RU2014144309A - Индазольные ингибиторы сигнального пути wnt и их терапевтические применения - Google Patents
Индазольные ингибиторы сигнального пути wnt и их терапевтические применения Download PDFInfo
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- RU2014144309A RU2014144309A RU2014144309A RU2014144309A RU2014144309A RU 2014144309 A RU2014144309 A RU 2014144309A RU 2014144309 A RU2014144309 A RU 2014144309A RU 2014144309 A RU2014144309 A RU 2014144309A RU 2014144309 A RU2014144309 A RU 2014144309A
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- 239000003112 inhibitor Substances 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 42
- 125000001424 substituent group Chemical group 0.000 claims abstract 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 12
- 150000004820 halides Chemical class 0.000 claims abstract 10
- 150000003839 salts Chemical class 0.000 claims abstract 10
- -1 —OR Chemical group 0.000 claims abstract 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 33
- 201000010099 disease Diseases 0.000 claims 17
- 208000035475 disorder Diseases 0.000 claims 16
- 125000000217 alkyl group Chemical group 0.000 claims 14
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims 8
- 102000013814 Wnt Human genes 0.000 claims 7
- 108050003627 Wnt Proteins 0.000 claims 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- 208000011580 syndromic disease Diseases 0.000 claims 4
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- 125000004452 carbocyclyl group Chemical group 0.000 claims 2
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- 230000001404 mediated effect Effects 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
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- 101100317380 Danio rerio wnt4a gene Proteins 0.000 claims 1
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- 101000781981 Homo sapiens Protein Wnt-11 Proteins 0.000 claims 1
- 101000781950 Homo sapiens Protein Wnt-16 Proteins 0.000 claims 1
- 101000804728 Homo sapiens Protein Wnt-2b Proteins 0.000 claims 1
- 101000804792 Homo sapiens Protein Wnt-5a Proteins 0.000 claims 1
- 101000804804 Homo sapiens Protein Wnt-5b Proteins 0.000 claims 1
- 101000855002 Homo sapiens Protein Wnt-6 Proteins 0.000 claims 1
- 101000855004 Homo sapiens Protein Wnt-7a Proteins 0.000 claims 1
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- 101000650149 Homo sapiens Protein Wnt-8b Proteins 0.000 claims 1
- 101000781955 Homo sapiens Proto-oncogene Wnt-1 Proteins 0.000 claims 1
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- 201000010769 Prader-Willi syndrome Diseases 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
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- 102100035331 Protein Wnt-5b Human genes 0.000 claims 1
- 102100020732 Protein Wnt-6 Human genes 0.000 claims 1
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- 102100039470 Protein Wnt-7b Human genes 0.000 claims 1
- 102100039453 Protein Wnt-8a Human genes 0.000 claims 1
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- 101150010310 WNT-4 gene Proteins 0.000 claims 1
- 101150019524 WNT2 gene Proteins 0.000 claims 1
- 208000008383 Wilms tumor Diseases 0.000 claims 1
- 102000052547 Wnt-1 Human genes 0.000 claims 1
- 102000052556 Wnt-2 Human genes 0.000 claims 1
- 108700020986 Wnt-2 Proteins 0.000 claims 1
- 102000052549 Wnt-3 Human genes 0.000 claims 1
- 102000052548 Wnt-4 Human genes 0.000 claims 1
- 108700020984 Wnt-4 Proteins 0.000 claims 1
- 102000043366 Wnt-5a Human genes 0.000 claims 1
- 102000044880 Wnt3A Human genes 0.000 claims 1
- 108700013515 Wnt3A Proteins 0.000 claims 1
- 101100485099 Xenopus laevis wnt2b-b gene Proteins 0.000 claims 1
- 230000001594 aberrant effect Effects 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 201000006288 alpha thalassemia Diseases 0.000 claims 1
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- 201000006902 exudative vitreoretinopathy Diseases 0.000 claims 1
- 230000002538 fungal effect Effects 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
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- 230000002401 inhibitory effect Effects 0.000 claims 1
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- 101150068520 wnt3a gene Proteins 0.000 claims 1
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- Tropical Medicine & Parasitology (AREA)
Abstract
1. Соединение или его фармацевтически приемлемая соль, имеющее структуру, представленную формулой I,где Rпредставляет собой гетероарил-RR;Rвыбирают из группы, состоящей из Н, гетероарил-R, гетероциклил-Rи арил-R;Rвыбирают из группы, состоящей из Н, гетероциклил-R, -NHC(=O)R, -NHSOR, -NRRи (С-алкил)NRR;при условии, что Rи Rне являются оба Н;Rпредставляет собой 1-3 заместителя, выбранные, каждый, из группы, состоящей из Н, С-алкила, галогенида, -CF, -CN, -ORи амино;каждый Rпредставляет собой независимо 1-4 заместителя, выбранные, каждый, из группы, состоящей из Н, С-алкила, галогенида, -CF, -CN, -OR, -С(=O)R, амино и (С-алкил)NRR;каждый Rпредставляет собой независимо 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С-алкила, галогенида, CF, CN, ORи амино;каждый Rпредставляет собой независимо 1-5 заместителей,выбранных, каждый, из группы, включающей Н, С-алкил, галогенид, -CF, -CN, -OR, амино, (С-алкил)NHSOR, -NR(С-алкил)NRRи (С-алкил)NRR;Rпредставляет собой 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С-алкила, галогенида, -CF, -CN, -ORи амино;Rвыбирают из группы, состоящей из С-алкила, гетероарил-R, гетероциклил-R, арил-Rи СН-карбоциклила;Rвыбирают из группы, состоящей из С-алкила, гетероарил-R, гетероциклил-R, арил-Rи карбоциклил-R;каждый Rвыбирают независимо из С-алкила;каждый Rвыбирают независимо из группы, состоящей из Н и С-алкила;каждые Rи Rнеобязательно соединены с образованием пяти- или шестичленного гетероциклила;каждый Rвыбирают независимо из группы, состоящей из Н и С-алкила;Rпредставляет собой 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С-алкила, галогенида, -CF, -CN, -ORи амино;при условии, что формула I не является структурой, выбранной из группы, состоящей из:2. Соединение по п. 1, где Rпредставляет собой пиридин-RR.3. Соединение по п. 2, где Rпредставляет собой пиридин-3-ил-RR.4. Соединени
Claims (53)
1. Соединение или его фармацевтически приемлемая соль, имеющее структуру, представленную формулой I
где R1 представляет собой гетероарил-R3R4;
R2 выбирают из группы, состоящей из Н, гетероарил-R5, гетероциклил-R6 и арил-R7;
R3 выбирают из группы, состоящей из Н, гетероциклил-R8, -NHC(=O)R9, -NHSO2R10, -NR11R12 и (С1-6-алкил)NR11R12;
при условии, что R2 и R3 не являются оба Н;
R4 представляет собой 1-3 заместителя, выбранные, каждый, из группы, состоящей из Н, С1-9-алкила, галогенида, -CF3, -CN, -OR13 и амино;
каждый R5 представляет собой независимо 1-4 заместителя, выбранные, каждый, из группы, состоящей из Н, С1-9-алкила, галогенида, -CF3, -CN, -OR13, -С(=O)R11, амино и (С1-6-алкил)NR11R12;
каждый R6 представляет собой независимо 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С1-9-алкила, галогенида, CF3, CN, OR13 и амино;
каждый R7 представляет собой независимо 1-5 заместителей,
выбранных, каждый, из группы, включающей Н, С1-9-алкил, галогенид, -CF3, -CN, -OR13, амино, (С1-6-алкил)NHSO2R11, -NR12(С1-6-алкил)NR11R12 и (С1-6-алкил)NR11R12;
R8 представляет собой 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С1-9-алкила, галогенида, -CF3, -CN, -OR13 и амино;
R9 выбирают из группы, состоящей из С1-9-алкила, гетероарил-R5, гетероциклил-R6, арил-R7 и СН2-карбоциклила;
R10 выбирают из группы, состоящей из С1-9-алкила, гетероарил-R5, гетероциклил-R6, арил-R7 и карбоциклил-R14;
каждый R11 выбирают независимо из С1-6-алкила;
каждый R12 выбирают независимо из группы, состоящей из Н и С1-6-алкила;
каждые R11 и R12 необязательно соединены с образованием пяти- или шестичленного гетероциклила;
каждый R13 выбирают независимо из группы, состоящей из Н и С1-6-алкила;
R14 представляет собой 1-5 заместителей, выбранных, каждый, из группы, состоящей из Н, С1-9-алкила, галогенида, -CF3, -CN, -OR13 и амино;
при условии, что формула I не является структурой, выбранной из группы, состоящей из:
2. Соединение по п. 1, где R1 представляет собой пиридин-R3R4.
3. Соединение по п. 2, где R1 представляет собой пиридин-3-ил-R3R4.
4. Соединение по п. 3, где R3 представляет собой (С1-6-алкил)NR11R12.
5. Соединение по п. 4, где R3 представляет собой (С1-2-алкил)NR11R12, R11 представляет собой (С1-2-алкил), R12 представляет собой (С1-2-алкил), и R4 представляет собой Н.
6. Соединение по п. 4, где R11 и R12 необязательно соединены с образованием пяти- или шестичленного гетероциклила, и R4 представляет собой Н.
7. Соединение по п. 6, где пяти- или шестичленный гетероциклил замещен 1-2 атомами фтора.
8. Соединение по п. 3, где R3 представляет собой NHC(=O)R9.
9. Соединение по п. 8, где R4 представляет собой Н, и R9 выбирают из группы, состоящей из (С2-5-алкила), фенила, карбоциклила и СН2-карбоциклила.
10. Соединение по п. 3, где R3 представляет собой -NHSO2R10.
11. Соединение по п. 10, где R4 представляет собой Н, и R10 выбирают из группы, состоящей из (С1-4-алкила) и фенила.
12. Соединение по п. 3, где R3 представляет собой гетероциклил-R8.
13. Соединение по п. 12, где R4 представляет собой Н, и гетероциклил выбирают из группы, состоящей из морфолина, пиперазина и пиперидина.
14. Соединение по п. 3, где R3 представляет собой Н, и R4 представляет собой амино.
15. Соединение по любому из пп. 3-14, в котором R2 представляет собой гетероарил-R5.
16. Соединение по любому из пп. 3-14, в котором R2 представляет собой пиридин-3-ил-R5.
17. Соединение по любому из пп. 3-14, в котором R2 представляет собой пиридин-3-ил-R5, и R5 представляет собой 1-2 атома фтора.
18. Соединение по любому из пп. 3-14, в котором R2 представляет собой тиофен-R5.
19. Соединение по любому из пп. 3-14, в котором R2 представляет собой гетероциклил-R6.
20. Соединение по любому из пп. 3-14, в котором R2 представляет собой гетероциклил-R6, при этом R6 выбирают из группы, состоящей из Н, F и (С1-4-алкила), и гетероциклил выбирают из группы, состоящей из морфолина, пиперазина и пиперидина.
21. Соединение по любому из пп. 3-14, в котором R2 представляет собой арил-R7.
22. Соединение по любому из пп. 3-14, в котором R2 представляет собой фенил-R7, и R7 представляет собой 1-2 атома фтора.
23. Соединение по любому из пп. 3-14, в котором R2 представляет собой фенил-R7, и R7 представляет собой 2 заместителя, состоящих из 1 атома фтора и или NR12(С1-6-алкил)NR11R12 или (С1-6-алкил)NHSO2R11.
24. Соединение по п. 1, имеющее структуру, выбранную из группы, состоящей из:
25. Соединение по п. 1, имеющее структуру, выбранную из группы, состоящей из:
26. Соединение по п. 1, имеющее структуру, выбранную из группы, состоящей из:
27. Фармацевтическая композиция, включающая терапевтически эффективное количество соединения по п. 1 или его фармацевтически приемлемой соли и фармацевтически приемлемый эксципиент.
28. Способ лечения расстройства или заболевания у пациента, в которое вовлечена Wnt-сигнализация, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
29. Способ по п. 28, где расстройство или заболевание представляет собой рак.
30. Способ по п. 28, где расстройство или заболевание представляет собой диабетическую ретинопатию.
31. Способ по п. 28, где расстройство или заболевание представляет собой фиброз легких.
32. Способ по п. 28, где расстройство или заболевание представляет собой ревматоидный артрит.
33. Способ по п. 28, где расстройство или заболевание представляет собой склеродермию.
34. Способ по п. 28, где расстройство или заболевание представляет собой грибковую или вирусную инфекцию.
35. Способ по п. 28, где расстройство или заболевание представляет собой болезнь костей или хрящей.
36. Способ по п. 28, где расстройство или заболевание представляет собой болезнь Альцгеймера.
37. Способ по п. 28, где расстройство или заболевание представляет собой остеоартрит.
38. Способ по п. 28, где расстройство или заболевание представляет собой болезнь легких.
39. Способ по п. 28, где расстройство или заболевание представляет собой генетическое заболевание, вызванное мутациями в компонентах Wnt-сигнализации, при этом генетическое заболевание выбирают из коли-полипоза, синдрома остеопороза-псевдоглиомы, семейной экссудативной витреоретинопатии, ретинального ангиогенеза, начальной коронарной болезни, синдрома Тетра-Амелия, регрессии и вирилизации Мюллерова протока, синдрома SERKAL, сахарного диабета 2 типа, синдрома Фурмана, синдрома фокомелии Аль-Авади/Рааса-Ротшильда/Шинцеля, одонто-ониходермальной дисплазии, ожирения, мальформации расщепленной кисти/стопы, синдрома дупликации хвостовой части, агенезии зубов, опухоли Вильмса, дисплазии скелета, очаговой дермальной гипоплазии, аутосомно-рециссивной анонихии, дефектов нервной трубки, синдрома альфа-талассемии (ARTX), синдрома ломкой Х хромосомы, синдрома ICF, синдрома Ангельмана, синдрома Прадера-Вилли, синдрома Беквита-Видемана и синдрома Ретта.
40. Способ по п. 28, где пациентом является человек.
41. Способ по п. 29, где рак выбирают из гепатоцеллюлярной карциномы, рака толстой кишки, рака молочной железы, панкреатического рака, лейкоза, лимфомы, саркомы и рака яичников.
42. Способ по п. 28, где соединение ингибирует один или несколько белков на пути Wnt.
43. Способ по п. 28, где соединение ингибирует сигнализацию, индуцированную одним или несколькими белками Wnt.
44. Способ по любому из п. 42 или 43, где белки Wnt выбирают из WNT1, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11 и WNT16.
45. Способ по п. 28, где соединение ингибирует киназную активность.
46. Способ лечения у пациента заболевания или расстройства, опосредуемого путем Wnt, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
47. Способ по п. 44, где соединение ингибирует один или несколько белков Wnt.
48. Способ лечения у пациента заболевания или расстройства, опосредуемого киназной активностью, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
49. Способ по п. 46, где заболевание или расстройство включает рост опухоли, клеточную пролиферацию или ангиогенез.
50. Способ ингибирования активности протеинкиназного рецептора, включающий контактирование рецептора с эффективным количеством соединения по п. 1 или его фармацевтически приемлемой соли.
51. Способ лечения у пациента заболевания или расстройства, ассоциированного с аберрантной клеточной пролиферацией, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
52. Способ предупреждения или уменьшения ангиогенеза у пациента, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
53. Способ предупреждения или уменьшения анормальной клеточной пролиферации у пациента, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
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Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105037355B (zh) | 2009-08-10 | 2017-06-06 | 萨穆梅德有限公司 | Wnt信号传导途径的吲唑抑制剂及其治疗用途 |
| SI3001903T1 (en) | 2009-12-21 | 2018-02-28 | Samumed, Llc | 1h-pyrazolo(3,4-b)pyridines and therapeutic uses thereof |
| CN103929963A (zh) | 2011-09-14 | 2014-07-16 | 萨穆梅德有限公司 | 吲唑-3-羧酰胺及其作为WNT/β-CATENIN信号传导通路抑制剂的用途 |
| PH12017500997A1 (en) * | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
| MY173049A (en) | 2012-05-04 | 2019-12-20 | Samumed Llc | 1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| EP2943198B1 (en) | 2013-01-08 | 2019-07-17 | Samumed, LLC | 3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof |
| GB201322334D0 (en) * | 2013-12-17 | 2014-01-29 | Agency Science Tech & Res | Maleimide derivatives as modulators of WNT pathway |
| GB201322333D0 (en) | 2013-12-17 | 2014-01-29 | Agency Science Tech & Res | WNT pathway modulators |
| CA2942687A1 (en) | 2014-03-20 | 2015-09-24 | Samumed, Llc | 5-substituted indazole-3-carboxamides and preparation and use thereof |
| EP3122739B1 (en) * | 2014-03-27 | 2019-01-16 | Merck Patent GmbH | Pyridyl piperidines |
| RU2017103289A (ru) | 2014-07-11 | 2018-08-14 | Дженентек, Инк. | Ингибирование пути notch |
| WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
| WO2016040180A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
| WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040188A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040182A1 (en) * | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof |
| WO2016040193A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
| AU2016279474B2 (en) | 2015-06-16 | 2021-09-09 | Eisai R&D Management Co., Ltd. | Anticancer agent |
| CA2986999C (en) | 2015-06-23 | 2023-08-08 | Eisai R&D Management Co., Ltd. | Crystal of (6s,9as)-n-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2h-pyrazino[2,1-c][1,2,4]triazine-1(6h)-carboxamide |
| US10285983B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-B] pyridines and therapeutic uses thereof |
| US10226448B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-yl)-1H-pyrazolo[3,4-B]pyridines and therapeutic uses thereof |
| US10392383B2 (en) | 2015-08-03 | 2019-08-27 | Samumed, Llc | 3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10226453B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| US10383861B2 (en) | 2015-08-03 | 2019-08-20 | Sammumed, LLC | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| US10206908B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| US10206909B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| WO2017024021A1 (en) * | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| US10285982B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| WO2017024015A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10195185B2 (en) | 2015-08-03 | 2019-02-05 | Samumed, Llc | 3-(1H-imidazo[4,5-C]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| WO2017024003A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| WO2017023986A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-indol-2-yl)-1h-indazoles and therapeutic uses thereof |
| US10166218B2 (en) | 2015-08-03 | 2019-01-01 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| WO2017024010A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| WO2017024025A1 (en) | 2015-08-03 | 2017-02-09 | Sunil Kumar Kc | 3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10188634B2 (en) | 2015-08-03 | 2019-01-29 | Samumed, Llc | 3-(3H-imidazo[4,5-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| CN105254613A (zh) * | 2015-10-08 | 2016-01-20 | 苏州云轩医药科技有限公司 | 具有Wnt信号通路抑制活性的杂环化合物及其应用 |
| KR102698411B1 (ko) * | 2015-10-08 | 2024-08-26 | 쑤저우 운씨엔 이야오 커지 요씨엔 공시 | Wnt 신호 전달 경로 억제제 및 이의 치료적 적용 |
| WO2017062688A1 (en) * | 2015-10-08 | 2017-04-13 | Suzhou Yunxuan Yiyao Keji Youxian Gongsi | Wnt signaling pathway inhibitors and therapeutic applications thereof |
| TWI710560B (zh) | 2015-11-03 | 2020-11-21 | 美商施萬生物製藥研發Ｉｐ有限責任公司 | 用於治療呼吸疾病之jak激酶抑制劑化合物 |
| MX389958B (es) * | 2015-11-06 | 2025-03-20 | Samumed Llc | 2- (1h-indazol-3-il) -3h-imidazo[4,5-c] piridinas y usos antiinflamatorios de las mismas. |
| MY199242A (en) * | 2016-06-01 | 2023-10-22 | Samumed Llc | Process for preparing n-(5-(3-(7-(3-fluorophenyl)-3h-imidazo[4,5-c]pyridin-2-yl)-1h-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide |
| WO2018075858A1 (en) | 2016-10-21 | 2018-04-26 | Samumed, Llc | Methods of using indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors |
| KR102558716B1 (ko) * | 2016-11-07 | 2023-07-21 | 사뮤메드, 엘엘씨 | 단일-투여량, 즉시-사용가능한 주사용 제제 |
| CN110072528B (zh) | 2017-02-08 | 2022-04-26 | 卫材R&D管理有限公司 | 治疗肿瘤的药物组合物 |
| MX388748B (es) | 2017-05-01 | 2025-03-20 | Theravance Biopharma R&D Ip Llc | Métodos de tratamiento mediante el uso de un compuesto inhibidor de jak. |
| KR20200013644A (ko) | 2017-05-16 | 2020-02-07 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 간세포 암종의 치료 |
| AR112834A1 (es) * | 2017-09-26 | 2019-12-18 | Novartis Ag | Derivados de rapamicina |
| CN108314721B (zh) * | 2018-01-25 | 2021-06-22 | 首都医科大学 | 人Wnt5a-NL核酸重组体及其制备方法与应用 |
| CN112020501A (zh) | 2018-02-23 | 2020-12-01 | 萨穆梅德有限公司 | 5-杂芳基取代的吲唑-3-基甲酰胺类及其制备和用途 |
| US10759799B2 (en) | 2018-06-15 | 2020-09-01 | Samumed, Llc | Indazole containing macrocycles and therapeutic uses thereof |
| WO2020150552A2 (en) | 2019-01-17 | 2020-07-23 | Samumed, Llc | Methods of treating cartilage disorders through inhibition of clk and dyrk |
| WO2021121420A1 (zh) * | 2019-12-20 | 2021-06-24 | 江苏凯迪恩医药科技有限公司 | 苯并吡唑类化合物及其中间体、制备方法和应用 |
| WO2022012058A1 (zh) * | 2020-07-16 | 2022-01-20 | 江苏凯迪恩医药科技有限公司 | 稠环化合物及其中间体、制备方法和应用 |
| EP4229057A1 (en) | 2020-10-13 | 2023-08-23 | Teva Czech Industries s.r.o. | Solid state forms of lorecivivint |
| US20240279201A1 (en) * | 2021-06-01 | 2024-08-22 | Fengtian Xue | Dual wnt signaling pathway inhibitors and ampk activators for treatments of disease |
| JP2024524214A (ja) | 2021-06-25 | 2024-07-05 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｊａｋ阻害剤としてのイミダゾロインダゾール化合物 |
| CN114259565A (zh) * | 2021-12-28 | 2022-04-01 | 广州市妇女儿童医疗中心 | Wnt4在制备治疗纤维化药物中的应用 |
| CN115353508B (zh) * | 2022-08-24 | 2023-07-21 | 中国药科大学 | 5-吡啶-1h-吲唑类化合物、药物组合物和应用 |
| KR20240148680A (ko) * | 2023-04-04 | 2024-10-11 | 주식회사 펠레메드 | 신규한 이미다졸 유도체 및 이의 용도 |
Family Cites Families (175)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4164559A (en) | 1977-09-21 | 1979-08-14 | Cornell Research Foundation, Inc. | Collagen drug delivery device |
| ES517193A0 (es) | 1981-11-10 | 1983-12-01 | Wellcome Found | Un procedimiento para la preparacion de nuevos derivados de imidazo (4,5-c)piridina. |
| US4474752A (en) | 1983-05-16 | 1984-10-02 | Merck & Co., Inc. | Drug delivery system utilizing thermosetting gels |
| US4783443A (en) | 1986-03-03 | 1988-11-08 | The University Of Chicago | Amino acyl cephalosporin derivatives |
| EP0410509A1 (en) | 1989-07-25 | 1991-01-30 | Duphar International Research B.V | New substituted 1H-indazole-3-carboxamides |
| GB9414139D0 (en) | 1994-07-13 | 1994-08-31 | Smithkline Beecham Plc | Novel compounds |
| US6440102B1 (en) | 1998-07-23 | 2002-08-27 | Durect Corporation | Fluid transfer and diagnostic system for treating the inner ear |
| DE19853299C2 (de) | 1998-11-19 | 2003-04-03 | Thomas Lenarz | Katheter zur Applikation von Medikamenten in Flüssigkeitsräumen des menschlichen Innenohrs |
| US6120484A (en) | 1999-02-17 | 2000-09-19 | Silverstein; Herbert | Otological implant for delivery of medicament and method of using same |
| KR100666514B1 (ko) | 1999-05-21 | 2007-02-28 | 브리스톨-마이어즈 스퀴브 컴페니 | 키나제의 피롤로트리아진 저해제 |
| DE50010931D1 (de) | 1999-06-23 | 2005-09-15 | Aventis Pharma Gmbh | Substituierte benzimidazole |
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| US6844367B1 (en) | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US6967023B1 (en) | 2000-01-10 | 2005-11-22 | Foamix, Ltd. | Pharmaceutical and cosmetic carrier or composition for topical application |
| YU54202A (sh) | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| US6897231B2 (en) | 2000-07-31 | 2005-05-24 | Signal Pharmaceuticals, Inc. | Indazole derivatives as JNK inhibitors and compositions and methods related thereto |
| US20050009876A1 (en) | 2000-07-31 | 2005-01-13 | Bhagwat Shripad S. | Indazole compounds, compositions thereof and methods of treatment therewith |
| ES2242771T5 (es) | 2000-09-15 | 2011-10-14 | Vertex Pharmaceuticals Incorporated | Compuestos de pirazol útiles como inhibidores de proteína quinasas. |
| WO2002050073A1 (en) | 2000-12-19 | 2002-06-27 | Smithkline Beecham P.L.C. | Pyrazolo[3,4-c]pyridines as gsk-3 inhibitors |
| US20050192262A1 (en) | 2001-03-13 | 2005-09-01 | Tomas Hagstrom | Treatment of tumours |
| CA2444882A1 (en) | 2001-04-30 | 2002-11-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of gsk-3 and crystal structures of gsk-3.beta. protein and protein complexes |
| GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| JP2004536113A (ja) | 2001-07-03 | 2004-12-02 | カイロン コーポレイション | チロシンキナーゼおよびセリン／スレオニンキナーゼのインヒビターとしてのインダゾールベンズイミダゾール化合物 |
| US7642278B2 (en) | 2001-07-03 | 2010-01-05 | Novartis Vaccines And Diagnostics, Inc. | Indazole benzimidazole compounds |
| US20030199516A1 (en) | 2001-09-13 | 2003-10-23 | Genesoft, Inc. | Methods of treating infection by drug resistant bacteria |
| US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6648873B2 (en) | 2001-09-21 | 2003-11-18 | Durect Corp. | Aural catheter system including anchor balloon and balloon inflation device |
| US6897208B2 (en) | 2001-10-26 | 2005-05-24 | Aventis Pharmaceuticals Inc. | Benzimidazoles |
| CA2464333C (en) | 2001-10-26 | 2011-07-26 | University Of Connecticut | Heteroindanes: a new class of potent cannabimimetic ligands |
| IL161576A0 (en) | 2001-10-26 | 2004-09-27 | Aventis Pharma Inc | Benzimidazoles and analogues and their use as protein kinases inhibitors |
| FR2831536A1 (fr) | 2001-10-26 | 2003-05-02 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de kdr |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| JP2005529850A (ja) | 2002-02-19 | 2005-10-06 | ファルマシア・イタリア・エス・ピー・エー | 三環系ピラゾール誘導体、その製造方法および抗腫瘍剤としてのその使用 |
| WO2003070706A1 (en) | 2002-02-19 | 2003-08-28 | Pharmacia Corporation | Tricyclic pyrazole derivatives for the treatment of inflammation |
| EP1506176B1 (en) | 2002-05-17 | 2013-04-24 | Pfizer Italia S.r.l. | Aminoindazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| IL164209A0 (en) | 2002-05-31 | 2005-12-18 | Eisai Co Ltd | Pyrazole derivatives and pharmaceutical compositions containing the same |
| US7449488B2 (en) | 2002-06-04 | 2008-11-11 | Schering Corporation | Pyrazolopyrimidines as protein kinase inhibitors |
| WO2003101993A1 (en) | 2002-06-04 | 2003-12-11 | Neogenesis Pharmaceuticals, Inc. | Pyrazolo` 1,5a! pyrimidine compounds as antiviral agents |
| US20050282733A1 (en) | 2002-06-27 | 2005-12-22 | Prins Johannes B | Differentiation modulating agents and uses therefor |
| GB0218625D0 (en) | 2002-08-10 | 2002-09-18 | Astex Technology Ltd | Pharmaceutical compounds |
| FR2845382A1 (fr) | 2002-10-02 | 2004-04-09 | Sanofi Synthelabo | Derives d'indazolecarboxamides, leur preparation et leur utilisation en therapeutique |
| SI1611131T1 (sl) | 2003-02-27 | 2011-03-31 | Palau Pharma Sa | Pirazolopiridinski derivati |
| US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
| WO2005012301A1 (en) | 2003-07-03 | 2005-02-10 | Aventis Pharmaceuticals Inc. | Pyrazoloisoquinoline derivatives as kinase inhibitors |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| BRPI0412259B1 (pt) | 2003-07-22 | 2019-08-20 | Astex Therapeutics Limited | Compostos de 1H-pirazol 3,4-dissubstituídos como moduladores de quinases dependentes de ciclina (CDK), seus usos, processo para a preparação dos mesmos e composição farmacêutica |
| GT200400136A (es) | 2003-07-30 | 2005-05-02 | Compuestos de indazol 3,5-disustituidos, composiciones farmaceuticas y metodos para intervenir en o inhibirlaproliferacion celular. | |
| US7008953B2 (en) | 2003-07-30 | 2006-03-07 | Agouron Pharmaceuticals, Inc. | 3, 5 Disubstituted indazole compounds, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
| US20050090529A1 (en) | 2003-07-31 | 2005-04-28 | Pfizer Inc | 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
| WO2005014554A1 (en) | 2003-08-08 | 2005-02-17 | Astex Therapeutics Limited | 1h-indazole-3-carboxamide compounds as mapkap kinase modulators |
| DK1692113T3 (en) | 2003-11-14 | 2018-01-08 | Lorus Therapeutics Inc | ARYLIMIDAZOLES AND USE THEREOF AS ANTICANCES |
| EP1532980A1 (en) | 2003-11-24 | 2005-05-25 | Novo Nordisk A/S | N-heteroaryl indole carboxamides and analogues thereof, for use as glucokinase activators in the treatment of diabetes |
| FR2864084B1 (fr) | 2003-12-17 | 2006-02-10 | Aventis Pharma Sa | Nouveaux derives organophosphores des indazoles et leur utilisation comme medicaments |
| FR2867778B1 (fr) | 2004-03-16 | 2006-06-09 | Sanofi Synthelabo | Utilisation de derives d'indazolecarboxamides pour la preparation d'un medicament destine au traitement et a la prevention du paludisme |
| EP1735306A2 (en) | 2004-03-25 | 2006-12-27 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| US7488737B2 (en) | 2004-04-22 | 2009-02-10 | Memory Pharmaceutical Corporation | Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof |
| WO2005110410A2 (en) | 2004-05-14 | 2005-11-24 | Abbott Laboratories | Kinase inhibitors as therapeutic agents |
| EP1781653A1 (en) | 2004-07-05 | 2007-05-09 | Astex Therapeutics Limited | 3,4-disubstituted pyrazoles as cyclin dependent kinases (cdk) or aurora kinase or glycogen synthase 3 (gsk-3) inhibitors |
| EP1778687A2 (en) | 2004-07-27 | 2007-05-02 | SGX Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| US7626021B2 (en) | 2004-07-27 | 2009-12-01 | Sgx Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| TW200618800A (en) | 2004-08-03 | 2006-06-16 | Uriach Y Compania S A J | Heterocyclic compounds |
| WO2006024945A1 (en) | 2004-09-03 | 2006-03-09 | Pfizer Inc. | Pharmaceutical compositions comprising a cdk inhibitor |
| US7652043B2 (en) | 2004-09-29 | 2010-01-26 | The Johns Hopkins University | WNT pathway antagonists |
| US20060116519A1 (en) | 2004-11-17 | 2006-06-01 | Agouron Pharmaceuticals, Inc. | Synthesis of 5-bromo-4-methyl-pyridin-3-ylmethyl)-ethyl-carbamic acid tert-butyl ester |
| WO2006054143A1 (en) | 2004-11-17 | 2006-05-26 | Pfizer Inc. | Polymorphs of {5-[3-(4,6-difluoro-1h-benzoimidazol-2-yl)-1h-indazol-5-yl]-4-methyl-pyridin-3-ylmethyl}-ethyl-amine |
| WO2006063302A2 (en) | 2004-12-10 | 2006-06-15 | Wyeth | Variants of glycogen synthase kinase 3 and uses thereof |
| US20060142247A1 (en) | 2004-12-17 | 2006-06-29 | Guy Georges | Tricyclic heterocycles |
| EP1833819A1 (en) | 2004-12-30 | 2007-09-19 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of cdk, gsk and aurora kinases |
| WO2008007113A2 (en) | 2006-07-14 | 2008-01-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| US20060264897A1 (en) | 2005-01-24 | 2006-11-23 | Neurosystec Corporation | Apparatus and method for delivering therapeutic and/or other agents to the inner ear and to other tissues |
| US7541367B2 (en) | 2005-05-31 | 2009-06-02 | Janssen Pharmaceutica, N.V. | 3-benzoimidazolyl-pyrazolopyridines useful in treating kinase disorders |
| WO2007023111A2 (en) | 2005-08-25 | 2007-03-01 | F. Hoffmann-La Roche Ag | P38 map kinase inhibitors and methods for using the same |
| US8106066B2 (en) | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| UY29825A1 (es) | 2005-10-03 | 2007-05-31 | Astrazeneca Ab | Derivados sustituidos de 3h-imidazol-(4,5 b (beta))piridina-2-il benzoatos y benzamidas, composiciones farmacéuticas que los contienen y aplicaciones |
| TW200804338A (en) | 2005-11-24 | 2008-01-16 | Astrazeneca Ab | New compounds |
| US8399442B2 (en) | 2005-12-30 | 2013-03-19 | Astex Therapeutics Limited | Pharmaceutical compounds |
| GB0602178D0 (en) | 2006-02-03 | 2006-03-15 | Merck Sharp & Dohme | Therapeutic treatment |
| BRPI0709082A2 (pt) | 2006-03-23 | 2011-06-28 | Hoffmann La Roche | derivados de indazol substituìdos, sua fabricação e uso como agentes farmacêuticos |
| JP5255559B2 (ja) | 2006-03-31 | 2013-08-07 | アボット・ラボラトリーズ | インダゾール化合物 |
| EP2044051B1 (en) | 2006-06-22 | 2010-01-27 | BIOVITRUM AB (publ) | Pyridine and pyrazine derivatives as mnk kinase inhibitors |
| WO2008048502A1 (en) | 2006-10-17 | 2008-04-24 | Janssen Pharmaceutica N.V. | Substituted pyrazole kinase inhibitors |
| WO2008061109A2 (en) | 2006-11-15 | 2008-05-22 | Forest Laboratories Holdings Limited | Indazole derivatives useful as melanin concentrating receptor ligands |
| EP1932830A1 (en) | 2006-12-11 | 2008-06-18 | The Genetics Company, Inc. | Sulfonamides and their use as a medicament |
| EP1932834B1 (en) | 2006-12-11 | 2011-04-27 | The Genetics Company, Inc. | Aromatic 1,4-DI-Carboxylamides and their use |
| ES2396160T3 (es) | 2006-12-14 | 2013-02-19 | Bayer Intellectual Property Gmbh | Derivados de DIHIDROPIRIDINA que utiliza como inhibidores de la proteina quinasa |
| EP2078020A4 (en) | 2007-04-10 | 2011-10-19 | Sgx Pharmaceuticals Inc | HETEROCYCLIC MODULATORS WITH FUSED CYCLES FOR KINASES |
| US20100137394A1 (en) | 2007-04-30 | 2010-06-03 | Grenentech, Inc. | Pyrazole inhibitors of wnt signaling |
| US8129519B2 (en) | 2007-05-10 | 2012-03-06 | Cholody Wieslaw M | Derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine and uses thereof |
| US20080287452A1 (en) | 2007-05-16 | 2008-11-20 | Wyeth | Heteroaryl/aryl pyrimidine analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
| WO2008147713A1 (en) | 2007-05-24 | 2008-12-04 | The Regents Of The University Of California | Wnt signaling inhibitors, and methods for making and using them |
| CL2008001540A1 (es) | 2007-05-29 | 2009-05-22 | Sgx Pharmaceuticals Inc | Compuestos derivados de pirrolopiridinas y pirazolopiridinas; composicion farmaceutica; y uso en el tratamiento del cancer. |
| US20090099062A1 (en) | 2007-05-31 | 2009-04-16 | Ethan Lee | Pyrvinium For The Treatment of Cancer |
| JP5451602B2 (ja) | 2007-06-08 | 2014-03-26 | アッヴィ・インコーポレイテッド | キナーゼ阻害薬としての５−ヘテロアリール置換インダゾール類 |
| US8648069B2 (en) | 2007-06-08 | 2014-02-11 | Abbvie Inc. | 5-substituted indazoles as kinase inhibitors |
| JP2011502958A (ja) | 2007-06-19 | 2011-01-27 | 武田薬品工業株式会社 | グルコキナーゼ活性化インダゾール化合物 |
| FR2917735B1 (fr) | 2007-06-21 | 2009-09-04 | Sanofi Aventis Sa | Nouveaux indazoles substitutes, leur preparation et leur utilisation en therapeutique |
| US20090069288A1 (en) | 2007-07-16 | 2009-03-12 | Breinlinger Eric C | Novel therapeutic compounds |
| US20100190736A1 (en) | 2007-08-02 | 2010-07-29 | Nerviano Medical Sciences S.R.L. | Morpholinyl anthracycline derivative combined with protein kinase inhibitors |
| RU2350271C1 (ru) | 2007-08-20 | 2009-03-27 | Федеральное государственное учреждение "Российский научный центр "Восстановительная травматология и ортопедия" имени академика Г.А. Илизарова Федерального агентства по высокотехнологичной медицинской помощи", ФГУ "РНЦ "ВТО" им. акад. Г.А. Илизарова Росмедтехнологий" | Способ лечения ранних стадий остеоартроза тазобедренного сустава |
| CA2698071A1 (en) | 2007-08-27 | 2009-03-05 | Wyeth Llc | Imidazopyridine analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
| US9259399B2 (en) | 2007-11-07 | 2016-02-16 | Cornell University | Targeting CDK4 and CDK6 in cancer therapy |
| CA2704125A1 (en) | 2007-12-19 | 2009-07-09 | Genentech, Inc. | 8-anilinoimidazopyridines and their use as anti-cancer and/or anti-inflammatory agents |
| CA2726164A1 (en) * | 2008-05-27 | 2009-12-23 | The Board Of Regents Of The University Of Texas System | Wnt protein signalling inhibitors |
| KR101061599B1 (ko) | 2008-12-05 | 2011-09-02 | 한국과학기술연구원 | 비정상 세포 성장 질환의 치료를 위한 단백질 키나아제 저해제인 신규 인다졸 유도체, 이의 약학적으로 허용가능한염 및 이를 유효성분으로 함유하는 약학적 조성물 |
| CN101440092B (zh) | 2008-12-25 | 2010-11-17 | 浙江大学 | 2-吲唑-4-氮杂吲哚-5-氨基衍生物及制备和应用 |
| WO2010107765A1 (en) | 2009-03-18 | 2010-09-23 | Schering Corporation | Bicyclic compounds as inhibitors of diacylglycerol acyltransferase |
| ES2660892T3 (es) | 2009-03-23 | 2018-03-26 | Merck Sharp & Dohme Corp. | Antagonistas del receptor P2X3 para el tratamiento del dolor |
| EP3025724B1 (en) | 2009-05-13 | 2018-07-11 | The University of North Carolina At Chapel Hill | Cyclin dependent kinase inhibitors and methods of use |
| UA110324C2 (en) | 2009-07-02 | 2015-12-25 | Genentech Inc | Jak inhibitory compounds based on pyrazolo pyrimidine |
| US20120184556A1 (en) | 2009-07-23 | 2012-07-19 | Conn P Jeffrey | Substituted enzoimidazolesulfonamides and substituted indolesulfonamides as mglur4 potentiators |
| CN105037355B (zh) | 2009-08-10 | 2017-06-06 | 萨穆梅德有限公司 | Wnt信号传导途径的吲唑抑制剂及其治疗用途 |
| WO2011019648A1 (en) | 2009-08-10 | 2011-02-17 | Epitherix, Llc | Indazoles as wnt/b-catenin signaling pathway inhibitors and therapeutic uses thereof |
| WO2011050245A1 (en) | 2009-10-23 | 2011-04-28 | Yangbo Feng | Bicyclic heteroaryls as kinase inhibitors |
| MY163791A (en) | 2009-12-21 | 2017-10-31 | Array Biopharma Inc | SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS cFMS INHIBITORS |
| SI3001903T1 (en) | 2009-12-21 | 2018-02-28 | Samumed, Llc | 1h-pyrazolo(3,4-b)pyridines and therapeutic uses thereof |
| CN102933557B (zh) | 2010-04-06 | 2016-08-03 | 彼得·麦卡勒姆癌症研究所 | 辐射防护剂化合物及方法 |
| DE102010043379A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 6-Fluor-1H-Pyrazolo[4,3-b]pyridine und ihre Verwendung |
| US20130310379A1 (en) | 2010-11-19 | 2013-11-21 | Constellation Pharmaceuticals | Modulators of methyl modifying enzymes, compositions and uses thereof |
| ME02409B (me) | 2011-01-13 | 2016-09-20 | Novartis Ag | Novi heterociklični derivati i njihova upotreba u tretmanu neuroloških poremećaja |
| US8889684B2 (en) | 2011-02-02 | 2014-11-18 | Boehringer Ingelheim International Gmbh | Azaindolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| WO2012129562A2 (en) | 2011-03-24 | 2012-09-27 | The Scripps Research Institute | Compounds and methods for inducing chondrogenesis |
| BR112013025142A2 (pt) | 2011-04-01 | 2019-09-24 | Univ Utah Res Found | análogos de 3-(1h-benzo{d}imidazol-2-il)-1h-indazol substituído como inibidores da cinase pdk1 |
| AU2012290116B2 (en) | 2011-08-02 | 2016-11-03 | Buck Institute For Research On Aging | Tropinol esters and related compounds to promote normal processing of APP |
| KR20140071361A (ko) | 2011-08-12 | 2014-06-11 | 에프. 호프만-라 로슈 아게 | 피라졸로[3,4-c]피리딘 화합물 및 사용 방법 |
| CA2843499A1 (en) | 2011-08-12 | 2013-02-21 | F. Hoffmann-La Roche Ag | Indazole compounds, compositions and methods of use |
| KR20140074912A (ko) | 2011-09-01 | 2014-06-18 | 에프. 호프만-라 로슈 아게 | 피롤로피라진 키나아제 억제제 |
| CN103929963A (zh) | 2011-09-14 | 2014-07-16 | 萨穆梅德有限公司 | 吲唑-3-羧酰胺及其作为WNT/β-CATENIN信号传导通路抑制剂的用途 |
| EP2810198B1 (en) | 2012-01-30 | 2023-07-12 | Universiteit Gent | Anti-invasive compounds |
| CA2868302A1 (en) | 2012-03-23 | 2013-09-26 | Dennis M. Brown | Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo |
| PH12017500997A1 (en) * | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
| AU2013255894A1 (en) | 2012-05-04 | 2014-11-13 | Basf Se | Substituted pyrazole-containing compounds and their use as pesticides |
| US9056874B2 (en) | 2012-05-04 | 2015-06-16 | Novartis Ag | Complement pathway modulators and uses thereof |
| MY173049A (en) | 2012-05-04 | 2019-12-20 | Samumed Llc | 1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| EP2943198B1 (en) | 2013-01-08 | 2019-07-17 | Samumed, LLC | 3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof |
| CN105188704B (zh) | 2013-01-16 | 2017-09-19 | 西格诺药品有限公司 | 被取代的吡咯并嘧啶化合物、其组合物和使用其的治疗方法 |
| US9327886B2 (en) | 2013-03-13 | 2016-05-03 | Bayer Healthcare Llc | Vial container with collar cap |
| SG11201507224RA (en) | 2013-03-14 | 2015-10-29 | Galapagos Nv | Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| FR3011239A1 (fr) | 2013-10-01 | 2015-04-03 | Univ Claude Bernard Lyon | Nouveaux derives comprenant un groupe pyrazole et un groupe indole, utiles en tant qu'inhibiteurs de la kinase gsk3 |
| CA2942687A1 (en) | 2014-03-20 | 2015-09-24 | Samumed, Llc | 5-substituted indazole-3-carboxamides and preparation and use thereof |
| WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040180A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040193A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
| WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
| US9538272B2 (en) | 2014-09-08 | 2017-01-03 | Apple Inc. | Acoustic mesh and methods of use for electronic devices |
| WO2016040182A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof |
| WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
| WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040188A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| US10188634B2 (en) | 2015-08-03 | 2019-01-29 | Samumed, Llc | 3-(3H-imidazo[4,5-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| US10206908B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| US10285983B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-B] pyridines and therapeutic uses thereof |
| WO2017023986A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-indol-2-yl)-1h-indazoles and therapeutic uses thereof |
| US20180221352A1 (en) | 2015-08-03 | 2018-08-09 | Samumed, Llc | 3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| US20180228780A1 (en) | 2015-08-03 | 2018-08-16 | Samumed, Llc | 3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| US10285982B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| WO2017024021A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| WO2017023973A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-indol-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| WO2017024010A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| US10392383B2 (en) | 2015-08-03 | 2019-08-27 | Samumed, Llc | 3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| WO2017024003A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10383861B2 (en) | 2015-08-03 | 2019-08-20 | Sammumed, LLC | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| US10166218B2 (en) | 2015-08-03 | 2019-01-01 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| US10206909B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| US10226448B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-yl)-1H-pyrazolo[3,4-B]pyridines and therapeutic uses thereof |
| US10195185B2 (en) | 2015-08-03 | 2019-02-05 | Samumed, Llc | 3-(1H-imidazo[4,5-C]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| WO2017024015A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10226453B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| MX389958B (es) | 2015-11-06 | 2025-03-20 | Samumed Llc | 2- (1h-indazol-3-il) -3h-imidazo[4,5-c] piridinas y usos antiinflamatorios de las mismas. |
| AR108325A1 (es) | 2016-04-27 | 2018-08-08 | Samumed Llc | Isoquinolin-3-il carboxamidas y preparación y uso de las mismas |
| MY199242A (en) | 2016-06-01 | 2023-10-22 | Samumed Llc | Process for preparing n-(5-(3-(7-(3-fluorophenyl)-3h-imidazo[4,5-c]pyridin-2-yl)-1h-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide |
| WO2018075858A1 (en) | 2016-10-21 | 2018-04-26 | Samumed, Llc | Methods of using indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors |
| KR102558716B1 (ko) | 2016-11-07 | 2023-07-21 | 사뮤메드, 엘엘씨 | 단일-투여량, 즉시-사용가능한 주사용 제제 |
| US20220062240A1 (en) | 2018-06-26 | 2022-03-03 | Biosplice Therapeutics, Inc. | Methods of treating cancer using a clk inhibitor |
| WO2020150552A2 (en) | 2019-01-17 | 2020-07-23 | Samumed, Llc | Methods of treating cartilage disorders through inhibition of clk and dyrk |
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