RU2018103881A - Циклические пуриновые динуклеотиды в качестве модуляторов sting - Google Patents
Циклические пуриновые динуклеотиды в качестве модуляторов sting Download PDFInfo
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- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title 2
- 150000003839 salts Chemical class 0.000 claims 44
- 150000001875 compounds Chemical class 0.000 claims 36
- 239000000203 mixture Substances 0.000 claims 14
- 241000124008 Mammalia Species 0.000 claims 7
- 239000000427 antigen Substances 0.000 claims 6
- 230000000890 antigenic effect Effects 0.000 claims 6
- 102000036639 antigens Human genes 0.000 claims 6
- 108091007433 antigens Proteins 0.000 claims 6
- 241000725303 Human immunodeficiency virus Species 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 2
- 208000000260 Warts Diseases 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 208000026935 allergic disease Diseases 0.000 claims 2
- 230000009285 allergic inflammation Effects 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 230000002163 immunogen Effects 0.000 claims 2
- 239000003022 immunostimulating agent Substances 0.000 claims 2
- 230000004054 inflammatory process Effects 0.000 claims 2
- 206010022000 influenza Diseases 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 201000010153 skin papilloma Diseases 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 229960005486 vaccine Drugs 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
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- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- C07F9/02—Phosphorus compounds
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Claims (113)
1. Соединение формулы (VI):
где:
X51 представляет собой O или S;
X52 представляет собой O;
R51 представляет собой OH, и R52 представляет собой NH2, или R51 представляет собой NH2, и R52 представляет собой H;
R53 представляет собой OH, и R54 представляет собой NH2, или R53 представляет собой NH2, и R54 представляет собой H;
R55 выбирают из: F, OH и OC(O)R47;
R56 представляет собой F;
R58 и R59 независимо выбирают из: H, CH2OC(O)R57 , CH2OCO2R57, CH2CH2SC(O)R57 и CH2CH2SSCH2R57;
где R57 выбирают из: арила, гетероарила, гетероциклоалкила, циклоалкила, C1-20алкила и C1-20алкила, замещенного 1-5 заместителями, независимо выбранными из: арила, циклоалкила, гидрокси и F;
при условии, что если X51 представляет собой O, то, по меньшей мере, один из R58 и R59 не представляет собой H,
или его фармацевтически приемлемая соль.
2. Соединение по п. 1 или его фармацевтически приемлемая соль,
где:
R55 выбирают из: F и OH, и
X51 представляет собой O.
3. Соединение по п. 2 или его фармацевтически приемлемая соль,
где:
R55 представляет собой OH, и
X51 представляет собой O.
4. Соединение по п. 1, выбранное из:
или его фармацевтически приемлемая соль.
5. Соединение по п. 4, которое представляет собой:
или его фармацевтически приемлемая соль.
6. Соединение по п. 4, которое представляет собой:
или его фармацевтически приемлемая соль.
7. Соединение по п. 4, которое представляет собой:
или его фармацевтически приемлемая соль.
8. Соединение по п. 4, которое представляет собой:
или его фармацевтически приемлемая соль.
9. Фармацевтическая композиция, содержащая соединение по п. 1 или его фармацевтически приемлемую соль и один или более фармацевтически приемлемых эксципиентов.
10. Способ лечения болезненного состояния, выбранного из воспаления, аллергических заболеваний, аутоиммунных заболеваний, вируса иммунодефицита человека (HIV), инфекционных заболеваний, злокачественной опухоли и предраковых синдромов, у нуждающегося в этом млекопитающего, который включает введение такому млекопитающему терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
11. Способ по п. 10, где млекопитающее представляет собой человека.
12. Композиция, содержащая соединение по п. 1 или его фармацевтически приемлемую соль и антиген или антигенную композицию.
13. Вакцинная композиция, содержащая антиген или антигенную композицию и соединение по п. 1 или его фармацевтически приемлемую соль.
14. Иммуногенная композиция, содержащая антиген или антигенную композицию и соединение по п. 1 или его фармацевтически приемлемую соль.
15. Композиция, содержащая соединение по п. 1 или его фармацевтически приемлемую соль и одно или несколько иммуностимулирующих агентов.
16. Способ лечения заболевания, выбранного из: HBV, HCV, гриппа, кожных бородавок, рассеянного склероза и аллергического воспаления, у нуждающегося в этом человека, который включает введение такому млекопитающему терапевтически эффективного количества соединения или его фармацевтически приемлемой соли по п. 1.
17. Соединение по п. 1 или его фармацевтически приемлемая соль, где:
R55 выбирают из: F и OH; и
X51 представляет собой S.
18. Соединение по п. 1 или его фармацевтически приемлемая соль, где:
R55 представляет собой OH; и
X51 представляет собой S.
19. Соединение по п. 1, выбранное из:
или его фармацевтически приемлемой соли;
или его фармацевтически приемлемой соли;
или его фармацевтически приемлемой соли;
фармацевтически приемлемой соли
фармацевтически приемлемой соли
фармацевтически приемлемой соли
или его фармацевтически приемлемой соли; и
или его фармацевтически приемлемой соли.
20. Соединение, имеющее следующую структуру:
или его фармацевтически приемлемая соль.
21. Соединение, которое представляет собой:
22. Фармацевтически приемлемая соль соединения по п. 20, которое представляет собой:
23. Соединение по п. 20, которое представляет собой:
или его фармацевтически приемлемая соль.
24. Соединение, которое представляет собой:
25. Фармацевтически приемлемая соль соединения по п. 20, которое представляет собой:
26. Соединение по п. 20, которое представляет собой:
или его фармацевтически приемлемая соль.
27. Соединение, которое представляет собой:
28. Фармацевтически приемлемая соль соединения по п. 20, которое представляет собой:
29. Фармацевтическая композиция, содержащая соединение по п. 20 или его фармацевтически приемлемую соль и один или более фармацевтически приемлемых эксципиентов.
30. Способ лечения болезненного состояния, выбранного из: воспаления, аллергических заболеваний, аутоиммунных заболеваний, вируса иммунодефицита человека (HIV), инфекционных заболеваний, злокачественной опухоли и предраковых синдромов, у нуждающегося в этом млекопитающего, который включает введение такому млекопитающему терапевтически эффективного количества соединения или его фармацевтически приемлемой соли по п. 20.
31. Способ по п. 30, где млекопитающее представляет собой человека.
32. Композиция, содержащая соединение по п. 20 или его фармацевтически приемлемую соль и антиген или антигенную композицию.
33. Вакцинная композиция, содержащая антиген или антигенную композицию и соединение по п. 20 или его фармацевтически приемлемую соль.
34. Иммуногенная композиция, содержащая антиген или антигенную композицию и соединение по п. 20 или его фармацевтически приемлемую соль.
35. Композиция, содержащая соединение по п. 20 или его фармацевтически приемлемую соль и одно или несколько иммуностимулирующих агентов.
36. Способ лечения заболевания, выбранного из: HBV, HCV, гриппа, кожных бородавок, рассеянного склероза и аллергического воспаления, у нуждающегося в этом человека, который включает введение такому человеку терапевтически эффективного количества соединения или его фармацевтически приемлемой соли по п. 20.
37. Соединение по п. 1, выбранное из:
или его фармацевтически приемлемой соли;
или его фармацевтически приемлемой соли;
или его фармацевтически приемлемой соли;
или его фармацевтически приемлемой соли; и
или его фармацевтически приемлемой соли.
38. Соединение по п. 1 или его фармацевтически приемлемая соль, где:
R58 и R59 представляют собой H, и
X51 представляет собой S.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562262668P | 2015-12-03 | 2015-12-03 | |
| US62/262,668 | 2015-12-03 | ||
| US201662299253P | 2016-02-24 | 2016-02-24 | |
| US62/299,253 | 2016-02-24 | ||
| US201662299704P | 2016-02-25 | 2016-02-25 | |
| US62/299,704 | 2016-02-25 | ||
| US201662327579P | 2016-04-26 | 2016-04-26 | |
| US62/327,579 | 2016-04-26 | ||
| US201662332517P | 2016-05-06 | 2016-05-06 | |
| US62/332,517 | 2016-05-06 | ||
| PCT/IB2016/057265 WO2017093933A1 (en) | 2015-12-03 | 2016-12-01 | Cyclic purine dinucleotides as modulators of sting |
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| RU2020113165A Division RU2020113165A (ru) | 2015-12-03 | 2016-12-01 | Циклические пуриновые динуклеотиды в качестве модуляторов sting |
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| RU2018103881A3 RU2018103881A3 (ru) | 2019-08-02 |
| RU2018103881A true RU2018103881A (ru) | 2019-08-02 |
| RU2722019C2 RU2722019C2 (ru) | 2020-05-26 |
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| RU2018103881A RU2722019C2 (ru) | 2015-12-03 | 2016-12-01 | Циклические пуриновые динуклеотиды в качестве модуляторов sting |
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| US (4) | US9718848B2 (ru) |
| EP (2) | EP3366691A1 (ru) |
| JP (1) | JP6411676B2 (ru) |
| KR (1) | KR101949108B1 (ru) |
| CN (1) | CN107849084B (ru) |
| AU (1) | AU2016362697B2 (ru) |
| CA (1) | CA3006930A1 (ru) |
| CL (1) | CL2018001484A1 (ru) |
| CO (1) | CO2017013310A2 (ru) |
| CR (1) | CR20180286A (ru) |
| ES (1) | ES2863225T3 (ru) |
| HK (1) | HK1250032A1 (ru) |
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| PE (1) | PE20181297A1 (ru) |
| PH (1) | PH12017502332A1 (ru) |
| RU (2) | RU2020113165A (ru) |
| TW (1) | TWI704154B (ru) |
| UY (1) | UY37007A (ru) |
| WO (1) | WO2017093933A1 (ru) |
| ZA (1) | ZA201801631B (ru) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11919917B2 (en) | 2018-10-11 | 2024-03-05 | Ono Pharmaceutical Co., Ltd. | Sting agonistic compound |
| US12152049B2 (en) | 2018-10-11 | 2024-11-26 | Ono Pharmaceutical Co., Ltd. | STING agonistic compound |
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