022-08-12 2024-02-15 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds and isotopologues thereof
WO2024145306A1 (en) * 2022-12-28 2024-07-04 Ayala Pharmaceuticals Inc. Intermediate salt for the preparation of bis(fluoroalkyl) benzodiazepinone compounds
AU2024265078A1 (en) 2023-05-04 2025-12-11 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025072117A1 (en) 2023-09-25 2025-04-03 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds and isotopologues thereof
US20250154171A1 (en) 2023-10-12 2025-05-15 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5324726A (en) 1989-12-18 1994-06-28 Merck & Co., Inc. Benzodiazepine analogs
AU2555997A (en) 1996-04-03 1997-10-22 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5852010A (en) 1996-04-03 1998-12-22 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US6635632B1 (en) 1996-12-23 2003-10-21 Athena Neurosciences, Inc. Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds
NZ509241A (en) * 1998-08-07 2003-08-29 Du Pont Pharm Co Succinoylamino lactams as inhibitors of alpha-beta protein production
HRP990246A2 (en) * 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
DE69926254D1 (de) 1998-11-12 2005-08-25 Bristol Myers Squibb Pharma Co Verwendung von radioliganden zum screening von inhibitoren der herstellung von beta-amyloid peptiden
US6737038B1 (en) * 1998-11-12 2004-05-18 Bristol-Myers Squibb Company Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
CA2347671A1 (en) 1998-12-24 2000-07-06 Dupont Pharmaceuticals Company Succinoylamino benzodiazepines as inhibitors of a.beta. protein production
MXPA01011052A (es) 1999-04-30 2002-11-22 Univ Michigan Aplicaciones terapeuticas de benzodiazepinas pro-apoctoticas.
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
AU7997700A (en) 1999-10-08 2001-04-23 Du Pont Pharmaceuticals Company Amino lactam sulfonamides as inhibitors of abeta protein production
JP2003520266A (ja) 2000-01-24 2003-07-02 メルク シャープ エンド ドーム リミテッド γ−セクレターゼ阻害薬
JP2003523345A (ja) * 2000-02-17 2003-08-05 ブリストル−マイヤーズ スクイブ ファーマ カンパニー Ａβタンパク質産生の阻害剤としてのスクシノイルアミノ炭素環および複素環
US6495540B2 (en) 2000-03-28 2002-12-17 Bristol - Myers Squibb Pharma Company Lactams as inhibitors of A-β protein production
WO2001074796A1 (en) 2000-03-31 2001-10-11 Bristol-Myers Squibb Pharma Company SUCCINOYLAMINO HETEROCYCLES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
CA2404023A1 (en) 2000-04-03 2001-10-11 Richard E. Olson Cyclic lactams as inhibitors of a.beta. protein production
US6713476B2 (en) 2000-04-03 2004-03-30 Dupont Pharmaceuticals Company Substituted cycloalkyls as inhibitors of a beta protein production
GB0008710D0 (en) 2000-04-07 2000-05-31 Merck Sharp & Dohme Therapeutic compounds
JP2004500419A (ja) 2000-04-11 2004-01-08 デュポン　ファーマシューティカルズ　カンパニー Ａβタンパク質産生阻害剤としての置換ラクタム
AU2001261728A1 (en) 2000-05-17 2001-11-26 Bristol-Myers Squibb Pharma Company Use of small molecule radioligands for diagnostic imaging
GB0012671D0 (en) 2000-05-24 2000-07-19 Merck Sharp & Dohme Therapeutic agents
HK1049333A1 (zh) 2000-06-01 2003-05-09 Bristol-Myers Squibb Pharma Company 以环状琥珀酸酯代替内酰胺，作为制造Aβ蛋白质的抑制剂
US7001901B2 (en) 2002-08-27 2006-02-21 Bristol-Myers Squibb Company Tetrazolylpropionamides as inhibitors of Aβ protein production
NZ538870A (en) 2002-09-20 2007-04-27 Arrow Therapeutics Ltd Benzodiazepine derivatives and pharmaceutical compositions containing them
MXPA05008172A (es) 2003-02-04 2005-10-05 Hoffmann La Roche Derivados de malonamida como inhibidores gamma-secretasa.
GB0312365D0 (en) 2003-05-30 2003-07-02 Univ Aston Novel 3-substituted-1, 4-benzodiazepines
BRPI0413533A (pt) 2003-09-09 2006-10-10 Hoffmann La Roche derivados de malonamida que bloqueiam a atividade de gama-secretase
EP1795198A1 (en) 2005-12-09 2007-06-13 Hubrecht Laboratorium Treatment of Barret's esophagus
AU2008287124B2 (en) 2007-08-14 2013-06-06 Eli Lilly And Company Azepine derivatives as gamma-secretase inhibitors
BRPI0906831A2 (pt) 2008-01-11 2019-09-24 Hoffmann La Roche uso de um inibidor de gama-secretase para tratamento de câncer
TWI530489B (zh) * 2011-03-22 2016-04-21 必治妥美雅史谷比公司 雙（氟烷基）－１，４－苯二氮呯酮化合物
EP2897946B1 (en) * 2012-09-21 2016-11-16 Bristol-Myers Squibb Company N-substituted bis(fluoroalkkyl)-1,4-benzodiazepinone compounds as notch inhibitors

Also Published As

Publication number Publication date
EA201590581A1 (ru) 2015-07-30
UY35041A (es) 2014-03-31
DK2897945T3 (en) 2017-03-27
MX2015003033A (es) 2015-06-10
MX367474B (es) 2019-08-23
CO7310522A2 (es) 2015-06-30
MY185233A (en) 2021-04-30
EA027281B1 (ru) 2017-07-31
ES2617591T3 (es) 2017-06-19
AU2013317923B2 (en) 2017-06-29
EP2897945A1 (en) 2015-07-29
HRP20170352T1 (hr) 2017-05-05
US9273014B2 (en) 2016-03-01
JP6165255B2 (ja) 2017-07-19
PT2897945T (pt) 2017-03-07
TW201418230A (zh) 2014-05-16
PL2897945T3 (pl) 2017-06-30
BR112015005817B1 (pt) 2022-10-04
SI2897945T1 (sl) 2017-03-31
CN104703976A (zh) 2015-06-10
BR112015005817A2 (pt) 2017-07-04
AU2013317923A1 (en) 2015-05-07
HRP20170352T8 (hr) 2017-05-19
KR102155588B1 (ko) 2020-09-14
CN104703976B (zh) 2017-03-08
AR093767A1 (es) 2015-06-24
NZ707171A (en) 2018-01-26
PH12015500414A1 (en) 2015-04-20
JP2015530411A (ja) 2015-10-15
MA37929B1 (fr) 2018-09-28
US20140087992A1 (en) 2014-03-27
WO2014047372A1 (en) 2014-03-27
SG11201501573UA (en) 2015-05-28
KR20150056780A (ko) 2015-05-27
CA2885574C (en) 2021-06-08
US8999918B2 (en) 2015-04-07
HUE032038T2 (en) 2017-09-28
RS55779B1 (sr) 2017-07-31
CA2885574A1 (en) 2014-03-27
TN2015000102A1 (en) 2016-06-29
US20150166489A1 (en) 2015-06-18
CY1118739T1 (el) 2017-07-12
PH12015500414B1 (en) 2015-04-20
TWI614238B (zh) 2018-02-11
CL2015000711A1 (es) 2015-09-04
MA37929A1 (fr) 2018-06-29
SMT201700153T1 (it) 2017-05-08
EP2897945B1 (en) 2016-12-21
LT2897945T (lt) 2017-03-27
IL237782A (en) 2017-03-30

Similar Documents

Publication Publication Date Title
PE20150622A1 (es) Compuestos de bis(fluoroalquil)-1,4-benzodiazepinona como inhibidores de notch
CL2013002690A1 (es) Compuestos derivados de bis(fluoroalquil)-1,4-benzodiazepinona, inhibidores de notch; compuesto cristalino; composicion farmaceutica que los comprende; combinacion farmaceutica; y su uso para el tratamiento del cancer.
CU20180144A7 (es) Derivados de carbonucleósidos sustituidos útiles como agentes antineoplásicos
SV2017005514A (es) Derivados de nucleósidos sustituidos útiles como agentes antineoplásicos
CU20160167A7 (es) Compuestos de pirazolopiridinas y pirazolopirimidinas útiles en el tratamiento de condiciones alérgicas y respiratorias
CU20170164A7 (es) Compuestos n-tieno (2,3-d)pirimidinil-d-fenilalanina, método para preparar los mismos y composiciones farmacéuticas que los contienen
MX2016013689A (es) Compuestos 4-amino-imidazoquinolina.
PE20181298A1 (es) Inhibidores de bromodominio bivalentes y usos de los mismos
CO7400867A2 (es) Modificador del sabor dulce
UY35898A (es) ?compuestos inhibidores de syk y composiciones que los comprenden?.
PE20151001A1 (es) Alcoxipirazoles como activadores de guanilato ciclasa soluble
EA201401189A1 (ru) Замещенные n-(тетразол-5-ил)- и n-(триазол-5-ил)арилкарбоксамидные соединения и их применение в качестве гербицидов
PE20150776A1 (es) 6-aminoacido-heteroarildihidropirimidinas para el tratamiento y profilaxis de la infeccion del virus de la hepatitis b
PE20171338A1 (es) Compuestos y composiciones como inhibidores de quinasa raf
MX381235B (es) Análogos de éter fosfolipídico como portadores de fármacos dirigidos a cáncer.
GT201500334A (es) Compuestos de 3,4- dihidroisoquinolin-2-(1h)-ilo
PE20211782A1 (es) Compuestos de 5-cloro-2-difluorometoxifenil pirazolopirimidina, composiciones y metodos de uso de los mismos
CO2017009994A2 (es) Nuevos compuestos y derivados de sulfonimidoilpurinona para el tratamiento y profilaxis de infecciones víricas
PE20141380A1 (es) Imidazopiridazinas como inhibidores de quinasa akt
MA38645B1 (fr) Nouveaux inhibiteurs de cyp17/antiandrogènes
PE20161323A1 (es) Compuestos de triazolopiridina, composiciones y metodos de uso de los mismos
WO2013072528A3 (en) Substituted n-(tetrazol-5-yl)- and n-(triazol-5-yl)pyridin-3-yl-carboxamide compounds and their use as herbicides
CU20150175A7 (es) Compuestos inhibidores de la mps-1 quinasa, y las composiciones farmacéuticas y combinaciones farmacéuticas que los contienen
MX2016004841A (es) Compuestos de pirimidina substituidos y su uso como inhibidores de la tirosina cinasa del bazo (syk).
PE20141021A1 (es) DERIVADOS DE TIENO [2,3-d] PIRIMIDINA COMO INHIBIDORES DEL CANAL DE POTASIO

Legal Events

Date Code Title Description
FG Grant, registration