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RU2018106886A - Комбинированные терапии для лечения рака - Google Patents

Комбинированные терапии для лечения рака Download PDF

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RU2018106886A
RU2018106886A RU2018106886A RU2018106886A RU2018106886A RU 2018106886 A RU2018106886 A RU 2018106886A RU 2018106886 A RU2018106886 A RU 2018106886A RU 2018106886 A RU2018106886 A RU 2018106886A RU 2018106886 A RU2018106886 A RU 2018106886A
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inhibitor
cyclin
dependent kinase
cancer
dna methyltransferase
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RU2018106886A
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RU2018106886A3 (ru
RU2759963C2 (ru
Inventor
Дэвид Дж. БИРСС
Стивен Л. УОРНЕР
Адам СИДДИКВИ-ДЖАИН
Клиффорд Дж. УОТКОТТ
Вонтак КИМ
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Толеро Фармасьютикалз, Инк.
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    • 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
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    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • A61K31/452—Piperidinium derivatives
    • 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
    • A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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Claims (22)

1. Способ лечения рака у млекопитающего, в этом нуждающегося, способ включает введение млекопитающему терапевтически эффективного количества следующих терапевтических агентов
(i) ингибитор циклин-зависимой киназы; и
(ii) ингибитор метилтрансферазы ДНК.
2. Способ по п.1, в котором ингибитор циклин-зависимой киназы ингибирует Cdk7, Cdk9 или обе.
3. Способ по п.1, в котором ингибитор циклин-зависимой киназы ингибирует экспрессию MCL-1.
4. Способ по п.1, в котором ингибитор циклин-зависимой киназы представляет собой альвоцидиб или динациклиб или их фармацевтически приемлемые соли.
5. Способ по п.1, в котором ингибитор метилтрансферазы ДНК активирует апоптоз.
6. Способ по п.1, в котором ингибитор метилтрансферазы ДНК представляет собой нуклеозидный аналог.
7. Способ по п.1, в котором ингибитор метилтрансферазы ДНК представляет собой азануклеозид.
8. Способ по п.7, в котором азануклеозид представляет собой азацитидин или децитабин или их фармацевтически приемлемые соли.
9. Способ по любому из пп.1-8, в котором ингибитор циклин-зависимой киназы вводится млекопитающему перед введением ингибитора метилтрансферазы ДНК.
10. Способ по п.9, в котором ингибитор метилтрансферазы ДНК вводится в период примерно от 24 до 48 часов после введения ингибитора циклин-зависимой киназы.
11. Способ по любому из пп.1-8, в котором ингибитор метилтрансферазы ДНК вводится млекопитающему до введения ингибитора циклин-зависимой киназы.
12. Способ по любому из пп.1-11, в котором рак представляет собой гематологический рак.
13. Способ по п.12, в котором гематологический рак является одним из представленных в списке: острая миелогенная лейкемия (AML), множественная миелома, фолликулярная лимфома, острая лимфобластная лейкемия (ALL), хроническая лимфоцитарная лейкемия (CLL) и неходжкинская лимфома.
14. Способ по п.13, в котором гематологический рак представляет собой острую миелогенную лейкемию (AML).
15. Способ по п.12, в котором гематологический рак представляет собой миелодиспластический синдром (MDS).
16. Набор, содержащий ингибитор циклин-зависимой киназы, ингибитор метилтрансферазы ДНК и инструкции для введения ингибитора циклин-зависимой киназы и ингибитора метилтрансферазы ДНК млекопитающему, нуждающемуся в лечении рака.
17. Набор по п.16, в котором ингибитор циклин-зависимой киназы является таким, как определено в любом из пп.2-4.
18. Набор по любому из пп.16 или 17, в котором ингибитор метилтрансферазы ДНК является таким, как определено в любом из пп.5-8.
19. Набор по любому из пп.16-18, в котором рак является таким, как определено в любом из пп.12-15.
20. Фармацевтическая композиция, содержащая фармацевтически приемлемый носитель или эксципиент, ингибитор циклин-зависимой киназы и ингибитор метилтрансферазы ДНК.
RU2018106886A 2015-08-03 2016-08-03 Комбинированные терапии для лечения рака RU2759963C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562200499P 2015-08-03 2015-08-03
US62/200,499 2015-08-03
PCT/US2016/045423 WO2017024073A1 (en) 2015-08-03 2016-08-03 Combination therapies for treatment of cancer

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RU2018106886A true RU2018106886A (ru) 2019-09-05
RU2018106886A3 RU2018106886A3 (ru) 2019-12-31
RU2759963C2 RU2759963C2 (ru) 2021-11-19

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US (4) US10568887B2 (ru)
EP (1) EP3331510A4 (ru)
JP (2) JP7083497B2 (ru)
KR (1) KR20180034538A (ru)
CN (1) CN108289861B (ru)
AU (1) AU2016301315C1 (ru)
BR (1) BR112018002427A8 (ru)
CA (1) CA2993659A1 (ru)
IL (1) IL257073A (ru)
MX (1) MX2018001289A (ru)
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