KR20180032611A - Tgf 베타 수용체 길항제 - Google Patents
Tgf 베타 수용체 길항제 Download PDFInfo
- Publication number
- KR20180032611A KR20180032611A KR1020187004934A KR20187004934A KR20180032611A KR 20180032611 A KR20180032611 A KR 20180032611A KR 1020187004934 A KR1020187004934 A KR 1020187004934A KR 20187004934 A KR20187004934 A KR 20187004934A KR 20180032611 A KR20180032611 A KR 20180032611A
- Authority
- KR
- South Korea
- Prior art keywords
- pyrrolo
- pyridin
- amino
- triazin
- amine
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
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- 238000000034 method Methods 0.000 claims abstract description 74
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- -1 Fluoro-6-methylpyridin-2-yl Chemical group 0.000 claims description 392
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 312
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 203
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 154
- 239000001257 hydrogen Substances 0.000 claims description 154
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims description 145
- 229960004979 fampridine Drugs 0.000 claims description 145
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- 235000005152 nicotinamide Nutrition 0.000 claims description 120
- 239000011570 nicotinamide Substances 0.000 claims description 120
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 110
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 70
- 125000000623 heterocyclic group Chemical group 0.000 claims description 67
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 67
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 63
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- 150000003839 salts Chemical class 0.000 claims description 54
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- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 33
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- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 15
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- KGRPHHFLPMPUBB-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazine Chemical compound C1=NC=NN2C=CC=C21 KGRPHHFLPMPUBB-UHFFFAOYSA-N 0.000 claims description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 9
- VSPXQZSDPSOPRO-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound NC1=NC=NN2C=CC=C12 VSPXQZSDPSOPRO-UHFFFAOYSA-N 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
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- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 claims description 6
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 6
- CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
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- 238000002560 therapeutic procedure Methods 0.000 claims description 5
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- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562195854P | 2015-07-23 | 2015-07-23 | |
| US62/195,854 | 2015-07-23 | ||
| PCT/US2016/043252 WO2017015425A1 (en) | 2015-07-23 | 2016-07-21 | Tgf beta receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180032611A true KR20180032611A (ko) | 2018-03-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187004934A Ceased KR20180032611A (ko) | 2015-07-23 | 2016-07-21 | Tgf 베타 수용체 길항제 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10336761B2 (enExample) |
| EP (1) | EP3325484A1 (enExample) |
| JP (1) | JP2018520201A (enExample) |
| KR (1) | KR20180032611A (enExample) |
| CN (1) | CN108026105B (enExample) |
| WO (1) | WO2017015425A1 (enExample) |
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|---|---|---|---|---|
| EP3394056B1 (en) | 2015-12-22 | 2021-04-14 | Shy Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| CA3066939A1 (en) | 2017-06-21 | 2018-12-27 | SHY Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| US10653682B2 (en) * | 2017-10-26 | 2020-05-19 | Southern Research Institute | Oxadiazoles and thiadiazoles as TGF-β inhibitors |
| US12391705B2 (en) | 2018-12-19 | 2025-08-19 | Shy Therapeutics, Llc | Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| MX2021007738A (es) | 2018-12-27 | 2021-08-05 | Nexys Therapeutics Inc | Derivados de (piridin-2-il)amina como inhibidores de tgf-beta r1 (alk5) para el tratamiento de cancer. |
| CN111825675B (zh) * | 2019-04-15 | 2023-08-01 | 武汉朗来科技发展有限公司 | Rock抑制剂及其制备方法和用途 |
| CN112694477B (zh) * | 2019-10-22 | 2024-02-06 | 四川科伦博泰生物医药股份有限公司 | 吡唑并环类化合物，包含其的药物组合物，其制备方法及其用途 |
| CN114728965B (zh) * | 2020-01-21 | 2024-05-28 | 四川科伦博泰生物医药股份有限公司 | 吡啶并杂环类化合物、其制备方法及用途 |
| CN113620956B (zh) * | 2020-05-06 | 2023-06-13 | 赛诺哈勃药业（成都）有限公司 | 转化生长因子受体拮抗剂、其制备方法和应用 |
| JP2025512935A (ja) * | 2022-04-08 | 2025-04-22 | シャイ・セラピューティクス・エルエルシー | がん、炎症性疾患、ｒａｓ病、及び線維性疾患の処置のためのｒａｓスーパーファミリータンパク質と相互作用する化合物 |
| US20260028365A1 (en) * | 2022-07-14 | 2026-01-29 | Biogen Ma Inc. | Tyrosine kinase 2 inhibitors and uses thereof |
| WO2024155837A1 (en) * | 2023-01-19 | 2024-07-25 | Skyhawk Therapeutics, Inc. | Compositions useful for modulating splicing |
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| WO2004022559A1 (en) * | 2002-09-04 | 2004-03-18 | Schering Corporation | Pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| WO2004065392A1 (en) | 2003-01-24 | 2004-08-05 | Smithkline Beecham Corporation | Condensed pyridines and pyrimidines and their use as alk-5 receptor ligands |
| WO2004087056A2 (en) * | 2003-03-28 | 2004-10-14 | Scios Inc. | BI-CYCLIC PYRIMIDINE INHIBITORS OF TGFβ |
| JP6104824B2 (ja) * | 2011-03-09 | 2017-03-29 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | ピリド［２，３−ｂ］ピラジン誘導体およびそれらの治療的使用 |
| CN103450204B (zh) * | 2012-05-31 | 2016-08-17 | 中国科学院上海药物研究所 | 吡咯[2，1-f][1，2，4]并三嗪类化合物，其制备方法及用途 |
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| EP3325484A1 (en) | 2018-05-30 |
| US20180215761A1 (en) | 2018-08-02 |
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