WO2015018522A1 - Inhibiteur de bromodomaine bet présentant une synergie avec plusieurs agents anti-cancéreux dans des modèles cliniques de lymphome diffus de cellule b de grande taille (dlbcl) - Google Patents

Inhibiteur de bromodomaine bet présentant une synergie avec plusieurs agents anti-cancéreux dans des modèles cliniques de lymphome diffus de cellule b de grande taille (dlbcl) Download PDF

Info

Publication number
WO2015018522A1
WO2015018522A1 PCT/EP2014/002165 EP2014002165W WO2015018522A1 WO 2015018522 A1 WO2015018522 A1 WO 2015018522A1 EP 2014002165 W EP2014002165 W EP 2014002165W WO 2015018522 A1 WO2015018522 A1 WO 2015018522A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
carbon number
solid dispersion
thienotriazolodiazepine
alkyl
Prior art date
Application number
PCT/EP2014/002165
Other languages
English (en)
Inventor
Francesco Bertoni
Giorgio Inghirami
Original Assignee
Oncoethix Sa
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
Application filed by Oncoethix Sa filed Critical Oncoethix Sa
Publication of WO2015018522A1 publication Critical patent/WO2015018522A1/fr

Links

Classifications

    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/436—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 oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • 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
    • 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
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne procédé de traitement de lymphome diffus de cellule B de grande taille chez un mammifère, comprenant l'étape consistant à administrer une quantité pharmaceutiquement acceptable d'une combinaison de médicaments anticancéreux à un patient, laquelle combinaison comprend un premier composé et un second composé; le premier composé est choisi dans le groupe comprenant un inhibiteur de mTOR, un inhibiteur de BTK, un inhibiteur de HDAC, un anticorps monoclonal anti CD20, un agent d'hypométhylation et un immunomodulateur; le second composant consiste en un composé de thiènotriazolodiazépine correpondant à la formule (1) où : R1 est alkyle comprenant 1-4 atomes de carbone; R2 est un atome d'hydrogène; un atome halogène; ou un alkyle comprenant 1-4 atomes de carbone éventuellement substitué par un atome halogène ou un groupe hydroxyle; R3 est un atome halogène; un phényle éventuellement substitué par un atome halogène, un alkyle comprenant 1-4 atomes de carbone, un alcoxy comprenant 1-4 atomes de carbone ou cyano; — NR5— (CH2)m— R6 où R5 est un atome d'hydrogène ou un alkyle comprenant 1-4 atomes de carbone, m est un nombre entier de 0-4, et R6 est phényle ou pyrdiyle éventuellement substitué par un atome halogène; ou -NR7— CO— (CH2)n— R8 où R7 est un atome d'hydrogène ou un alkyle comprenant 1-4 atomes de carbone, n est un nombre entier de 0-2 et R8 est un phényle ou pyrdiyle éventuellement substitué par un atome halogène, et R4 est — (CH2)a— CO— NH— R9 où a est un nombre entier de 1-4 et R9 est un alkyle comprenant 1-4 atomes de carbone; hydroxyalkyle comprenant 1-4 atomes de carbone; alcoxy comprenant 1-4 atomes de carbone; ou phényle ou pyrdiyle éventuellement substitué par un alkyle comprenant 1-4 atomes de carbone, alcoxy comprenant 1-4 atomes de carbone, amino ou un groupe hydroxyle ou — (CH2)b— COOR10 où b est un nombre entier de 1-4 et R10 est un alkyle comprenant 1-4 atomes de carbone; ou un sel pharmaceutiquement acceptable de celui-ci ou un hydrate ou solvate de celui-ci.
PCT/EP2014/002165 2013-08-06 2014-08-06 Inhibiteur de bromodomaine bet présentant une synergie avec plusieurs agents anti-cancéreux dans des modèles cliniques de lymphome diffus de cellule b de grande taille (dlbcl) WO2015018522A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201361862752P 2013-08-06 2013-08-06
US201361862772P 2013-08-06 2013-08-06
US61/862,752 2013-08-06
US61/862,772 2013-08-06
US201314619097A 2013-11-27 2013-11-27
US61//909,703 2013-11-27

Publications (1)

Publication Number Publication Date
WO2015018522A1 true WO2015018522A1 (fr) 2015-02-12

Family

ID=52460696

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2014/002165 WO2015018522A1 (fr) 2013-08-06 2014-08-06 Inhibiteur de bromodomaine bet présentant une synergie avec plusieurs agents anti-cancéreux dans des modèles cliniques de lymphome diffus de cellule b de grande taille (dlbcl)

Country Status (1)

Country Link
WO (1) WO2015018522A1 (fr)

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9290504B2 (en) 2011-07-19 2016-03-22 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as Btk inhibitors
WO2016176335A1 (fr) 2015-04-27 2016-11-03 Concert Pharmaceuticals, Inc. Otx-015 deutéré
CN106146352A (zh) * 2015-04-16 2016-11-23 上海医药工业研究院 Idelalisib中间体及其制备方法
WO2017112703A1 (fr) * 2015-12-24 2017-06-29 Celgene Quanticel Research, Inc. Thérapie d'association par inhibiteur de bromodomaine et de protéine extra-terminale
US9718828B2 (en) 2011-07-19 2017-08-01 Merck Sharp & Dohme Corp. BTK Inhibitors
CN107033147A (zh) * 2017-04-25 2017-08-11 东南大学 一种bet/hdac双靶点抑制剂及其制备方法和应用
WO2017059319A3 (fr) * 2015-10-02 2017-10-12 Dana-Farber Cancer Institute, Inc. Polythérapie par inhibiteurs de bromodomaine et blocage de point de contrôle
US9814721B2 (en) 2010-06-03 2017-11-14 Pharmacyclics Llc Use of inhibitors of bruton'S tyrosine kinase (BTK)
EP3137086A4 (fr) * 2014-05-02 2017-12-27 Oncoethix GmbH Methode de traitement de lymphome non hodgkinien resistant, de medulloblastome et/ou de cancer bronchopulmonaire non a petites cellules alk+ a l'aide de composes de thienotriazolodiazepine
WO2018013693A1 (fr) * 2016-07-13 2018-01-18 Celgene Corporation Dispersions solides et co-cristaux comprenant des compositions de 3-(4-amino-1-oxo-1,3-dihydro-iso-indol-2-yl)-pipéridine-2,6-dione et procédés pour les utiliser
US9885086B2 (en) 2014-03-20 2018-02-06 Pharmacyclics Llc Phospholipase C gamma 2 and resistance associated mutations
US9937171B2 (en) 2014-04-11 2018-04-10 Acerta Pharma B.V. Methods of blocking the CXCR-4/SDF-1 signaling pathway with inhibitors of bruton's tyrosine kinase
US9949971B2 (en) 2014-06-17 2018-04-24 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor and/or a JAK-2 inhibitor
WO2018081475A1 (fr) * 2016-10-27 2018-05-03 Celgene Quanticel Research, Inc. Polythérapie par inhibiteur de protéine à bromodomaine et domaine extra-terminal
CN108033961A (zh) * 2015-04-15 2018-05-15 上海方楠生物科技有限公司 一种艾德力布的无定型物及其制备方法
US10124009B2 (en) 2014-10-27 2018-11-13 Tensha Therapeutics, Inc. Bromodomain inhibitors
US10167291B2 (en) 2015-07-02 2019-01-01 Acerta Pharma B.V. Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl) pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide
WO2019020606A1 (fr) * 2017-07-26 2019-01-31 F. Hoffmann-La Roche Ag Polythérapie avec un inhibiteur bet, un inhibiteur bcl-2 et un anticorps anti-cd20
US10328080B2 (en) 2013-12-05 2019-06-25 Acerta Pharma, B.V. Therapeutic combination of PI3K inhibitor and a BTK inhibitor
US10407441B2 (en) 2010-05-14 2019-09-10 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating neoplasia, inflammatory disease and other disorders
US10676484B2 (en) 2010-05-14 2020-06-09 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating leukemia
US10906917B2 (en) 2018-06-13 2021-02-02 Dybly Ag Preparation of condensed triazepine derivatives and their use as BET inhibitors
US10925881B2 (en) 2014-02-28 2021-02-23 Tensha Therapeutics, Inc. Treatment of conditions associated with hyperinsulinaemia
US10954567B2 (en) 2012-07-24 2021-03-23 Pharmacyclics Llc Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK)
US11084793B2 (en) 2014-05-01 2021-08-10 Celgene Quanticel Research, Inc. Inhibitors of lysine specific demethylase-1
US11166951B2 (en) 2014-08-11 2021-11-09 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
US11446309B2 (en) 2013-11-08 2022-09-20 Dana-Farber Cancer Institute, Inc. Combination therapy for cancer using bromodomain and extra-terminal (BET) protein inhibitors
US11666580B2 (en) 2015-08-10 2023-06-06 Dana-Farber Cancer Institute, Inc. Mechanism of resistance to bet bromodomain inhibitors

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1297836A1 (fr) * 2000-06-16 2003-04-02 Mitsubishi Pharma Corporation Compositions permettant de reguler la plage et/ou la vitesse de liberation du ph
EP2239264A1 (fr) * 2007-12-28 2010-10-13 Mitsubishi Tanabe Pharma Corporation Agent antitumoral
WO2011143669A2 (fr) * 2010-05-14 2011-11-17 Dana-Farber Cancer Institute, Inc Compositions et méthodes de traitement des néoplasies, des maladies inflammatoires et d'autres affections
WO2012075456A1 (fr) * 2010-12-02 2012-06-07 Constellation Pharmaceuticals Inhibiteurs de bromodomaines et leurs utilisations
WO2014001356A1 (fr) * 2012-06-25 2014-01-03 Oncoethix Sa Méthode de traitement d'un lymphome à l'aide de composés thiénotriazolodiazépine
WO2014068402A2 (fr) * 2012-09-28 2014-05-08 Oncoethix Sa Formulation pharmaceutique contenant des composés thienotriazolodiazepine

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1297836A1 (fr) * 2000-06-16 2003-04-02 Mitsubishi Pharma Corporation Compositions permettant de reguler la plage et/ou la vitesse de liberation du ph
EP2239264A1 (fr) * 2007-12-28 2010-10-13 Mitsubishi Tanabe Pharma Corporation Agent antitumoral
WO2011143669A2 (fr) * 2010-05-14 2011-11-17 Dana-Farber Cancer Institute, Inc Compositions et méthodes de traitement des néoplasies, des maladies inflammatoires et d'autres affections
WO2012075456A1 (fr) * 2010-12-02 2012-06-07 Constellation Pharmaceuticals Inhibiteurs de bromodomaines et leurs utilisations
WO2014001356A1 (fr) * 2012-06-25 2014-01-03 Oncoethix Sa Méthode de traitement d'un lymphome à l'aide de composés thiénotriazolodiazépine
WO2014068402A2 (fr) * 2012-09-28 2014-05-08 Oncoethix Sa Formulation pharmaceutique contenant des composés thienotriazolodiazepine

Cited By (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10676484B2 (en) 2010-05-14 2020-06-09 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating leukemia
US10407441B2 (en) 2010-05-14 2019-09-10 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating neoplasia, inflammatory disease and other disorders
US10751342B2 (en) 2010-06-03 2020-08-25 Pharmacyclics Llc Use of inhibitors of Bruton's tyrosine kinase (Btk)
US10653696B2 (en) 2010-06-03 2020-05-19 Pharmacyclics Llc Use of inhibitors of bruton's tyrosine kinase (BTK)
US10004745B2 (en) 2010-06-03 2018-06-26 Pharmacyclics Llc Use of inhibitors of Bruton'S tyrosine kinase (Btk)
US11672803B2 (en) 2010-06-03 2023-06-13 Pharmacyclics Llc Use of inhibitors of Brutons tyrosine kinase (Btk)
US10004746B2 (en) 2010-06-03 2018-06-26 Pharmacyclics Llc Use of inhibitors of Bruton's tyrosine kinase (Btk)
US10016435B2 (en) 2010-06-03 2018-07-10 Pharmacyclics Llc Use of inhibitors of Bruton's tyrosine kinase (Btk)
US10478439B2 (en) 2010-06-03 2019-11-19 Pharmacyclics Llc Use of inhibitors of bruton's tyrosine kinase (Btk)
US9814721B2 (en) 2010-06-03 2017-11-14 Pharmacyclics Llc Use of inhibitors of bruton'S tyrosine kinase (BTK)
US9758524B2 (en) 2011-07-19 2017-09-12 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as Btk inhibitors
US9290504B2 (en) 2011-07-19 2016-03-22 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as Btk inhibitors
US10239883B2 (en) 2011-07-19 2019-03-26 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as BTK inhibitors
US9790226B2 (en) 2011-07-19 2017-10-17 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as BtK inhibitors
US10934296B2 (en) 2011-07-19 2021-03-02 Merck Sharp & Dohme B.V. 4-imidazopyridazin-1-yl-benzamides as Btk inhibitors
US9718828B2 (en) 2011-07-19 2017-08-01 Merck Sharp & Dohme Corp. BTK Inhibitors
US10954567B2 (en) 2012-07-24 2021-03-23 Pharmacyclics Llc Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK)
US11446309B2 (en) 2013-11-08 2022-09-20 Dana-Farber Cancer Institute, Inc. Combination therapy for cancer using bromodomain and extra-terminal (BET) protein inhibitors
US10328080B2 (en) 2013-12-05 2019-06-25 Acerta Pharma, B.V. Therapeutic combination of PI3K inhibitor and a BTK inhibitor
US10925881B2 (en) 2014-02-28 2021-02-23 Tensha Therapeutics, Inc. Treatment of conditions associated with hyperinsulinaemia
US9885086B2 (en) 2014-03-20 2018-02-06 Pharmacyclics Llc Phospholipase C gamma 2 and resistance associated mutations
US9937171B2 (en) 2014-04-11 2018-04-10 Acerta Pharma B.V. Methods of blocking the CXCR-4/SDF-1 signaling pathway with inhibitors of bruton's tyrosine kinase
US11084793B2 (en) 2014-05-01 2021-08-10 Celgene Quanticel Research, Inc. Inhibitors of lysine specific demethylase-1
EP3137086A4 (fr) * 2014-05-02 2017-12-27 Oncoethix GmbH Methode de traitement de lymphome non hodgkinien resistant, de medulloblastome et/ou de cancer bronchopulmonaire non a petites cellules alk+ a l'aide de composes de thienotriazolodiazepine
US9949971B2 (en) 2014-06-17 2018-04-24 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor and/or a JAK-2 inhibitor
US11654143B2 (en) 2014-08-11 2023-05-23 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
US11166951B2 (en) 2014-08-11 2021-11-09 Acerta Pharma B.V. Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
US10124009B2 (en) 2014-10-27 2018-11-13 Tensha Therapeutics, Inc. Bromodomain inhibitors
CN108033961A (zh) * 2015-04-15 2018-05-15 上海方楠生物科技有限公司 一种艾德力布的无定型物及其制备方法
CN106146352A (zh) * 2015-04-16 2016-11-23 上海医药工业研究院 Idelalisib中间体及其制备方法
WO2016176335A1 (fr) 2015-04-27 2016-11-03 Concert Pharmaceuticals, Inc. Otx-015 deutéré
US11059829B2 (en) 2015-07-02 2021-07-13 Acerta Pharma B.V. Crystal forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide maleate
US11820777B2 (en) 2015-07-02 2023-11-21 Acerta Pharma B.V. Crystal forms of (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide
US10167291B2 (en) 2015-07-02 2019-01-01 Acerta Pharma B.V. Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl) pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide
US11666580B2 (en) 2015-08-10 2023-06-06 Dana-Farber Cancer Institute, Inc. Mechanism of resistance to bet bromodomain inhibitors
WO2017059319A3 (fr) * 2015-10-02 2017-10-12 Dana-Farber Cancer Institute, Inc. Polythérapie par inhibiteurs de bromodomaine et blocage de point de contrôle
JP2018530554A (ja) * 2015-10-02 2018-10-18 ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド ブロモドメイン阻害薬及びチェックポイント阻害薬による併用療法
WO2017112703A1 (fr) * 2015-12-24 2017-06-29 Celgene Quanticel Research, Inc. Thérapie d'association par inhibiteur de bromodomaine et de protéine extra-terminale
WO2018013693A1 (fr) * 2016-07-13 2018-01-18 Celgene Corporation Dispersions solides et co-cristaux comprenant des compositions de 3-(4-amino-1-oxo-1,3-dihydro-iso-indol-2-yl)-pipéridine-2,6-dione et procédés pour les utiliser
US10881655B2 (en) 2016-10-27 2021-01-05 Celgene Quanticel Research, Inc. Bromodomain and extra-terminal protein inhibitor combination therapy
US10166227B2 (en) 2016-10-27 2019-01-01 Celgene Quanticel Research, Inc. Bromodomain and extra-terminal protein inhibitor combination therapy
US11464771B2 (en) 2016-10-27 2022-10-11 Celgene Quanticel Research, Inc. Bromodomain and extra-terminal protein inhibitor combination therapy
WO2018081475A1 (fr) * 2016-10-27 2018-05-03 Celgene Quanticel Research, Inc. Polythérapie par inhibiteur de protéine à bromodomaine et domaine extra-terminal
US10576075B2 (en) 2016-10-27 2020-03-03 Celgene Quanticel Research, Inc. Bromodomain and extra-terminal protein inhibitor combination therapy
CN107033147A (zh) * 2017-04-25 2017-08-11 东南大学 一种bet/hdac双靶点抑制剂及其制备方法和应用
WO2019020606A1 (fr) * 2017-07-26 2019-01-31 F. Hoffmann-La Roche Ag Polythérapie avec un inhibiteur bet, un inhibiteur bcl-2 et un anticorps anti-cd20
CN110869391A (zh) * 2017-07-26 2020-03-06 豪夫迈·罗氏有限公司 用BET抑制剂,Bcl-2抑制剂和抗CD20抗体的组合疗法
US10906917B2 (en) 2018-06-13 2021-02-02 Dybly Ag Preparation of condensed triazepine derivatives and their use as BET inhibitors
US11708374B2 (en) 2018-06-13 2023-07-25 Worg Pharmaceuticals (Zhejiang) Co., Ltd. Preparation of condensed triazepine derivatives and their use as BET inhibitors

Similar Documents

Publication Publication Date Title
WO2015018522A1 (fr) Inhibiteur de bromodomaine bet présentant une synergie avec plusieurs agents anti-cancéreux dans des modèles cliniques de lymphome diffus de cellule b de grande taille (dlbcl)
AU2013340483B2 (en) Pharmaceutical formulation containing thienotriazolodiazepine compounds
EP3030242A1 (fr) Procédé de traitement de lymphome diffus à grande cellules b (ldgcb) au moyen d'un inhibiteur de bromodomaine de bet
AU2015252940A1 (en) Method of treating resistant non-Hodgkin lymphoma, medulloblastoma, and/or ALK+non-small cell lung cancer using thienotriazolodiazepine compounds
US9956228B2 (en) Method of treating acute myeloid leukemia and/or acute lymphoblastic leukemia using thienotriazolodiazepine compounds
WO2015169953A1 (fr) Méthode de traitement d'un gliome à l'aide de composés thiénotriazolodiazépine
WO2015169951A1 (fr) Méthode de traitement du cancer du sein triple négatif à l'aide de composés de thiénotriazolodiazépine
EP3074018A1 (fr) Méthode de traitement de la leucémie au moyen d'une formulation pharmaceutique contenant des composés de thiénotriazolodiazépine
US20170281642A1 (en) Methods of treating acute myeloid leukemia or acute lymphoid leukemia using pharmaceutical compositions containing thienotriazolodiazepine compounds
WO2015018520A1 (fr) Inhibiteur bet-brd représentant un nouvel agent pour un lymphome anaplasique à grandes cellules alk positif
US9795612B2 (en) Pharmaceutical formulation containing thienotriazolodiazepine compounds
AU2015273032A1 (en) Method of treating non-small cell lung cancer and/or small cell lung cancer using thienotriazolodiazepine compounds
US9820992B2 (en) Method of treating non-small-cell lung cancer using pharmaceutical formulation containing thienotriazolodiazepine compounds
WO2015018523A1 (fr) Nouvel inhibiteur de bet-brd pour le traitement de tumeurs solides
WO2015168587A1 (fr) Procédé de traitement de myélome multiple résistant et de lymphome des cellules du manteau à l'aide de composés de thiénotriazolodiazépine
WO2016026912A1 (fr) Méthode de traitement de lymphomes à l'aide de composés thiénotriazolodiazépine

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14755589

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14755589

Country of ref document: EP

Kind code of ref document: A1