KR102565544B1 - 척수성 근위축증을 치료하기 위한 이미다조[1,2-a]피라진-1일-벤즈아마이드 화합물 - Google Patents
척수성 근위축증을 치료하기 위한 이미다조[1,2-a]피라진-1일-벤즈아마이드 화합물 Download PDFInfo
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- KR102565544B1 KR102565544B1 KR1020177002082A KR20177002082A KR102565544B1 KR 102565544 B1 KR102565544 B1 KR 102565544B1 KR 1020177002082 A KR1020177002082 A KR 1020177002082A KR 20177002082 A KR20177002082 A KR 20177002082A KR 102565544 B1 KR102565544 B1 KR 102565544B1
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- KR
- South Korea
- Prior art keywords
- pyrazin
- methylimidazo
- benzamide
- fluoro
- hydrogen
- Prior art date
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- 239000001257 hydrogen Substances 0.000 claims description 95
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
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- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
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- 239000003446 ligand Substances 0.000 claims description 8
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- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
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- PIAWRWGSLNIFRY-INIZCTEOSA-N 4-[(8aS)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-2-fluoro-N-(2-methylimidazo[1,2-a]pyrazin-6-yl)benzamide Chemical compound CC1=CN2C=C(NC(=O)C3=C(F)C=C(C=C3)N3CCN4CCC[C@H]4C3)N=CC2=N1 PIAWRWGSLNIFRY-INIZCTEOSA-N 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
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- 229910052736 halogen Inorganic materials 0.000 claims description 5
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- 239000008363 phosphate buffer Substances 0.000 description 1
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- 229920000768 polyamine Polymers 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
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- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
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- 230000011514 reflex Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000002356 single layer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
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- GGRWBBHCQJOQHI-GFCCVEGCSA-N tert-butyl (2R)-4-(5-carbamoyl-6-methoxypyridin-2-yl)-2-ethylpiperazine-1-carboxylate Chemical compound C(N)(=O)C=1C=CC(=NC=1OC)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)CC GGRWBBHCQJOQHI-GFCCVEGCSA-N 0.000 description 1
- BNPHQOODHLBYDI-MRXNPFEDSA-N tert-butyl (2R)-4-[4-[(2,8-dimethylimidazo[1,2-a]pyrazin-6-yl)carbamoyl]-3-fluorophenyl]-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(CCN1C(=O)OC(C)(C)C)C1=CC(F)=C(C=C1)C(=O)NC1=CN2C=C(C)N=C2C(C)=N1 BNPHQOODHLBYDI-MRXNPFEDSA-N 0.000 description 1
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- DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
- JOFHUHPQVOASBL-UHFFFAOYSA-N tert-butyl 4-(5-carbamoyl-6-methoxypyridin-2-yl)piperazine-1-carboxylate Chemical compound C(N)(=O)C=1C=CC(=NC=1OC)N1CCN(CC1)C(=O)OC(C)(C)C JOFHUHPQVOASBL-UHFFFAOYSA-N 0.000 description 1
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- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
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- UGEYAPVLXKEKMP-UHFFFAOYSA-L zinc;difluoromethanesulfinate Chemical compound FC(F)S(=O)O[Zn]OS(=O)C(F)F UGEYAPVLXKEKMP-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
- A61K31/495—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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/495—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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| EP14173935 | 2014-06-25 | ||
| EP14173935.9 | 2014-06-25 | ||
| PCT/EP2015/063894 WO2015197503A1 (en) | 2014-06-25 | 2015-06-22 | Imidazo[1,2-a]pyrazin-1yl-benzamide compounds for treating spinal muscular atrophy |
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| KR20170018076A KR20170018076A (ko) | 2017-02-15 |
| KR102565544B1 true KR102565544B1 (ko) | 2023-08-10 |
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| EP (1) | EP3160967B1 (https=) |
| JP (1) | JP6675334B2 (https=) |
| KR (1) | KR102565544B1 (https=) |
| CN (1) | CN106459067B (https=) |
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| CA (1) | CA2952895C (https=) |
| MX (1) | MX375925B (https=) |
| RU (1) | RU2725979C2 (https=) |
| WO (1) | WO2015197503A1 (https=) |
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| WO2015024876A2 (en) | 2013-08-19 | 2015-02-26 | F. Hoffmann-La Roche Ag | Screening method |
| IL294124B2 (en) | 2015-12-10 | 2024-02-01 | Ptc Therapeutics Inc | Methods for treating huntington's disease |
| US11407753B2 (en) | 2017-06-05 | 2022-08-09 | Ptc Therapeutics, Inc. | Compounds for treating Huntington's disease |
| WO2019005993A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | METHODS OF TREATING HUNTINGTON'S DISEASE |
| US11382918B2 (en) | 2017-06-28 | 2022-07-12 | Ptc Therapeutics, Inc. | Methods for treating Huntington's Disease |
| KR102740831B1 (ko) | 2017-11-14 | 2024-12-11 | 칠드런'즈 메디컬 센터 코포레이션 | 신규 이미다조피리미딘 화합물 및 그의 용도 |
| EP3710007A4 (en) | 2017-11-14 | 2021-12-15 | Children's Medical Center Corporation | USE OF IMIDAZOPYRIMIDINE TO MODULATE HUMAN IMMUNE RESPONSE |
| MX2020009957A (es) | 2018-03-27 | 2021-01-15 | Ptc Therapeutics Inc | Compuestos para el tratamiento de enfermedad de hungtinton. |
| EP3814360B8 (en) | 2018-06-27 | 2024-11-06 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| EP3814345B8 (en) | 2018-06-27 | 2024-10-30 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| BR112020026637A2 (pt) | 2018-06-27 | 2021-03-30 | Reborna Biosciences, Inc. | Agente profilático ou terapêutico para atrofia muscular espinhal |
| PL3814357T3 (pl) | 2018-06-27 | 2024-09-16 | Ptc Therapeutics, Inc. | Związki heterocykliczne i heteroarylowe do leczenia choroby huntingtona |
| MA54755A (fr) * | 2019-01-18 | 2021-11-24 | Biogen Ma Inc | Dérivés d'imidazo[1,2-a]pyridinyle servant d'inhibiteurs d'irak4 |
| WO2020231977A1 (en) | 2019-05-13 | 2020-11-19 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| WO2021007378A1 (en) | 2019-07-11 | 2021-01-14 | Ptc Therapeutics, Inc. | Compounds for use in treating huntington's disease |
| JP7736700B2 (ja) * | 2020-02-28 | 2025-09-09 | リミックス セラピューティクス インコーポレイテッド | 複素環アミド及びスプライシングを調節するためのその使用 |
| BR112022023025A2 (pt) * | 2020-05-13 | 2023-03-28 | Chdi Foundation Inc | Moduladores de htt para tratar doença de huntington |
| US20250018046A1 (en) * | 2021-07-07 | 2025-01-16 | Biogen Ma Inc | Compounds for targeting degradation of irak4 proteins |
| US12281116B2 (en) | 2021-11-17 | 2025-04-22 | Chdi Foundation, Inc. | HTT modulators for treating Huntington's disease |
| CN118748995A (zh) * | 2021-12-03 | 2024-10-08 | 亚根达医疗公司 | 5-嘧啶甲酰胺衍生物和其使用方法 |
| AR132351A1 (es) | 2023-04-13 | 2025-06-18 | Syngenta Crop Protection Ag | Derivados de imidazo[1,2-a]pirazina |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014012050A2 (en) | 2012-07-13 | 2014-01-16 | Indiana University Research & Technology Corporation | Compounds for treatment of spinal muscular atrophy |
| WO2014209841A2 (en) | 2013-06-25 | 2014-12-31 | F. Hoffmann-La Roche Ag | Compounds for treating spinal muscular atrophy |
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| WO2005085252A1 (en) * | 2004-03-04 | 2005-09-15 | Biofocus Discovery Limited | Imidazo ‘1,2-a’ pyrazine compounds which interact with protein kinases |
| MX2009013213A (es) * | 2007-06-08 | 2010-03-30 | Abbott Lab | Indazoles 5-sustituidos 5-heteroarilo como inhibidores de cinasa. |
| CA2821817A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Intellectual Property Gmbh | Substituted 6-imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| KR102057351B1 (ko) * | 2011-12-30 | 2019-12-18 | 피티씨 테라퓨틱스, 인크. | 척수성 근위축증을 치료하기 위한 화합물 |
| PE20150224A1 (es) * | 2012-05-11 | 2015-03-08 | Abbvie Inc | Inhibidores del nampt |
| GB201212513D0 (en) * | 2012-07-13 | 2012-08-29 | Ucb Pharma Sa | Therapeutic agents |
| EP2920177A1 (en) * | 2012-11-19 | 2015-09-23 | Novartis AG | Compounds and compositions for the treatment of parasitic diseases |
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2015
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2016
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014012050A2 (en) | 2012-07-13 | 2014-01-16 | Indiana University Research & Technology Corporation | Compounds for treatment of spinal muscular atrophy |
| WO2014209841A2 (en) | 2013-06-25 | 2014-12-31 | F. Hoffmann-La Roche Ag | Compounds for treating spinal muscular atrophy |
Also Published As
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