RU2018103454A - Соединения бензоксазепиноксазолидинонов и способы применения - Google Patents
Соединения бензоксазепиноксазолидинонов и способы применения Download PDFInfo
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- RU2018103454A RU2018103454A RU2018103454A RU2018103454A RU2018103454A RU 2018103454 A RU2018103454 A RU 2018103454A RU 2018103454 A RU2018103454 A RU 2018103454A RU 2018103454 A RU2018103454 A RU 2018103454A RU 2018103454 A RU2018103454 A RU 2018103454A
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- RU
- Russia
- Prior art keywords
- cancer
- breast cancer
- oxooxazolidin
- oxazepin
- dihydrobenzo
- Prior art date
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Classifications
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
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- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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Claims (33)
1. Соединение, выбранное из соединения формулы I
и его стереоизомеры, геометрические изомеры, таутомеры и фармацевтически приемлемые соли, где:
R1 выбран из -CH3, -CH2CH3, циклопропила и циклобутила;
R2 выбран из -CH3, -CHF2, -CH2F и -CF3.
2. Соединение по п. 1, где R1 представляет собой CH3 или циклопропил.
3. Соединение по п. 1 или 2, где R2 представляет собой -CHF2.
4. Соединение, выбранное из
(S)-2-((2-((S)-4-(дифторметил)-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)пропанамида;
(S)-2-циклобутил-2-((2-((R)-4-метил-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)ацетамида;
(S)-2-циклопропил-2-((2-((S)-4-(дифторметил)-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)ацетамида;
(S)-2-циклопропил-2-((2-((R)-4-метил-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)ацетамида;
(S)-2-циклопропил-2-((2-((S)-4-(фторметил)-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)ацетамида;
(S)-2-((2-((S)-4-(фторметил)-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)пропанамида;
(S)-2-((2-((S)-4-(дифторметил)-2-оксооксазолидин-3-ил)-5,6-дигидробензо[f]имидазо[1,2-d][1,4]оксазепин-9-ил)амино)бутанамид.
5. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-4 и фармацевтически приемлемый носитель, вещество, способствующее скольжению, разбавитель или эксципиент.
6. Фармацевтическая композиция по п. 5, где фармацевтически приемлемый носитель, вещество, способствующее скольжению, разбавитель или эксципиент выбран из диоксида кремния, порошкообразной целлюлозы, микрокристаллической целлюлозы, стеаратов металлов, алюмосиликата натрия, бензоата натрия, карбоната кальция, силиката кальция, кукурузного крахмала, карбоната магния, не содержащего асбеста талька, стеаровета С, крахмала, крахмала 1500, лаурилсульфата магния, оксида магния и их комбинаций.
7. Способ приготовления фармацевтической композиции, включающий комбинирование соединения по любому из пп. 1-4 с фармацевтически приемлемым носителем, веществом, способствующим скольжению, разбавителем или эксципиентом.
8. Способ лечения рака у пациента с диагнозом рак, включающий введение указанному пациенту терапевтически эффективного количества соединения по любому из пп. 1-4, при этом данный рак выбран из рака молочной железы и немелкоклеточного рака легкого.
9. Способ по п. 8, дополнительно включающий введение пациенту дополнительного терапевтического агента, выбранного из 5-фторурацила (5-FU), доцетаксела, эрибулина, гемцитабина, кобиметиниба, ипатасертиба, паклитаксела, тамоксифена, фулвестранта, GDC-0810, дексаметазона, палбоциклиба, бевацизумаба, пертузумаба, трастузумаба эмтанзина, трастузумаба и летрозола.
10. Способ по п. 8, где рак представляет собой рак молочной железы.
11. Способ по п. 10, где рак молочной железы представляет собой положительный по рецепторам эстрогенов (ER+) рак молочной железы.
12. Способ по п. 10, где раком молочной железы является рак базального или люминального подтипа.
13. Способ по п. 8, где при данном виде рака экспрессируется PIK3CA (от англ. phosphatidylinositol-3-kinase, catalytic subunit alpha - каталитическая альфа-субъединица фосфатидилинозитол-3-киназы) с мутацией, выбранной из E542K, E545K, Q546R, H1047L и H1047R.
14. Способ по п. 8, где при данном виде рака экспрессируется мутантная форма PTEN (от англ. phosphatase and tensin homolog - гомолог фосфатазы и тензина).
15. Способ по п. 10, где данный вид рака представляет собой HER2 (от англ. human epidermal growth factor receptor 2 - рецептор эпидермального фактора роста человека 2 типа)-положительный рак.
16. Способ по п. 10, где пациент является HER2-отрицательным, ER(рецептор эстрогенов)-отрицательным и PR(рецептор прогестерона отрицательным.
17. Набор для терапевтического лечения рака молочной железы, содержащий
a) фармацевтическую композицию по п. 5 или 6; и
b) инструкции для применения при терапевтическом лечении рака молочной железы.
18. Применение соединения по любому из пп. 1-4 для лечения рака у пациента, причем данный рак выбран из рака молочной железы и немелкоклеточного рака легкого.
19. Применение соединения по любому из пп. 1-4 для изготовления лекарственного средства для лечения рака у пациента, причем данный рак выбран из рака молочной железы и немелкоклеточного рака легкого.
20. Соединение по любому из пп. 1-4 для применения для лечения рака у пациента, причем данный рак выбран из рака молочной железы и немелкоклеточного рака легкого.
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| UY34632A (es) | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
| BR112014021935A2 (pt) | 2012-03-05 | 2019-09-24 | Gilead Calistoga Llc | formas polimórficas de (s)-2(l-(9h-purin-6-ilamino)propil)-5-fluoro-3-fenilquinazolina-4(3h)ona |
| US9751153B2 (en) * | 2012-03-30 | 2017-09-05 | Brigham Young University | Effort modulation for process control of friction stir operations |
| SG10201706196XA (en) | 2012-06-08 | 2017-08-30 | Hoffmann La Roche | Mutant selectivity and combinations of a phosphoinositide 3 kinase inhibitor compound and chemotherapeutic agents for the treatment of cancer |
| CN108929333A (zh) * | 2013-03-13 | 2018-12-04 | 豪夫迈·罗氏有限公司 | 制备苯并氧氮杂*化合物的方法 |
| JP6260967B2 (ja) * | 2013-11-06 | 2018-01-17 | 国立大学法人京都大学 | 放射性ヨウ素標識化合物、及び、これを含む放射性医薬 |
| CN112047960B (zh) | 2015-07-02 | 2024-08-02 | 豪夫迈·罗氏有限公司 | 苯并氧氮杂䓬噁唑烷酮化合物及其使用方法 |
| EP3317283B1 (en) | 2015-07-02 | 2019-04-03 | H. Hoffnabb-La Roche Ag | Benzoxazepin oxazolidinone compounds and methods of use |
| SG10201913961PA (en) | 2016-12-15 | 2020-03-30 | Hoffmann La Roche | Process for the preparation of (s)-2-((2-((s)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino) propanamide |
| PL3615541T3 (pl) * | 2017-04-28 | 2025-06-23 | F. Hoffmann-La Roche Ag | Postaci polimorficzne i postaci stałe (S)-2-((2-((S)-4-(difluorometylo)-2-oksooksazolidyn-3- ylo)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oksazepin-9-ylo)amino)propanoamidu i sposoby wytwarzania |
| MX2021000847A (es) | 2018-07-23 | 2021-03-26 | Hoffmann La Roche | Procedimientos para el tratamiento del cancer con el inhibidor de pi3k, gdc 0077. |
| EP3863618A1 (en) | 2018-10-08 | 2021-08-18 | F. Hoffmann-La Roche AG | Methods of treating cancer with pi3k alpha inhibitors and metformin |
| KR20220108085A (ko) | 2019-12-03 | 2022-08-02 | 제넨테크, 인크. | 유방암 치료를 위한 병용 요법 |
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